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Channel 1 Proffered Paper session
Date
19.09.2020
Time
16:20 - 18:00
Room
Channel 1
Chairs
  • Lisa A. Carey (Chapel Hill, NC, United States of America)
  • Veronique Dieras (Paris, France)
Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

LBA15 - Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC)

Presentation Number
LBA15
Lecture Time
16:20 - 16:32
Speakers
  • David W. Miles (Northwood, Middlesex, United Kingdom)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00

Abstract

Background

In the phase 3 IMpassion130 trial, combining atezo with first-line nab-paclitaxel for mTNBC showed significantly improved progression-free survival (PFS) and clinically meaningful overall survival (OS) benefit in patients with PD-L1+ mTNBC [Schmid NEJM 2018]. IMpassion131 (NCT03125902) evaluated atezo + PAC as first-line treatment for mTNBC.

Methods

Eligible patients (no prior systemic therapy or ≥12 months since [neo]adjuvant chemotherapy) were randomised 2:1 to atezo 840 mg or placebo (d 1 & 15 q28d), both with PAC 90 mg/m2 (d 1, 8 & 15 q28d) until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status (immune cell [IC] expression <1% vs ≥1% by VENTANA SP142 assay), prior taxane, liver metastases and geographic region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1+ (IC ≥1%) population, then in the intent-to-treat (ITT) population. OS and overall response rate (ORR) were secondary endpoints.

Results

Of 651 randomised patients, 45% had PD-L1+ mTNBC, 48% were taxane pretreated, 31% had de novo mTNBC and 27% liver metastases. Adding atezo to PAC did not improve PFS or OS in either the PD-L1+ or ITT populations (Table). PFS results in subgroups were consistent with primary results. PAC exposure was not compromised by the addition of atezo. Grade 5 (2% placebo vs 2% atezo) and grade 3/4 AEs (43% vs 49%) were balanced between arms and the safety profile was consistent with known risks of each study drug.

PD-L1+ ITT
Placebo + PAC (n=101) Atezo + PAC (n=191) Placebo + PAC (n=220) Atezo + PAC (n=431)
Data cut-off: 15 Nov 2019
PFS events, n (%) 64 (63) 115 (60) 155 (70) 283 (66)
Median PFS, months (95% CI) 5.7 (5.4–7.2) 6.0 (5.6–7.4) 5.6 (5.4–6.5) 5.7 (5.4–7.2)
PFS HR (95% CI) 0.82 (0.60–1.12) 0.86 (0.70–1.05)
Stratified log-rank p-value 0.20 Not formally tested
Best ORR, % (95% CI)a 55 (45–65) 63 (56–70) 47 (41–54) 54 (49–58)
Data cut-off: 19 Aug 2020
Deaths, n (%) 38 (38) 82 (43) 97 (44) 207 (48)
Median OS, months (95% CI) 28.3 (19.1–NE) 22.1 (19.2–30.5) 22.8 (17.1–28.3) 19.2 (16.8–22.5)
OS HR (95% CI) 1.12 (0.76–1.65) 1.11 (0.87–1.42)
2-year OS rate, % (95% CI) 51 (38–65) 49 (40–58) 45 (36–54) 42 (36–48)

aUnconfirmed

Conclusions

Atezo + PAC did not improve PFS or OS vs placebo + PAC. No new safety signals were seen. Potential reasons for the contrast with the benefit seen in IMpassion130 (atezo + nab-paclitaxel) need further exploration.

Clinical trial identification

NCT03125902.

Editorial acknowledgement

Jennifer Kelly (Medi-Kelsey Ltd), funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

D.W. Miles: Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genomic Health. J. Gligorov: Advisory/Consultancy, Research grant/Funding (institution): Daichi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genomic Health; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: MSD; Advisory/Consultancy: Mylan; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Onxeo; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Research grant/Funding (institution): Immunomedics. F. André: Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Lilly; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: GlaxoSmithKline. D. Cameron: Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: AstraZeneca. A. Schneeweiss: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Molecular Partner; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly. C.H. Barrios: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Research grant/Funding (institution): PharmaMar; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. B. Xu: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Daiichi-Sankyo. A.M. Wardley: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi-Sankyo; Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Athenex; Honoraria (self), Advisory/Consultancy: Gerson Lehrman Group; Honoraria (self), Advisory/Consultancy: Guidepoint Global; Honoraria (self): Coleman Expert Network; Honoraria (self): Helios; Honoraria (self): Health Care America; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Advisory/Consultancy: NAPP Pharma; Advisory/Consultancy, Research grant/Funding (institution): Accord Research; Advisory/Consultancy: Coleman Research; Leadership role, Full/Part-time employment, Medical Director: NIHR Manchester Clinical Research Facility at The Christie; Leadership role, Strategy Director: Association of Cancer Physicians; Leadership role, Committee Member: UK Breast Cancer Group; Leadership role, Committee Member: NHS England Chemotherapy Clinical Reference Group; Leadership role, Faculty: ESMO Breast cancer; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): 1G1 Therapeutics; Shareholder/Stockholder/Stock options, Officer/Board of Directors, Spouse/Financial dependant: Andrew Wardley Limited; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Manchester Cancer Academy; Shareholder/Stockholder/Stock options, Officer/Board of Directors: Outreach Research & Innovation Group Limited; Speaker Bureau/Expert testimony: Eisai; Research grant/Funding (self): NIHR. D. Kaen: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Raffo-Tecnofarma; Honoraria (self), Advisory/Consultancy: Varifarma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Lilly Oncology; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Array BioPharma Inc. L. Andrade: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Zodiac Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Janssen-Cilag; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche/Genentech; Speaker Bureau/Expert testimony: Merck Sharp Dohme; Speaker Bureau/Expert testimony: Novartis; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Regeneron. M. Reinisch: Honoraria (self), Advisory/Consultancy: Roche Pharma AG; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Hexal; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Celgene. M. Patre: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. L. Morales: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. K. Russell: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. M. Donica: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. J. O’Shaughnessy: Honoraria (self), Advisory/Consultancy: AbbVie Inc.; Honoraria (self), Advisory/Consultancy: Agendia; Honoraria (self), Advisory/Consultancy: Amgen Biotechnology; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Celgene Corporation; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Genentech; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: GRAIL; Honoraria (self), Advisory/Consultancy: Immunomedics; Honoraria (self), Advisory/Consultancy: Heron Therapeutics; Honoraria (self), Advisory/Consultancy: Ipsen Biopharmaceuticals; Honoraria (self), Advisory/Consultancy: Jounce Therapeutics; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Myriad; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Ondonate Therapeutics; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Puma Biotechnology; Honoraria (self), Advisory/Consultancy: Prime Oncology; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Syndax Pharmaceuticals; Honoraria (self), Advisory/Consultancy: Takeda. All other authors have declared no conflicts of interest.

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Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

LBA16 - IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer

Presentation Number
LBA16
Lecture Time
16:32 - 16:44
Speakers
  • Leisha A. Emens (Pittsburgh, United States of America)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00

Abstract

Background

Based on findings from IMpassion130, international guidelines now recommend atezolizumab (A) + nab-paclitaxel (nP) for patients (pts) with locally advanced or metastatic TNBC (mTNBC) whose tumours express PD-L1 on tumour-infiltrating immune cells (IC). Here we report prespecified final OS and long-term safety results.

Methods

The study design and final PFS analysis have been reported (Schmid NEJM 2018). Pts were randomised 1:1 to A + nP or placebo (P) + nP. Co-primary endpoints were PFS (tested in parallel in ITT and PD-L1+ pts) and OS (tested hierarchically in ITT and, if significant, in PD-L1+ pts).

Results

As of 14 April 2020, 666/902 pts (73.8%) had died; median OS follow-up was 18.8 mo (IQR, 8.9-34.7 mo). 6% of pts in the A + nP arm and 2% in the P + nP arm remained on any treatment. OS data are in the Table. 460 A + nP arm pts and 430 P + nP arm pts were safety evaluable, of whom 8% and 3%, respectively, received nP for up to 24 mo. Similarly, 5% in the A + nP arm received nP for ≥ 24 mo (vs 1% in the P + nP arm). Respectively, 51% vs 43% had a G 3-4 AE; ≈ 1% per arm had a G 5 AE (no new G 5 AEs since last analysis; no patterns seen); 24% vs 19% had a serious AE, and 59% vs 42% had an AE of special interest (G 3-4 in 8% vs 5%). No confirmed or suspected COVID-19 AEs were reported. 19% in the A + nP arm and 8% in the P + nP arm had an AE leading to treatment discontinuation (most commonly due to neuropathy); in 18% and 8%, respectively, AEs led to nP discontinuation, and in 8% and 1%, AEs led to A or P discontinuation.

Conclusions

While OS differences for A + nP vs P + nP in the IMpassion130 ITT population were not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed in PD-L1+ pts (7.5-mo median OS improvement). A + nP remained safe and tolerable with longer follow-up. Results from this final and mature OS analysis are consistent with prior interim analyses.

Final OS analysis A + nP (n = 451) P + nP (n = 451)
ITT population
Events, n (%) 322 (71) 344 (76)
Median OS (95% CI), mo 21.0 (19.0, 23.4) 18.7 (16.9, 20.8)
Stratified OS HRa (95% CI); log-rank P 0.87 (0.75, 1.02); 0.0770b
3-year OS (95% CI), % 28 (24, 32) 25 (21, 29)
PD-L1+ population c (n = 185) (n = 184)
Events, n (%) 120 (65) 139 (76)
Median OS (95% CI), mo 25.4 (19.6, 30.7) 17.9 (13.6, 20.3)
Stratified OS HR (95% CI) 0.67 (0.53, 0.86)d
3-year OS (95% CI), % 36 (29, 43) 22 (16, 28)

a Stratification factors: prior taxane use, liver metastases, PD-L1 status. b Not significant c PD-L1 positivity defined as PD-L1–stained IC on ≥ 1% of the tumour area (VENTANA SP142 IHC assay) d Not formally tested per prespecified testing hierarchy.

Clinical trial identification

NCT02425891.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Ashley J. Pratt, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

L.A. Emens: Honoraria (self): AbbVie, Amgen, Celgene, Chugai, Gritstone, MedImmune, Peregrine, Shionogi, Syndax; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca, Bayer, MacroGenics, Replimune, Vaccinex; Travel/Accommodation/Expenses: Bristol Myers Squibb, Genentech/Roche, Novartis; Research grant/Funding (institution): Aduro Biotech, AstraZeneca, The Breast Cancer Research Foundation, Bristol Myers Squibb, Bolt Therapeutics, Corvus, The US Department of Defense, EMD Serono, Genentech, Maxcyte, Merck, The National Cancer Institute, The NSABP Foundation, Roche, The Transl; Licensing/Royalties: Aduro; Advisory/Consultancy: Roche. S. Adams: Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck, Amgen, BMS, Novartis, Celgene, Daiichi Sankyo. C.H. Barrios: Advisory/Consultancy: Boehringer- Ingelheim; Advisory/Consultancy: GSK; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/ Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Non-remunerated activity/ies: Bayer; Research grant/ Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Mylan; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Biomarin; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Abraxis BioScience; Research grant/Funding (institution): AB Science; Research grant/Funding (institution): Asana BioSciences; Research grant/Funding (institution): Exelixis, Research grant/Funding (institution): ImClone Systems, Research grant/Funding (institution): LEO Pharma; Research grant/Funding (institution): Millennium; Advisory/Consultancy: Merck Sharp and Dohme; Advisory/Consultancy: AstraZeneca. V.C. Dieras: Honoraria (self), Advisory/Consultancy: Roche/Genentech, Pfizer, Lilly, Novartis, Daiichi Sankyo, AstraZeneca, AbbVie, Seattle Genetics, Odonate, MSD. H. Iwata: Honoraria (self), Advisory/Consultancy: Chugai; Honoraria (self), Advisory/Consultancy: Novartis, AstraZeneca, Pfizer, Lilly, Daiichi-Sankyo, Eisai, Kyowa Kirin; Non-remunerated activity/ies: MSD, Bayer, BI, Nihon, Kayaku, Sanofi. S. Loi: Research grant/Funding (institution), Non-remunerated activity/ies: Novartis, BMS, Roche-Genentech, Merck; Research grant/Funding (institution): Puma, Eli Lilly, Pfizer; Unpaid consultant: Seattle Genetics; Unpaid consultant: Pfizer; Unpaid consultant: Novartis; Unpaid consultant: BMS; Unpaid consultant: AstraZeneca; Unpaid consultant: Roche/Genentech; Advisory/Consultancy (institution): Aduro Biotechnology. H.S. Rugo: Research grant/Funding (institution): Pfizer, Novartis, Lilly, Genentech/Roche, Merck, OBI, Eisai, Plexxikon, Immunomedics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Macrogeneics, Daiichi; Travel/Accommodation/Expenses: Puma, Mylan, Genentech/Roche, Novartis, Pfizer; Honoraria (self): Celltrion. A. Schneeweiss: Research grant/Funding (institution): Celgene, Roche, AbbVie, Molecular Partner; Advisory/Consultancy: Roche AstraZeneca; Travel/Accommodation/Expenses: Celgene, Roche, Pfizer; Honoraria (self): Roche, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly. E.P. Winer: Honoraria (self): Lilly, Genentech, Infinite MD, Carrick Therapeutics, GSK, Jounce, Genomic HEalth, Merck, Seattle Genetics; Honoraria (self), Leadership role: Leap. S. Patel: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. V. Henschel: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. A. Swat: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. M. Kaul: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. L. Molinero: Shareholder/Stockholder/Stock options, Full/Part-time employment: F. Hoffmann-La Roche. S.Y. Chui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech/Roche. P. Schmid: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant, spouse -- consulting for Genentech: Roche; Honoraria (self): Medscape; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): GI Therapeutics; Honoraria (self): Health Interactions; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Merck; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bayer; Advisory/Consultancy: EISAI; Advisory/Consultancy: Celegence; Advisory/Consultancy: Puma; Research grant/Funding (institution), Spouse/Financial dependant, spouse -- consulting for Genentech: Genentech; Research grant/Funding (institution): Oncogenex.

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Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

Invited Discussant LBA15 and LBA16

Lecture Time
16:44 - 16:54
Speakers
  • Lisa A. Carey (Chapel Hill, NC, United States of America)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00
Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

Q&A and live discussion

Lecture Time
16:54 - 17:04
Speakers
  • Lisa A. Carey (Chapel Hill, NC, United States of America)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00
Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

LBA17 - ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC)

Presentation Number
LBA17
Lecture Time
17:04 - 17:16
Speakers
  • Aditya Bardia (Boston, United States of America)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00

Abstract

Background

In pts with pretreated mTNBC, standard of care (SOC) chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (mPFS). SG (TRODELVY™) is a first-in-class antibody-drug conjugate (ADC) composed of an anti–Trop-2 antibody coupled to the active metabolite of irinotecan, SN-38, via a unique hydrolyzable linker that allows for SN-38 release intracellularly and in the tumor microenvironment (bystander effect). In a phase I/II IMMU-132-01 study, SG demonstrated 33% ORR and an mPFS of 5.5 months (mo) in pts with mTNBC with manageable safety, leading to accelerated US FDA approval of SG. The randomized phase III ASCENT study was initiated to confirm those results.

Methods

In the ASCENT study (NCT02574455), pts with mTNBC who had relapsed/refractory disease after ≥2 prior chemotherapies in the advanced/metastatic setting (prior taxane required) were randomized 1:1 to receive SG (10 mg/kg IV on d 1, 8 every 21 d) or single-agent TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. The primary endpoint was PFS measured by central review per RECIST v1.1 in the brain metastases-negative population (BMneg). Key secondary endpoints were overall survival (OS), ORR RECIST v1.1, and safety.

Results

Of 529 pts enrolled, 468 were BMneg (median age, 54 y; median prior lines, 4). SG (n=235) compared with TPC (n=233) significantly improved mPFS (5.6 vs 1.7 mo; HR, 0.41; P<0.0001) and median OS (12.1 vs 6.7 mo; HR, 0.48; P<0.0001). ORR was 35% for SG vs 5% for TPC (P<0.0001). In the safety population (pts who received ≥1 dose of study drug; n=482), key treatment-related grade ≥3 adverse events with SG (n=258) vs TPC (n=224) were neutropenia (51% vs 33%), diarrhea (10.5% vs <1%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%). No grade >3 neuropathy or interstitial lung disease, and no treatment-related deaths were reported with SG.

Conclusions

ASCENT is the first phase III study of an ADC with significant PFS and OS improvement over SOC chemotherapy in pretreated mTNBC, confirming the clinical activity and safety profile of SG monotherapy.

Clinical trial identification

NCT02574455.

Editorial acknowledgement

Editorial and writing support was provided by Shala Thomas, PhD, of Team 9 Science, funded by Immunomedics, Inc.

Legal entity responsible for the study

Immunomedics Inc.

Funding

Immunomedics Inc.

Disclosure

A. Bardia: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Radius Health; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics; Research grant/Funding (institution): Mersana; Research grant/Funding (institution): Innocin; Advisory/Consultancy: Biothernostics, Inc.; Advisory/Consultancy, Travel/Accommodation/Expenses: Spectrum Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Taiho; Advisory/Consultancy: Daiichi Pharma/AstraZeneca; Advisory/Consultancy: Puma; Advisory/Consultancy, Travel/Accommodation/Expenses: Philipps; Advisory/Consultancy: Eli Lilly. S.M. Tolaney: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Nektar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Research grant/Funding (institution): Exelixis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: NanoString; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Puma; Research grant/Funding (institution): Cyclacel; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Celldex; Honoraria (self), Advisory/Consultancy: Paxman; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Odonate; Honoraria (self): Seattle Genetics; Honoraria (self), Advisory/Consultancy: Silverback Therapeutics; Honoraria (self), Advisory/Consultancy: G1 Therapeutics; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Anthenex. D. Loirat: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self): Amgen; Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Novartis. K. Punie: Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: Mundi Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Hoffmann-La Roche; Honoraria (self): European centre for clinical research training; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Vifor Pharma; Travel/Accommodation/Expenses: PharmaMar; Research grant/Funding (self): Sanofi. M. Oliveira: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Philips Healthcare; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Piqur; Research grant/Funding (institution): Zenith Epigenetics; Travel/Accommodation/Expenses: Grunenthal Group; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: GP Pharm; Travel/Accommodation/Expenses: Eisai. H.S. Rugo: Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Novartis; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Macrogenics; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Merck; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Daiichi; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Odonate; Travel/Accommodation/Expenses, Educational meeting: Mylan; Travel/Accommodation/Expenses, Educational meeting: AstraZeneca; Advisory/Consultancy, One-time: Samsung; Advisory/Consultancy, One-time: Puma. A. Brufsky: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Agendia; Advisory/Consultancy: Celgene; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Bayer; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Biotheranostics; Advisory/Consultancy: NanoString Technologies; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy: Bioarray Therapeutics; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Myriad Pharmaceuticals; Advisory/Consultancy: Eisai; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo/Lilly. K. Kalinsky: Advisory/Consultancy, Research grant/Funding (institution): Immunomedics; Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant: Novartis; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant: Pfizer; Research grant/Funding (institution): Calithera Biosciences; Research grant/Funding (institution): Acetylon; Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Zentalis Pharmaceuticals; Research grant/Funding (institution): CytomX Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Spouse/Financial dependant: Array Biopharma. J. Cortés: Shareholder/Stockholder/Stock options: MedSIR; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Roche; Honoraria (self): Samsung; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Cellestia Biotech; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera; Advisory/Consultancy: Merus; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Erytech Pharma; Advisory/Consultancy: Polyphor; Advisory/Consultancy: Athenex; Advisory/Consultancy: Servier; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Leuko; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution): ARIAD; Research grant/Funding (institution): Baxalta GMBH/ Servier Affaires; Research grant/Funding (institution): Guardanth health; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Piqur. J. O'Shaughnessy: Honoraria (self): Abbive; Honoraria (self): Agendia; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Eisai; Honoraria (self): Genentech; Honoraria (self): Immunomedics; Honoraria (self): Jounce Therapeutics; Honoraria (self): Eli Lilly; Honoraria (self): Merck Sharpe & Dohme; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Puma Biotechnology; Honoraria (self): Roche; Honoraria (self): Seattle Genetics. V.C. Dieras: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Seattle Genetics. L.A. Carey: Research grant/Funding (institution): Innocrin Pharma; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution), Non-remunerated activity/ies: Novartis; Research grant/Funding (institution): NanoString Technologies; Licensing/Royalties, Spouse/Financial dependant: Falcon Therapeutics; Non-remunerated activity/ies: Sanofi-Aventis; Non-remunerated activity/ies: G1 Therapeutics; Non-remunerated activity/ies: Genentech/Roche; Non-remunerated activity/ies: GlaxoSmithKline. L. Gianni: Advisory/Consultancy, Travel/Accommodation/Expenses, Licensing/Royalties: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Synaffix; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: ADC Therapeutics; Advisory/Consultancy: Odonate Therapeutics; Advisory/Consultancy: Oncolytics; Advisory/Consultancy: Genenta; Advisory/Consultancy: Sandoz; Advisory/Consultancy: MetIS; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Revolution Medicine; Advisory/Consultancy, Research grant/Funding (institution): Zymeworks; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Genentech; Advisory/Consultancy: Onkaido Therapeutics; Advisory/Consultancy: Taiho Pharmaceutical; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Synthon; Advisory/Consultancy: FortySeven; Travel/Accommodation/Expenses: Chugai Pharmaceutical. M. Piccart: Honoraria (self), Research grant/Funding (self): Immunomedics; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Camel-IDS; Honoraria (self): Crescendo Biologics; Honoraria (self): Debiopharm; Honoraria (self): G1 Therapeutics; Honoraria (self), Research grant/Funding (self): Roche-Genentech; Honoraria (self): Huya; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self): Menarini; Honoraria (self), Research grant/Funding (self): Merck Sharp & Dohme; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self): Odonate; Honoraria (self): Periphagen; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self): Seattle Genetics; Research grant/Funding (self): Radius; Research grant/Funding (self): Servier; Research grant/Funding (self): Synthon. S. Loibl: Honoraria (institution), Research grant/Funding (self): AbbVie; Honoraria (institution), Research grant/Funding (self): Amgen; Honoraria (institution), Research grant/Funding (self): AstraZeneca; Honoraria (institution), Research grant/Funding (self): Celgene; Honoraria (institution), Research grant/Funding (self): Novartis; Honoraria (institution), Research grant/Funding (self): Pfizer; Honoraria (institution), Research grant/Funding (self): Roche; Honoraria (institution): Seattle Genetics; Honoraria (institution): PriME/ Medscape; Honoraria (self): Chugai; Honoraria (self): Teva; Honoraria (self): Vifor; Honoraria (institution), Research grant/Funding (self): Daiichi-Sankyo; Honoraria (institution): Eli Lilly; Honoraria (institution): Samsung; Advisory/Consultancy, Advisory fee paid to institute: Eirgenix; Advisory/Consultancy, advisory fee paid to institute: Bristol-Myers Squibb; Advisory/Consultancy, Advisory fee paid to institute: Puma; Honoraria (institution): Merck Sharp & Dohme; Research grant/Funding (self): Immunomedics; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0 pending. D. Goldenberg: Shareholder/Stockholder/Stock options, Licensing/Royalties: Immunomedics; Leadership role: Center for Molecular Medicine & Immunology. Q. Hong M.S. Olivo: Full/Part-time employment: Immunomedics. L.M. Itri: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: The Medicines Company; Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics; Spouse/Financial dependant: Memorial Sloan Kettering Cancer Institute. S.A. Hurvitz: Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Biomarin; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Marcogenics; Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Pieris; Research grant/Funding (institution): Radius; Research grant/Funding (institution): Arvinas.

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Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

LBA18 - Overall survival (os) results from SOLAR-1, a phase III study of alpelisib (ALP) + fulvestrant (FUL) for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC)

Presentation Number
LBA18
Lecture Time
17:16 - 17:28
Speakers
  • Fabrice AndrĂ© (Villejuif, France)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00

Abstract

Background

Phosphatidylinositol 3-kinase (PI3K) pathway hyperactivation due to PIK3CA mutations contributes to poor survival in patients (pts) with HR+, HER2– ABC (Mosele 2020). In the phase III SOLAR-1 trial of pts with progression on/after aromatase inhibitor (AI), the PI3Kα inhibitor ALP together with FUL significantly improved progression-free survival (PFS) in the PIK3CA-mutant (mut) cohort (HR 0.65; 95% CI 0.50-0.85; P<0.001; median [m] PFS 11.0 mo with ALP + FUL vs 5.7 mo with placebo [PBO] + FUL), a population with poor prognosis. At final PFS analysis, the first interim OS results were immature.

Methods

Men/postmenopausal women (N=572) with HR+, HER2– ABC with no prior chemotherapy treatment (tx) and whose disease progressed on/after AI were randomized 1:1 to receive ALP (300 mg PO QD) or PBO, + FUL (500 mg IM on D1 and D15 of C1 then D1 of each 28-d cycle) and stratified by presence of lung and/or liver metastases and prior cyclin-dependent kinase 4/6 inhibitor. OS in the PIK3CA-mut cohort, a key secondary endpoint, was evaluated by Kaplan-Meier methodology; a 1-sided stratified log-rank test was performed with an O’Brien-Fleming efficacy boundary of P≤0.0161.

Results

With mOS follow-up of 30.8 mo, mOS was 39.3 mo (95% CI 34.1-44.9) with ALP + FUL and 31.4 mo (95% CI 26.8-41.3) with PBO + FUL (HR 0.86; 95% CI 0.64-1.15; P=0.15); OS did not cross the prespecified boundary. Median time to chemotherapy (TTC) was 23.3 mo (95% CI 15.2-28.4) with ALP + FUL and 14.8 mo (95% CI 10.5-22.6) with PBO + FUL (HR 0.72; 95% CI 0.54-0.95). In pts with lung and/or liver metastases, mOS was 37.2 mo (95% CI 28.7-43.6) with ALP + FUL and 22.8 mo (95% 19.0-26.8) with PBO + FUL (HR 0.68; 95% CI 0.46-1.00). No new safety signals were observed with longer follow-up.

Conclusions

Though not statistically significant, OS was prolonged by a clinically relevant ≈8 mo with ALP when added to FUL in HR+, HER2−, PIK3CA-mut ABC. mTTC was also prolonged with ALP + FUL vs PBO + FUL. Coupled with the statistically and clinically significant PFS, these data further support ALP + FUL in this poorer prognostic population of pts with PIK3CA-mut ABC.

Clinical trial identification

NCT02437318.

Editorial acknowledgement

We thank Rob M. Camp, PhD, of Healthcare Consultancy Group, LLC, for his medical editorial assistance with this abstract, which was funded by Novartis Pharmaceuticals.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

F. André: Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Daiichi Sankyo. E.M. Ciruelos: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self): AstraZeneca. D. Juric: Research grant/Funding (self): Novartis; Advisory/Consultancy: Genentech; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: EMD Serono. S. Loibl: Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Celgene; Honoraria (institution), Research grant/Funding (institution): Amgen; Honoraria (institution), Research grant/Funding (institution): Roche; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): AbbVie; Honoraria (institution): Eli Lilly; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (institution): Eirgenix; Honoraria (institution): Seattle Genetics; Honoraria (institution): PriME/ Medscape; Honoraria (self): Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution): Samsung; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Puma; Honoraria (institution): MSD; Research grant/Funding (institution): Immunomedics. M. Campone: Research grant/Funding (institution), Non-remunerated activity/ies: Novartis; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Advisory/Consultancy: Servier; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Accord; Research grant/Funding (institution): Tesaro; Advisory/Consultancy: Eli Lilly. I. Mayer: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Seattle Genetics; Research grant/Funding (institution): Pfizer; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Puma. G. Rubovszky: Honoraria (self): Novartis. T. Yamashita: Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): Eisai; Honoraria (self): Novartis; Honoraria (self): Taiho; Honoraria (self), Research grant/Funding (institution): Nippon Kayaku; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Kyowa Kirin; Honoraria (self): Pfizer Japan; Honoraria (self): Eli Lilly; Honoraria (self): Daiichi Sankyo. B. Kaufman: Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): AbbVie. Y-S. Lu: Advisory/Consultancy, Speaker Bureau/Expert testimony, Clinical study trial fee: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): GlaxoSmithKline. K. Inoue: Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Parexel/Puma Biotechnology; Research grant/Funding (institution): MSD; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Sanofi. M. Takahashi: Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Nippon Kayaku; Research grant/Funding (institution): Taiho. F. Ghaznawi: Full/Part-time employment: Novartis Pharmaceuticals Corporation. D. Mills: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharma AG. M. Kaper, M. Miller: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceuticals Corporation. P.F. Conte: Speaker Bureau/Expert testimony: Genenetech/Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Merck Serono; Travel/Accommodation/Expenses: Celgene. H. Iwata: Honoraria (self), Advisory/Consultancy: Daiichi-Sankyo; Honoraria (self), Advisory/Consultancy: Chugai/Roche; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Uncompensated member of the steering committee for the SOLAR-1 trial: Novartis; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self): Eisai; Honoraria (self): Taiho; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Odonate; Advisory/Consultancy: Kyowa Hako Kirin; Honoraria (self), Advisory/Consultancy: AstraZeneca. H.S. Rugo: Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution): Odonate Therapeutics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi-Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: Macrogenics; Travel/Accommodation/Expenses: Mylan; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Immunomedics; Advisory/Consultancy: Samsung; Advisory/Consultancy: Puma; Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Sermonix; Research grant/Funding (institution): Seattle Genetics. All other authors have declared no conflicts of interest.

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Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

273O - nextMONARCH: Final overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with HR+, HER2- metastatic breast cancer

Presentation Number
273O
Lecture Time
17:28 - 17:40
Speakers
  • Erika P. Hamilton (Nashville, United States of America)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00

Abstract

Background

Abemaciclib, an oral, continuously dosed cyclin-dependent kinase 4 & 6 (CDK 4 & 6) inhibitor, improves progression free survival (PFS) in combination with endocrine therapy (ET) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (MBC) in the phase III MONARCH2 and 3 studies. In the phase II nextMONARCH study, primary analysis of PFS and ORR confirmed the robust single-agent activity of abemaciclib in heavily pretreated HR+, HER2- MBC with no significant improvement by addition of tamoxifen. We here report the final 24-month overall survival results.

Methods

nextMONARCH was a multicenter, randomized, open-label phase II trial of abemaciclib in women with heavily pretreated HR+, HER2- MBC whose disease progressed on or after ET and chemotherapy. Patients were randomized 1:1:1 to abemaciclib 150 mg + tamoxifen 20 mg (A+T), or abemaciclib 150 mg (A-150) or abemaciclib 200 mg plus prophylactic loperamide (A-200). Final OS analysis occurred 24 months after the last patient entered treatment. OS was a preplanned secondary endpoint.

Results

At the time of data cutoff (28-June-2019), 12 of the 234 patients enrolled were still ongoing on study treatment. Median follow-up was 27.2 months. Median OS was 24.2 months in the A+T arm, compared to 20.8 months in A-150, and 17.0 months in A-200 (A+T vs. A-150: HR 0.620 (95% CI [0.397, 0.969] p=0.034); A-150 vs. A-200: HR 0.956 (95% CI [0.635, 1.438] p=0.832)). The primary PFS endpoint and ORR were unchanged at the 24-month analysis. Common treatment-emergent adverse events (TEAEs) across all abemaciclib arms occurring in ≥25% of patients included diarrhea (61.1%), neutropenia (49.6%), anemia (40.6%), nausea (36.3%), leukopenia (30.8%), fatigue (29.9%) and abdominal pain (27.4%).

Conclusions

Addition of tamoxifen to abemaciclib provided a statistically significant median OS improvement compared to abemaciclib monotherapy in this heavily pretreated HR+, HER2- MBC patient population. PFS was consistent with the primary results of nextMONARCH with no significant difference. No new safety findings were observed.

Clinical trial identification

NCT02747004.

Editorial acknowledgement

Nicholas Pulliam, PhD - Eli Lily and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

E.P. Hamilton: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Fred Hutchinson; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): StemCentrx; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zymeworks; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Mersana; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): TapImmune; Research grant/Funding (institution): Cascadian; Research grant/Funding (institution): Eli Lilly and Company; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Medication; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Kamdon; Research grant/Funding (institution): BI; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): H3 Biomedicines; Research grant/Funding (institution): Radius; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Macrogenics. J. Cortés: Research grant/Funding (institution): Puma C; Honoraria (self), Advisory/Consultancy: Celgene; Advisory/Consultancy: Cellestia; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera Pharmaceutical; Advisory/Consultancy: Merus; Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Erytech; Advisory/Consultancy: Athenex; Advisory/Consultancy: Polyphor; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sharp&Dohme; Advisory/Consultancy: GSK; Advisory/Consultancy: Leuko; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Samsung Bioepis; Research grant/Funding (institution): Ariad Pharmaceuticals; Research grant/Funding (institution): Baxalta GMBH/Servier Affaires; Research grant/Funding (institution): Bayer Healthcare; Research grant/Funding (institution): Guardanth Health; Research grant/Funding (institution): Piqur Therapeutics. K. Petrakova: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): BMS. G. Jerusalem: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Puma Biotechnology. J. Huober: Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Hexal; Travel/Accommodation/Expenses: Daiichi. All other authors have declared no conflicts of interest.

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Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

Invited Discussant LBA17, LBA18 and 273O

Lecture Time
17:40 - 17:50
Speakers
  • Fatima Cardoso (Lisbon, Portugal)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00
Proffered Paper - Breast cancer, metastatic 1 Proffered Paper session

Q&A and live discussion

Lecture Time
17:50 - 18:00
Speakers
  • Lisa A. Carey (Chapel Hill, NC, United States of America)
Room
Channel 1
Date
19.09.2020
Time
16:20 - 18:00