Proffered Paper session I Proffered Paper session

68O - Electromagnetic navigation bronchoscopy in the European cohort of the prospective, multicenter NAVIGATE study

Presentation Number
68O
Lecture Time
16:30 - 16:45
Speakers
  • K. Lau (London, United Kingdom)
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
Wed, 10.04.2019
Time
16:30 - 18:15
Authors
  • K. Lau (London, United Kingdom)
  • J. Flandes (Madrid, Spain)
  • M. Christensen (Copenhagen, Denmark)
  • M. Bezzi (Firenze, Italy)
  • B. Lamprecht (Linz, Austria)
  • M. Salio (Genova, Italy)
  • J. Vergnon (St. Etienne, cédex 2, France)
  • M. Studnicka (Salzburg, Austria)
  • M. Trigiani (Firenze, Italy)
  • I. Fernandez (Madrid, Spain)
  • R. Kropfmüller (Linz, Austria)
  • E. Barisione (Genova, Italy)
  • N. Viby (Copenhagen, Denmark)
  • S. Khandhar (Falls Church, VA, United States of America)
  • E. Folch (Boston, MA, United States of America)

Abstract

Background

Electromagnetic navigation bronchoscopy (ENB) is an image-guided approach to access peripheral pulmonary lesions. ENB has been evaluated in a prospective global study (NAVIGATE, NCT02410837, Khandhar, BMC Pulm Med 2017;17:59). Practice patterns and safety specifically in the full European cohort have not yet been presented. The objective of this study is to evaluate ENB safety and usage in the NAVIGATE European sites.

Methods

NAVIGATE is a global, prospective, multicenter study of ENB (superDimension™ navigation system) use in community and academic settings. A prespecified 1-month interim analysis was conducted of the European cohort.

Results

Subjects (n = 175) were enrolled at 8 European sites, with complete 1-month follow-up in 99.4%. ENB was used to aid in lung biopsy in 99.4% (174/175) and fiducial marking in 8.0% (14/175). Lymph node sampling was attempted in 12 procedures (9 using linear EBUS). General anesthesia was used in 57%, radial EBUS in 4.0%, cone-beam CT in 9.7%, fluoroscopy in 41.7%, and rapid on-site evaluation (ROSE) in 17.9%. The median lesion size was 18.0 mm. Lesions were in the peripheral third of the lung in 72.7% and the upper lobe in 62.6%. A bronchus sign was present in 66.8%. Navigation was successful in 96.6% of biopsy cases. The median ENB planning time was 12.5 minutes. The median total procedure time (bronchoscope in to bronchoscope out) was 43.5 minutes, which included 32.9 minutes of ENB-specific navigation/sampling time (first entry to last exit of the locatable guide or extended working channel). The ENB-related pneumothorax rate was 7.4% (13/175), 5.1% requiring intervention or hospitalization. The ENB-related Common Terminology Criteria for Adverse Events Grade ≥2 bronchopulmonary hemorrhage and Grade ≥4 respiratory failures rates were 2.3% and 0.6%, respectively. Longer follow-up is required to assess diagnostic yield.

Conclusions

The results from the European cohort of the NAVIGATE study suggest that ENB provides a safe platform to aid in lung lesion biopsy. ENB also allows multidimensional lung lesion biopsy, fiducial placement, and concurrent lymph node sampling during a single anesthetic event.

Clinical trial identification

NCT02410837. First posted April 8, 2015.

Editorial acknowledgement

Medical writing support was provided by Kristin L. Hood PhD of Medtronic, in accordance with Good Publication Practice (GPP3) guidelines.

Legal entity responsible for the study

Medtronic.

Funding

Medtronic.

Disclosure

K. Lau, M. Christensen, M. Bezzi, B. Lamprecht, M. Salio, J.M. Vergnon, M. Studnicka, M. Trigiani, I. Fernandez, R. Kropfmüller, E. Barisione, N-E. Viby: Research funding to institution for participating in the Medtronic-sponsored NAVIGATE study. J. Flandes: Consulting fees, research funding to institution: Medtronic (Steering Committee, study principal investigator); Consulting fees: BTG-PneumRx, Olympus, Ambu, PulmonX, Boston Scientific; Research grant support: BTG-PneumRx. S. Khandhar: Consulting fees: Medtronic (study principal investigator and Steering Committee, clinical advisory board); Advisory board: Boston Scientific; Research funding to institution: Medtronic-sponsored NAVIGATE study; Stock ownership: TransEnterix. E. Folch: Consulting fees: Medtronic (study principal investigator, Steering Committee, clinical advisory board); Scientific advisory board: Boston Scientific.

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Proffered Paper session III Proffered Paper session

106O - Brigatinib (BRG) vs crizotinib (CRZ) in the phase III ALTA-1L trial

Presentation Number
106O
Lecture Time
09:21 - 09:33
Speakers
  • R. Califano (Manchester, United Kingdom)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Fri, 12.04.2019
Time
08:30 - 10:00
Authors
  • R. Califano (Manchester, United Kingdom)
  • M. Hochmair (Vienna, Austria)
  • C. Gridelli (Avellino, Italy)
  • A. Delmonte (Meldola, Italy)
  • M. Garcia Campelo (Coruna, Spain)
  • A. Bearz (Aviano, Italy)
  • F. Griesinger (Oldenburg, Germany)
  • A. Morabito (Naples, Italy)
  • E. Felip (Barcelona, Spain)
  • S. Ghosh (London, United Kingdom)
  • M. Tiseo (Parma, Italy)
  • J. Haney (Cambridge, MA, United States of America)
  • D. Kerstein (Cambridge, MA, United States of America)
  • S. Popat (London, United Kingdom)
  • D. Camidge (Aurora, CO, United States of America)

Abstract

Background

We report results of the first interim analysis (IA) from the ALTA-1L study of BRG vs CRZ in anaplastic lymphoma kinase (ALK) inhibitor–naive, ALK-positive non–small cell lung cancer (ALK+ NSCLC; NCT02737501).

Methods

This open-label, multicenter study enrolled patients (pts) with advanced ALK+ NSCLC. Eligible pts had ≤1 prior systemic therapy for advanced NSCLC. Asymptomatic central nervous system (CNS) metastases were allowed. Pts were randomized 1:1 to BRG 180 mg QD with 7-day lead-in at 90 mg or CRZ 250 mg BID. Primary endpoint was blinded independent review committee (BIRC)-assessed progression-free survival (PFS; RECIST v1.1); secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). IAs were planned at 50% and 75% of 198 expected PFS events.

Results

275 pts were randomized (BRG/CRZ, n = 137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cutoff (19 Feb 2018), with a median follow-up of 11.0/9.3 months (BRG/CRZ) and 99 PFS events, BRG met the prespecified threshold for statistical superiority vs CRZ in the primary endpoint of BIRC-assessed PFS (HR 0.49; 95% CI, 0.33–0.74; log-rank P = 0.0007); BRG median PFS was not reached (NR; 95% CI, NR) vs CRZ 9.8 months (95% CI, 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI, 0.30–0.68); log-rank P = 0.0001. Table shows additional efficacy data. Most common grade ≥3 treatment-emergent adverse events (AEs): BRG: increased blood creatine phosphokinase (16.2%) and lipase (13.2%), hypertension (9.6%); CRZ: increased alanine aminotransferase (9.5%), aspartate aminotransferase (5.8%), and lipase (5.1%). Any grade interstitial lung disease/pneumonitis: BRG, 3.7%; CRZ, 2.2%. Discontinuations due to AE (BRG/CRZ): 11.8%/8.8%.

Conclusions

BRG showed a statistically and clinically significant improvement in PFS vs CRZ in ALK inhibitor–naive ALK+ NSCLC.

Clinical trial identification

NCT02737501.

Editorial acknowledgement

Professional medical writing assistance was provided by Lauren Gallagher, PhD, (Peloton Advantage, Parsippany, NJ) and funded by Millennium Pharmaceuticals, Inc.

Legal entity responsible for the study

ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Funding

ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Disclosure

R. Califano: Honoraria, consulting/advisory role: AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Novartis, Pfizer, Lilly Oncology. C. Gridelli: Speakers bureau, advisory role: Pfizer, Roche. A. Delmonte: Consulting/advisory role: AstraZeneca, Boehringer Ingelheim. M.R. Garcia Campelo: Honoraria: ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim; Speakers bureau, advisory role: ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim. A. Bearz: Speakers bureau, advisory role: AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Takeda. F. Griesinger: Research funding to institution: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens; Consulting or advisory role: ARIAD, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, ARIAD, AbbVie, Siemens. E. Felip: Consulting/advisory role: AbbVie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Guardant Health, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda; Speakers bureau: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda. S. Popat: Research funding to institution: Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda; Honoraria: Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Consulting or advisory role: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, AbbVie; Travel, accommodations, expenses: Boehringer Ingelheim, BMS, Merck Sharp & Dohme. A. Morabito: Honoraria: AstraZeneca, Roche, Boehringer Ingelheim, Pfizer, MSD, BMS. S. Ghosh: Honoraria/speakers bureau: Pfizer. M. Tiseo: Speakers bureau, advisory role: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche. J. Haney, D. Kerstein: Employment, stock and other ownership interests: Arîad. D.R. Camidge: Honoraria: AstraZeneca, Takeda, Arrys/Kyn, Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Ignyta, Daichii Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med, Orion, Clovis, Celgene, Novartis); Research funding (ARIAD/Takeda). All other authors have declared no conflicts of interest.

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Proffered Paper session III Proffered Paper session

105O - Osimertinib for patients (pts) with leptomeningeal metastases (LM) associated with EGFRm advanced NSCLC: The AURA LM study

Presentation Number
105O
Lecture Time
08:54 - 09:06
Speakers
  • M. Ahn (Seoul, Korea, Republic of)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Fri, 12.04.2019
Time
08:30 - 10:00
Authors
  • M. Ahn (Seoul, Korea, Republic of)
  • C. Chiu (Taipei, Taiwan)
  • Y. Cheng (Changchun, Jilin, China)
  • J. Han (Goyang, KR, Korea, Republic of)
  • S. Goldberg (New Haven, United States of America)
  • A. Greystoke (Newcastle upon Tyne, Tyne and Wear, United Kingdom)
  • J. Crawford (Durham, NC, United States of America)
  • Y. Zhao (Zhengzhou, China)
  • X. Huang (Cambridge, United Kingdom)
  • M. Johnson (Cambridge, United Kingdom)
  • K. Vishwanathan (Waltham, United States of America)
  • A. Mendoza-Naranjo (Cambridge, United Kingdom)
  • T. Mok (Shatin, Hong Kong PRC)

Abstract

Background

Osimertinib, a 3rd-generation EGFR-TKI selective for both sensitising and EGFR T790M resistance mutations, has shown efficacy in pts with CNS metastases; encouraging activity has been reported in pts with LM at 160 mg once daily (QD) (BLOOM; NCT02228369). We report LM activity with osimertinib 80 mg QD in pts with LM from studies across the AURA program (NCT01802632; NCT02094261; NCT02442349; NCT02151981).

Methods

Pts with EGFR T790M positive advanced NSCLC and progression on EGFR-TKI received osimertinib 80 mg QD. Patients with LM and CNS metastases were eligible if asymptomatic and stable. Baseline brain scans were mandated in pts with known or treated CNS metastases at study entry; pts with evidence of LM by neuroradiological blinded independent review (BICR) were included for retrospective analysis. Follow-up brain scans were assessed for radiologic LM response by LM BICR per Response Assessment in Neuro-Oncology LM criteria. LM objective response rate (ORR), LM duration of response (DoR), LM progression-free survival (PFS) and overall survival (OS) were assessed retrospectively. Results are based on individual data cutoffs for each study. A longitudinal analysis overlaid changes from baseline non-CNS tumour size with LM responses at each visit for AURA LM and BLOOM LM pts.

Results

22 LM pts from the AURA studies were included for analysis. Median treatment exposure was 7.3 mo (range 2.3–16.5). Baseline characteristics were broadly consistent with the overall AURA study population: median age 58 yrs; female 59%; Asian 82%; WHO PS 1 82%. LM ORR was 55% (95% CI 32, 76); complete or partial LM response reported in 6 pts (27%) each. Median LM DoR was not reached (95% CI 2.8, not calculable [NC]). Median LM PFS was 11.1 mo (95% CI 4.6, NC). OS was 18.8 mo (95% CI 6.3, NC). Graphical assessment of longitudinal analysis showed similar non-CNS and LM responses in AURA LM and BLOOM LM pts.

Conclusions

Consistent with early efficacy outputs from BLOOM (160mg QD), osimertinib 80 mg QD showed a clinically meaningful benefit in pts with T790M-positive NSCLC and radiographically-detected LM. Additional studies are needed to further evaluate the CNS efficacy of osimertinib 80 mg QD in pts with EGFRm NSCLC and LM.

Clinical trial identification

AURA extension (NCT01802632), AURA2 (NCT02094261), AURA3 (NCT02151981), AURA17 (NCT02442349).

Editorial acknowledgement

Medical support was provided by Robert Harrison, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, and funded by AstraZeneca, Cambridge, UK, in accordance with Good Publications Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M-J. Ahn: Speakers’ bureau: AstraZeneca, MSD, ONO, Lilly, Roche; Consultant: Alpha Pharmaceutical. C-H. Chiu: Honorarium: AZ, BI, Novartis, Pfizer, Roche. J-Y. Han: Honoraria: Roche, AstraZeneca, BMS, MSD; Advisory role: AstraZeneca, BMS, MSD, Lilly, Novartis, Pfizer; Research fund: Roche, Pfizer, ONO. S.B. Goldberg: Research support: AstraZeneca; Advisory board member: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum. A. Greystoke: Consultancy fees, speaker fees: AstraZeneca. J. Crawford: Scientific advisor: Amgen, Enzychem, Merck, Pfizer; Consultant: Amgen, AstraZeneca, Coherus, Enzychem, Merck, Pfizer; Research support: AstraZeneca, Genentech, Helsinn; Chair/DSMB member: Beyond Spring, G1 Therapeutics, Janssen, Merrimack, Mylan, Roche. X. Huang, M. Johnson, K. Vishwanathan, A. Mendoza-Naranjo: Employee, shareholder: AstraZeneca. T.S.K. Mok: Leadership (for-profit): ChiMed, Sanomics Ltd.; Leadership (non-profit): IASLC, ASCO, Chinese Society of Clinical Oncology; Shareholder: Sanomics Ltd.; Honoraria: AZ, BI, Roche/Genentech, Pfizer, Lilly, Merck Serono, MSD, Novartis, SFJ, ACEA, Vertex, BMS, Oncogenex, Celgene, Ignyta, Cirina, Fishawack Facilitate, Takeda Oncology, Janssen, ChiMed; Consulting/advisory role: AZ, BI, Roche/Genentech, Pfizer, Lilly, Merck Serono, MSD, Novartis, SFJ Company, ACEA, Vertex, BMS, GeneDecode, Oncogenex, Celgene, Ignyta, Cirina, Fishawack Facilitate, Janssen, Takeda Oncolog, ChiMed; Research funding: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS, Eisai, Taiho, Merck Serono, XCovery. All other authors have declared no conflicts of interest.

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Proffered Paper session III Proffered Paper session

84O - Phase I study of gefitinib (G) + durvalumab (D) for locally advanced/metastatic non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) sensitising mutations

Presentation Number
84O
Lecture Time
08:30 - 08:42
Speakers
  • D. Gibbons (Houston, TX, United States of America)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Fri, 12.04.2019
Time
08:30 - 10:00
Authors
  • B. Creelan (Tampa, FL, United States of America)
  • T. Yeh (Boston, MA, United States of America)
  • S. Kim (Seoul, Korea, Republic of)
  • N. Nogami (Matsuyama City, Japan)
  • D. Kim (Seoul, Korea, Republic of)
  • L. Chow (Seattle, WA, United States of America)
  • S. Kanda (Tokyo, Japan)
  • R. Taylor (Cambridge, United Kingdom)
  • W. Tang (Gaithersburg, MD, United States of America)
  • M. Tang (Gaithersburg, MD, United States of America)
  • H. Angell (Cambridge, United Kingdom)
  • M. Roudier (Cambridge, United Kingdom)
  • M. Marotti (Cambridge, United Kingdom)
  • D. Gibbons (Houston, TX, United States of America)

Abstract

Background

G and D have both shown efficacy in patients (pts) with NSCLC; G + D may improve durability of response.

Methods

This Phase 1 dose escalation (Part A) and expansion (Part B) study (NCT0208811) assessed G 250 mg once daily + D 3 mg/kg (Part A) or 10 mg/kg (Parts A + B) every 2 weeks in pts with locally advanced/metastatic NSCLC. Part A pts were all comers who had failed to respond/relapsed following standard treatment (Tx). Part B pts had sensitising EGFR mutations and were tyrosine kinase inhibitor naïve: Arms 1 + 1a received G + D; Arm 2 received G (4 weeks) before G + D. Primary objective: safety/tolerability. Secondary objectives: pharmacokinetics (PK), pharmacodynamics, immunogenicity (anti-drug antibodies [ADAs]) and efficacy. Exploratory objective: evaluation of biomarkers (e.g. tumour programmed cell death ligand-1 [PD-L1]) and relationship with efficacy.

Results

There were no dose limiting toxicities in Part A (n = 16) and D 10 mg/kg was used in Part B. In Part B (n = 40) all pts had possible Tx related adverse events (TRAEs; Table): diarrhoea (68%) and elevated alanine aminotransferase (ALT; 58%) were the most common TRAEs; elevated ALT (20%) and aspartate aminotransferase (15%) were the most common TRAEs leading to discontinuation. PK were as expected, inhibition of soluble PD-L1 was observed in all pts and no Tx emergent ADAs were observed. In Arms 1 + 1a, most patients achieved objective response (63.3%; 95% confidence intervals [CI]: 43.9, 80.1), median duration of response was 9.2 months (95% CI: 3.7, 14.0) and median progression-free survival (mPFS) was 10.1 months (95% CI: 5.5, 15.2; Table). PD-L1 expression ≥20% was associated with numerical improvements in mPFS (Table).

Conclusions

G + D had a high discontinuation rate due to liver related TRAEs and there was no additional benefit vs historical data for G alone. However, tumours expressing PD-L1 had favourable PFS and could be investigated further.

Clinical trial identification

NCT02088112; March 14, 2014.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Lauren McNally, MSci, of CMC CONNECT, a division of McCann Health Medical Communications Ltd, Glasgow, UK, with funding from AstraZeneca PLC, in accordance with Good Publication Practice (GPP3) guidelines.

Legal entity responsible for the study

MedImmune LLC (a wholly owned subsidiary of AstraZeneca PLC).

Funding

AstraZeneca PLC.

Disclosure

T. Yeh, W. Tang, M. Tang, H.K. Angell, M.P. Roudier, M. Marotti: Employee: AstraZeneca. R. Taylor: Employee, contractor: AstraZeneca. D.L. Gibbons: Advisory boards/research funding: AstraZeneca. All other authors have declared no conflicts of interest.

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Proffered Paper session III Proffered Paper session

104O - IMpower150: An exploratory analysis of efficacy outcomes in patients with EGFR mutations

Presentation Number
104O
Lecture Time
08:42 - 08:54
Speakers
  • M. Reck (Grosshansdorf, Germany)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Fri, 12.04.2019
Time
08:30 - 10:00
Authors
  • M. Reck (Grosshansdorf, Germany)
  • R. Jotte (Denver, CO, United States of America)
  • T. Mok (Shatin, Hong Kong PRC)
  • D. Lim (Singapore, Singapore)
  • F. Cappuzzo (Ravenna, Italy)
  • F. Orlandi (Santiago, Chile)
  • D. Stroyakovskiy (Moscow, Russian Federation)
  • N. Nogami (Matsuyama, Japan)
  • D. Rodríguez-Abreu (Las Palmas, Spain)
  • D. Moro-Sibilot (Grenoble, France)
  • C. Thomas (Scarborough, ME, United States of America)
  • F. Barlesi (Marseille, CEDEX 20, France)
  • G. Finley (Pittsburgh, PA, United States of America)
  • M. Nishio (Tokyo, Japan)
  • A. Lee (South San Francisco, CA, United States of America)
  • G. Shankar (South San Francisco, CA, United States of America)
  • W. Yu (South San Francisco, CA, United States of America)
  • M. Socinski (Orlando, FL, United States of America)

Abstract

Background

Atezolizumab (atezo; anti–PD-L1) inhibits PD-L1 to restore anticancer immunity; bevacizumab (bev) may enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumour infiltration. Atezo + bev + chemotherapy (chemo) prolonged PFS and OS vs bev + CP in pts with first-line nonsquamous NSCLC in the randomised Ph III IMpower150 study, including pts with EGFR or ALK genomic alterations. The purpose of this analysis is to focus on the efficacy of atezo and/or bev with chemo in pts with EGFR mutations (EGFR-mt).

Methods

The 1202 enrolled pts received atezo (A) 1200 mg + bev (B) 15 mg/kg + carboplatin (C) AUC 6 + paclitaxel (P) 200 mg/m2 (ABCP) or A + C + P (ACP) or B + C + P (BCP) by IV q3w for 4 or 6 cycles per investigator (INV) decision, then q3w maintenance with atezo + bev, atezo or bev, respectively. Primary endpoints were OS and INV-assessed PFS in the ITT–wild-type population (pts with no EGFR or ALK genomic alterations). Exploratory analyses included OS and INV-assessed PFS in pts with EGFR-mt disease, pts with sensitising EGFR-mt and pts with EGFR-mt disease with prior TKI therapy.

Results

These data represent ≥ 20-mo follow-up (data cutoff: 22 Jan 2018) in the ITT population. 124 pts were EGFR-mt; 91 with a sensitising mutation. Baseline characteristics of EGFR-mt pts across treatment arms were generally comparable to the ITT population. OS was improved with ABCP vs BCP in EGFR-mt pts, especially in pts with sensitising EGFR-mts (HR, 0.31 [95% CI: 0.11, 0.83]). This benefit extended to PFS (HR, 0.41 [95% CI: 0.23, 0.75]). See table for full efficacy results. Safety was similar between the EGFR-mt and ITT populations.

Conclusions

IMpower150 is the first randomised Ph III trial of a checkpoint inhibitor to show a benefit in pretreated EGFR-mt pts. Adding atezo to standard-of-care bev and chemo provided survival benefit in EGFR-mt pts who have failed TKIs, for whom this regimen may represent a new treatment option.

Clinical trial identification

NCT02366143.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Jessica Men, PharmD, 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

M. Reck: Speakers bureau, consulting, advisory role: Roche, Lilly, Pfizer, BI, AZ, MSD, BMS, Merck, Novartis, Celgene; Other (support of parent study, funding of editorial support): Roche. R. Jotte: Speakers bureau; travel, accommodations, expenses: Bristol-Myers Squibb; Other (support of parent study, funding of editorial support): Roche. T.S.K. Mok: Honoraria, consult/ad role, research: AZ, BI, BMS, Merck, NVS, Pfizer, Roche/GNE; Honoraria, consult/ad role: LLY; Consult/Ad Role: ACEA, Celgene, geneD, Ignyta, OGXI, Vertex; Consult/ad role, research: Clovis, SFJ; Research: Eisai, Taiho; Stock: Sanomics, Hutch. D.W-T. Lim: Honoraria: AZ, BI, Novartis, MSD, Pfizer, Roche, Takeda, Taiho; Research grants (institution): BMS; Stock: Clearbridge Biomedics Pte Ltd, Mesh Bio Pte Ltd; Other (support of parent study, funding of editorial support): Roche. F. Cappuzzo: Speakers/Advisory board: Roche, AZ, BMS, Pfizer, MSD, Takeda; Other (support of parent study, funding of editorial support): Roche. F. Orlandi: Consult/ad role: AZ, Lilly; Consult/ad role, travel, research: Roche, BMS, MSD; Consult/ad role, travel: Pfizer; Speaker, travel, research: MedImm; Research: Amgen, BI, Astellas, Celltrion. D. Stroyakovskiy, C.A. Thomas: Support of parent study, funding of editorial support: Roche. N. Nogami: Honoraria: AZ, Pfizer, Ono Pharmaceutical, Kyowa Hakko Kririn, Taiho, Chugai, Eli Lilly, BI, MSD; Other (support of parent study and funding of editorial support): Roche. D. Rodríguez-Abreu: Speakers bureau: MSD, Roche, BMS, AZ, Pfizer; Other (support of parent study and funding of editorial support): Roche. D. Moro-Sibilot: Honoraria; Consulting/advisory role, travel, accommodations, expenses: Roche, MSD, Pfizer, BMS, AZ; Honoraria, consulting/advisory role: Novartis, Lilly; Other (support of parent study, funding of editorial support): Roche. F. Barlesi: Support of parent study, funding of editorial support: Roche; Personal fees: AZ, BMS, BI, Clovis, Lilly, Roche, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda; Consulting/advisory: MSD, Takeda. G. Finley: Speakers: BMS, BI, Astellas Medivation, Merck; Support of parent study, funding of editorial support: Roche. M. Nishio: Speakers/Ad board, research grant: Ono Pharma, BMS, Pfizer, Chugai, Lilly, Taiho, AZ, MSD, Novartis; Speakers/Ad board: BI, Sankyo, Merck; Research Grant: Astellas; Support of parent study, funding of editorial support: Roche. A. Lee: Employee/Stock: Genentech; Support of parent study, funding of editorial support: Roche. G. Shankar, W. Yu: Employee: Genentech; Support of parent study, funding of editorial support: Roche. M.A. Socinski: Honoraria/speakers bureau/research funding: Genentech; Support of parent study, funding of editorial support: Roche.

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Proffered Paper session III Proffered Paper session

107O - Crizotinib in advanced ROS1-rearranged non-small cell lung cancer (NSCLC): Overall survival (OS) and updated safety from PROFILE 1001

Presentation Number
107O
Lecture Time
09:33 - 09:45
Speakers
  • A. Shaw (Boston, MA, United States of America)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Fri, 12.04.2019
Time
08:30 - 10:00
Authors
  • A. Shaw (Boston, MA, United States of America)
  • G. Riely (New York, NY, United States of America)
  • Y. Bang (Seoul, Korea, Republic of)
  • D. Kim (Seoul, Korea, Republic of)
  • D. Camidge (Aurora, CO, United States of America)
  • G. Shapiro (Boston, MA, United States of America)
  • T. Usari (Milano, Italy)
  • S. Wang (La Jolla, CA, United States of America)
  • K. Wilner (San Diego, United States of America)
  • J. Clark (Boston, MA, United States of America)
  • S. Ou (Orange, CA, United States of America)

Abstract

Background

In the ongoing phase 1 PROFILE 1001 study (NCT00585195), crizotinib provided a meaningful clinical benefit for patients (pts) with advanced ROS1-rearranged NSCLC, as evidenced by a high objective response rate (72%) and rapid, substantial and durable responses (median duration of response, 18 months [mo]); in addition, crizotinib was well-tolerated (Shaw, N Engl J Med, 2014). Here, we present OS results and updated safety (additional follow-up >3 years) in these pts.

Methods

Pts with histologically confirmed NSCLC containing ROS1 rearrangements were enrolled and treated with oral crizotinib 250 mg twice daily (BID). ROS1 status was assessed by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction.

Results

Between October 2010 and June 2018, 53 pts with ROS1-rearranged NSCLC were treated with crizotinib; median duration of treatment was 22 mo (95% confidence interval [CI]: 15, 36). At the time of data cutoff (June 30, 2018), 12 pts (22.6%) remained on treatment. A total of 26 deaths (49.1%) occurred over a median follow-up period of 63 mo. Median OS was 51 mo (95% CI: 29, not reached) and the probabilities of survival at 12, 24 and 48 mo were 78.8%, 67.0% and 50.7%, respectively. With a median treatment duration nearly 8 mo longer than that for the primary endpoint analysis and 30.2% of patients on treatment for more than 4 years, no new safety signals were noted. The most common grade 3 treatment-related adverse events (TRAEs; in ≥ 5% of pts) were hypophosphatemia (15.1%) and neutropenia (9.4%); no grade 4 TRAEs or treatment-related deaths were reported. With longer follow-up, there were no permanent discontinuations associated with TRAEs.

Conclusions

The results of the OS analysis and updated safety information from PROFILE 1001 continue to support the favorable benefit/risk profile of crizotinib 250 mg BID for the treatment of patients with advanced ROS1-positive NSCLC.

Clinical trial identification

NCT00585195.

Editorial acknowledgement

Editorial assistance was provided by Vasupradha Vethantham, PhD, of inScience Communications, Springer Healthcare (New York, NY, USA), with funding from Pfizer, Inc.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer, Inc.

Disclosure

A. Shaw: Fees for consulting/advisory board roles: ARIAD/Takeda, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Foundation Medicine Genentech, Ignyta, KSQ Therapeutics, Loxo, Novartis, Pfizer, Roche, Taiho; Honoraria: Novartis, Pfizer, Roche; Research funding to institution: Daiichi Sankyo, Ignyta, Novartis, Pfizer, Roche/Genentech, TP Therapeutics. Y-J. Bang: Advisory boards: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Daiich-Sankyo, Eli Lilly, GreenCross, Genentech/Roche, Hanmi, Novartis,  Merck Serano,  MSD, Samyang Biopharm, Taiho; Research funding to institution: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Boeringer Ingelheim, Boston Biomedical, CKD Pharma, Curis, Daiichi Sankyo, Eli Lilly, FivePrime, Glaxo Smith-Kline, Genentech/Roche, Green Cross, MacroGenics, Merck Serano, MSD, Novartis, Pfizer, Ono, Takeda, Taiho. D.R. Camidge: Advisory boards: AbbVie, ARIAD, Array, Celgene, Clovis, Eli Lilly, G1 Therapeutics (DSMB), Genoptix, Ignyta, Mersana Therapeutics, Novartis, Orion, Roche/Genentech, Takeda; Research for investigator-initiated trials: ARIAD, Takeda. G.J. Riely: Funding to institution: Pfizer for the conduct of this research; Research support to institution: Novartis, Roche, Takeda. Compensated consultant: Genentech/Roche. G.I. Shapiro: Research funding to the Dana-Farber Cancer Institute: Pfizer for the conduct of the study; Advisory boards: Eli Lilly, G1 Therapeutics, Merck/EMD Serono, Roche, Pfizer, Vertex Pharmaceuticals. T. Usari, S.C. Wang, K. Wilner: Employee, holds stock: Pfizer. J.W. Clark: Institutional research funding: Pfizer. S-H.I. Ou: Fees for consulting/Advisory board: Pfizer; Research funding to institution: Eli Lilly, Merck/EMD Serono, Pfizer. All other authors have declared no conflicts of interest.

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Proffered Paper session I Proffered Paper session

69O - Comprehensive profiling of genomic and TCR repertoire in localized stage lung adenocarcinomas from a prospective cohort study

Presentation Number
69O
Lecture Time
16:45 - 17:00
Speakers
  • K. Chen (Beijing, China)
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
Wed, 10.04.2019
Time
16:30 - 18:15
Authors
  • K. Chen (Beijing, China)
  • J. Bai (Beijing, China)
  • H. Zhao (Beijing, China)
  • F. Yang (Beijing, China)
  • C. Zhang (Beijing, China)
  • Y. Wang (Beijing, China)
  • L. Chang (Beijing, China)
  • Y. Guan (Beijing, China)
  • X. Yi (Beijing, China)
  • L. Feng (Beijing, China)
  • K. Zhang (Beijing, China)
  • S. Cheng (Beijing, China)
  • J. Wang (Beijing, China)

Abstract

Background

Recently, neoadjuvant targeted therapy and immunotherapy have presented a promising clinical effect for localized stage non-small cell lung cancer. However, the characteristics and relationship of genomic and immune profiling in surgical lung adenocarcinomas has been poorly delineated to date.

Methods

We prospectively enrolled 100 consecutive patients with pulmonary nodule who intended to undergo curative lung resection during June 2017 to July 2018 (NCT03320044). We investigated the TCR repertoire using next-generation deep sequencing of the complementarity determining region 3 (CDR3) of the TCR β chain in the tissue and WBC samples. Target-capture deep sequencing of 1021 genes was used to detect genomic variations in both tissue and paired plasma samples.

Results

EGFR (65.4%), TP53 (36.5%) and KRAS (11.5%) mutated most frequently. KRAS (84.6%) was enriched in mucinous adenocarcinoma. High invasive subtype and no ground-glass opacity status is more likely to be increasing tissue TMB (p = 0.0016, p = 0.0012), higher T-cell clonality (p = 0.05, p = 0.05), and more HLA-LOH event (p = 0.038, p = 0.035). A median of TNB was 2 neoantigens/Mb and showed positive relation with TMB (r = 0.97, p < 0.0001). EGFR-mutant co-occurring mutations were enriched TGF-beta, PI3K-Akt, hippo and Leukocyte trans-endothelial migration pathway (q < 0.05). Lower TCR clonality was shown in patients with EGFR mutation and co-occurring hippo or Leukocyte trans-endothelial migration pathway. Alterations in DNA damage response (DDR) pathways were observed in 15.8% patients, and these patients showed higher clonality (p = 0.03). 35.3%(24/68) ctDNA-positive were found in Stage I with a mean ctDNA abundance of 0.18% (ranged from 0.012 to 3.3%), which suggested the challenge of bTMB in biomarker study of early-stage LUAD. Analysis of TCR repertoire from available paired WBC showed no obvious characteristics.

Conclusions

This is the first prospective study integrating the correlation of genomic alteration and T-cell receptor in localized surgical LUAD. Analysis of co-altered pathway of EGFR-mutant LUAD and immune microenviroment will provide a better understanding in choosing biomarkers and optimal benefit patients for neoadjuvant therapy.

Clinical trial identification

NCT03320044.

Legal entity responsible for the study

Jun Wang.

Funding

National Natural Science Foundation of China (No.81602001).

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper session II Proffered Paper session

55O - Radiogenomic signatures of NSCLC brain metastases: A potential non-invasive imaging marker for ALK mutation

Presentation Number
55O
Lecture Time
09:51 - 10:03
Speakers
  • S. Wadhwa (Mumbai, India)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Thu, 11.04.2019
Time
09:00 - 10:30
Authors
  • S. Wadhwa (Mumbai, India)
  • G. Krishna.b (Mumbai, India)
  • M. Malhotra (Mumbai, India)
  • K. Prabhash (Mumbai, India)
  • V. Noronha (Mumbai, India)
  • A. Joshi (Mumbai, India)
  • V. Patil (Mumbai, India)
  • A. Mahajan (Mumbai, India)

Abstract

Background

NSCLC harbouring ALK rearrangement has a higher risk of developing brain metastases. Literature on MR Imaging radiogenomics (MRI-R) as predictors of ALK mutation is limited and less investigated. The aim of our study was to evaluate the semantic MRI-R parameters of NSCLC brain metastases and their correlation with ALK status.

Methods

We analyzed clinical data on 75 patients who were tested for ALK mutation and underwent MR imaging at diagnosis. Multiparametric MRI was performed in all cases. The associations between ALK mutation status and clinical features specifically age, sex, smoking, histology, TNM stage and imaging variables of brain metastasis, were analyzed using descriptive analysis (chi-square test) and univariate logistic regression analysis.

Results

There were 46 ALK positive and 29 ALK negative cases that were subjected to MRI-R analysis. ALK positive were predominantly young (83%) and non-smokers (87%) (p < 0.001). Statistically significant difference (p < 0.001) was observed in lesion morphology and its T2W border, fuzzy and infiltrative border with hypointense peripheral solid rim in ALK positive while well defined border and no solid rim in ALK negative. Predominant signal on T1W imaging was hypointense (p < 0.001) in ALK negative, whereas heterogeneity was marker of ALK positive status on T1W (p < 0.001). Lesions in ALK negative group showed central restriction on DW images (p-0.001) and peripheral restriction of the solid rim was characteristic of ALK positive (p < 0.001). ALK positive showed thick ring enhancement while patchy enhancement favoured ALK negative. Incidence of meningeal involvement was significantly higher in ALK positive and was absent in 80% of ALK negative (p-0.02). On univariate logistic regression analysis, statistically significant association was found between age, smoking history, T2W lesion morphology, T2W border, restricted diffusion, enhancement and meningeal positivity (p < 0.05).

Conclusions

ALK positive brain metastases have peculiar MR imaging features that can be non-invasive diagnostic and predictive imaging biomarkers. MR radiogenomics have potential role in individualised management of ALK positive NSCLC brain metastasis.

Legal entity responsible for the study

IEC TMH.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper session I Proffered Paper session

83O - Impact of subsequent post-discontinuation immunotherapy on overall survival in patients with unresectable, stage III NSCLC from PACIFIC

Presentation Number
83O
Lecture Time
17:15 - 17:30
Speakers
  • P. Dennis (Gaithersburg, MD, United States of America)
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
Wed, 10.04.2019
Time
16:30 - 18:15
Authors
  • M. Ouwens (London, United Kingdom)
  • A. Darilay (Gaithersburg, MD, United States of America)
  • Y. Zhang (Gaithersburg, MD, United States of America)
  • P. Mukhopadhyay (Gaithersburg, United States of America)
  • H. Mann (Cambridge, United Kingdom)
  • J. Ryan (Cambridge, United Kingdom)
  • P. Dennis (Gaithersburg, MD, United States of America)

Abstract

Background

In cancer trials, pts often receive subsequent lines of anticancer Tx following progression, which, in standard ITT analyses, can lead to bias and underestimation of OS Tx effect. In the phase 3 PACIFIC trial of durvalumab vs. placebo in Stage III NSCLC pts without progression after CRT, both primary endpoints PFS and OS were met, significantly improved with durvalumab. However, after discontinuation, many pts received further anticancer Tx (41% and 54% in the durvalumab and placebo groups), including immunotherapies (IMTs), which may have influenced OS. Using the Rank Preserving Structural Failure Time (RPSFT) model, we quantified the specific impact of subsequent IMT on OS in PACIFIC.

Methods

RPSFT modeling is commonly used for analysis of trials with crossover. By assuming a similar effect for Tx in different sequences, RPSFT is capable to pinpoint the most likely effect size based on observed data. Here, we adapted RPSFT to isolate the likely effect of subsequent IMT by assuming similar mortality risk reduction for nivolumab, pembrolizumab, and durvalumab. RPSFT analyses were applied to quantify health outcomes for two hypothetical scenarios: (1) no subsequent IMT was received by pts in either arm, and (2) among placebo pts who received subsequent Tx (54%), all received IMT as first subsequent Tx, and durvalumab pts received no subsequent IMT, to test if delaying IMT was detrimental.

Results

Among pts randomized to durvalumab and placebo, 8% (38/476) and 22% (53/237), respectively, received subsequent IMT. Within the ITT population, the HR for OS with durvalumab vs. placebo was 0.68 (95% CI, 0.53–0.87), with respective median OS not reached (NR) and 28.7 months. For scenario 1, there was minimal change in OS, with an estimated HR of 0.67 (95% CI, 0.52–0.86) and identical median OS estimates. For scenario 2, the estimated HR was 0.79 (95% CI: 0.62–1.00), with median OS NR and 32.2 months, respectively.

Conclusions

After removing the effects of subsequent IMT, the OS benefit with durvalumab was still evident compared with the ITT analysis. In addition, early Tx with durvalumab after CRT appeared to be associated with improved OS compared with starting IMT after progression.

Clinical trial identification

NCT02125461.

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, PhD, of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M. Ouwens, Y. Zhang, P. Mukhopadhyay: Employment, stock options: AstraZeneca, outside the conduct of the study. A. Darilay, J. Ryan: Employment, stock: AstraZeneca, outside the conduct of the study. H. Mann: Employment: AstraZeneca, outside conduct of the study. P.A. Dennis: Employment, stocks: AstraZeneca, outside the submitted work.

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Proffered Paper session II Proffered Paper session

110O - Plasma circulating tumor DNA analysis (ctDNA) for molecular alteration detection in advanced non-small cell lung cancer (NSCLC) patients (pts) with isolated central nervous system (CNS) metastases (mts)

Presentation Number
110O
Lecture Time
10:03 - 10:15
Speakers
  • M. Aldea (Villejuif, France)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Thu, 11.04.2019
Time
09:00 - 10:30
Authors
  • M. Aldea (Villejuif, France)
  • L. Hendriks (Maastricht, Netherlands)
  • L. Mezquita (Villejuif, France)
  • J. Remon-Masip (Barcelona, Spain)
  • D. Planchard (Villejuif, France)
  • C. Jovelet (Villejuif, France)
  • J. Benitez (Barcelona, Spain)
  • A. Gazzah (Villejuif, France)
  • C. Naltet (Villejuif, France)
  • P. Lavaud (Villejuif, France)
  • L. Lacroix (Villejuif, France)
  • K. Howarth (Cambridge, United Kingdom)
  • C. Morris (Cambridge, United Kingdom)
  • E. Green (Cambridge, United Kingdom)
  • C. Nicotra (Villejuif, France)
  • B. Besse (Villejuif, CEDEX, France)

Abstract

Background

In advanced NSCLC, ctDNA is an emerging tool in molecular profile testing at diagnosis and at resistance to targeted therapies. However, for CNS limited mts, ctDNA might have a reduced accuracy because of low concentrations. Aim: to assess feasibility of ctDNA in NSCLC with isolated CNS disease/progression (PD) (iCNS).

Methods

This is a retrospective analysis of consecutive advanced NSCLC pts treated at Gustave Roussy from 01.2016 to 06.2018 included in 2 prospective studies (CEC-CTC, MSN). Included: any molecular tissue alteration at baseline (EGFR, ALK, BRAF, KRAS, HER2, ROS1, MET, TP53), CNS disease and ≥1 ctDNA sample at diagnosis/PD. CtDNA was performed by next generation sequencing (NGS- InVisionSeq™-Lung). Clinical/molecular/imaging data were collected. CtDNA in iCNS group were compared to systemic PD group (with CNS PD or stable disease, S-CNS). ctDNA was defined as positive if ≥ 1 mutation in the NGS panel.

Results

422/959 screened pts had ≥1 ctDNA sample. 183/422 pts had CNS disease. 58/182 pts had ctDNA sample at time of CNS disease and 66 samples were eligible for inclusion: 21 iCNS and 45 S-CNS (≥1 sample/patient as ≥ 1 PD). In iCNS and S-CNS, pts characteristics were: median age 55 vs 59 years, female gender 94% vs 59%, adenocarcinoma histology 100% vs 93%, smoking history 35% vs 44%, median mts sites at diagnosis 1 vs 2. Prevalence of EGFR mutation at diagnosis was 76 and 61%, ALK rearrangement 18 and 10%, KRAS 6 and 5% in iCNS and in S-CNS, respectively. HER2, TP53, BRAF and MET alterations were present only in S-CNS group (12%, 10%, 5% and 2%). CtDNA was positive in 38% in iCNS vs. 98% in S-CNS groups (Fisher test, p < 0.0001) (Table).

Conclusions

In NSCLC pts with isolated CNS involvement, genomic alterations assessed by ctDNA in plasma had a low detection rate. (Table).

Legal entity responsible for the study

Gustave Roussy Institute, Villejuif, France.

Funding

Has not received any funding.

Disclosure

L. Mezquita: Consulting, advisory role: Roche Diagnostics; Lectures, educational activities: Bristol-Myers Squibb, Tecnofarma, Roche, AstraZeneca; Travel, accommodations, expenses: Chugai. D. Planchard: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. C. Morris, E. Green: Employee, shareholder: Inivata. B. Besse: Sponsored research at Gustave Roussy Cancer Center: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma; Investigator or co-investigator of trials: Nerviano, GSK, Pfizer, Roche-Genentech, Lilly, OSE Pharma, MSD, Celgene, Stemcentrx, Ignyta, AbbVie, Loxo Oncology, AstraZeneca, Blueprint Medicines. All other authors have declared no conflicts of interest.

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Proffered Paper session II Proffered Paper session

21O - EPAC-Lung: Pooled analysis of circulating tumor cells in advanced non-small cell lung cancer

Presentation Number
21O
Lecture Time
09:00 - 09:12
Speakers
  • C. Lindsay (Manchester, United Kingdom)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Thu, 11.04.2019
Time
09:00 - 10:30
Authors
  • C. Lindsay (Manchester, United Kingdom)
  • F. Blackhall (Manchester, United Kingdom)
  • A. Carmel (Villejuif, France)
  • P. Gazzaniga (Rome, Italy)
  • H. Groen (Groningen, Netherlands)
  • M. Krebs (Manchester, United Kingdom)
  • L. Muinelo-Romay (Santiago de Compostela, Spain)
  • K. Pantel (Hamburg, Germany)
  • E. Rossi (Padova, Italy)
  • L. Terstappen (Enschede, Netherlands)
  • H. Wikman (Hamburg, Germany)
  • J. Soria (Gaithersburg, CEDEX, United States of America)
  • F. Farace (Villejuif, France)
  • A. Renehan (Manchester, United Kingdom)
  • C. Dive (Manchester, United Kingdom)
  • B. Besse (Villejuif, CEDEX, France)
  • S. Michiels (Villejuif, France)

Abstract

Background

We assessed the clinical validity of circulating tumor cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a European pooled analysis of individual patient data. This is the largest study of its kind and the first to examine between-centre heterogeneity of CTC identification in NSCLC.

Methods

Nine European NSCLC CTC centers were asked to provide reported/unreported anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 - March 2017. We used Cox regression models, stratified by centre, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinico-pathological models using likelihood ratio (LR) statistics and c-indices.

Results

Seven out of nine eligible centers provided data for 550 eligible patients, including 209 patients whose prognostic information was previously unpublished. CTC counts of ≥ 2 and ≥5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: HR 1.72, p < 0·001; ≥5 CTCs: HR 2.21, p < 0·001) and overall survival (≥2 CTCs: HR 2·18, p < 0·001; ≥5 CTCs: HR 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinico-pathological models (log-transformed CTCs p < 0·0001; ≥2 CTCs p < 0·0001; ≥5 CTCs p < 0·0001), while more moderate improvements were observed with the use of c-index models. There was minor evidence of between-center heterogeneity in the effect on PFS, but not OS.No difference in CTC profile was observed between key NSCLC molecular subsets such as EGFR, ALK, and KRAS.

Conclusions

These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC. CTC count improves prognostication when added to full clinico-pathological predictive models. ≥2 CTCs is an appropriate cutoff to move towards establishing clinical utility.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C.R. Lindsay: Institutional funding for an ongoing phase II trial for which I am PI; Supported by Roche as part of an ESMO translational fellowship awarded in 2014-2016. F.H. Blackhall: Grants: AstraZeneca, Novartis, Pfizer, Amgen, BMS; Consultancy fees: Cell Medica, MSD; Speaker bureau: BI; Advisory board work: Regeneron, Medivation, AbbVie, Takeda, Roche, Ibsen. M.G. Krebs: Advisory board: J&J. L. Terstappen: Inventor on a number of US patents related to CellSearch, rights of which assigned to Johnson&Johnson, CellSearch kits obtained from Johnson&Johnson through a collaborative agreement with the MCBP. J-C. Soria: Consultancy fees: AZ, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, Takeda; Full time employee: MedImmune; Shareholder: AZ, Gritstone. All other authors have declared no conflicts of interest.

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Proffered Paper session II Proffered Paper session

108O - Treatment duration of brigatinib in patients enrolled in the international expanded access program (EAP)

Presentation Number
108O
Lecture Time
09:12 - 09:24
Speakers
  • X. Pan (Cambridge, MA, United States of America)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Thu, 11.04.2019
Time
09:00 - 10:30
Authors
  • M. Lin (Cambridge, United States of America)
  • X. Pan (Cambridge, MA, United States of America)
  • P. Hou (Cambridge, MA, United States of America)
  • S. Allen (Cambridge, MA, United States of America)
  • P. Baumann (Cambridge, MA, United States of America)
  • M. Hochmair (Vienna, Austria)

Abstract

Background

Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor for the treatment of advanced ALK+ non-small cell lung cancer (NSCLC). In June 2016, the international EAP was opened to enable access to brigatinib prior to commercial launch for patients with unmet medical need, including those who had exhausted available therapies or were unable to participate in a clinical study. This retrospective analysis evaluated real-world treatment duration using brigatinib EAP shipment and discontinuation data.

Methods

This analysis included data from patients with locally advanced or metastatic ALK+ NSCLC who were resistant or intolerant to at least one ALK inhibitor and had received brigatinib across multiple lines of therapy through the EAP between July 2016 and Nov 7, 2018; most patients were European. Treatment duration was recorded for patients with confirmed discontinuation, as stated on their discontinuation forms. Discontinuation was assumed for patients without confirmed discontinuation if there was a gap of > 120 days between data cutoff and last medication shipment date. Time to treatment discontinuation was estimated from Kaplan-Meier curves. Subgroup analyses were conducted based on whether patients had received prior alectinib, ceritinib, or lorlatinib.

Results

A total of 604 patients (42.4% male; median age, 58.0 years) received brigatinib, with the majority receiving brigatinib as a 3+ line agent. Across all lines of therapy, median time to brigatinib discontinuation was 10.95 months (95% CI 8.65 − 13.88). Median time to discontinuation (95% CI) was 8.72 months (7.50 − 14.93) after alectinib (N = 111), 10.33 months (8.13 − 13.62) after ceritinib (N = 249) and 7.5 months (4.47−NE) after lorlatinib (N = 37). Few patients reported discontinuation due to adverse events (N = 4, 0.7%).

Conclusions

In the real world, despite a heterogeneous patient population treated with multiple prior ALK inhibitors, time to discontinuation of brigatinib (from all lines) was almost one year. Although complete disease progression status of the patients was absent, this time-to-discontinuation analysis indicates encouraging benefit with a manageable safety profile for brigatinib.

Editorial acknowledgement

Jane Kondejewski, PhD, SNELL Medical Communicaiton, Inc.

Legal entity responsible for the study

Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Funding

Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Disclosure

M.M. Lin, X. Pan, P. Hou, S. Allen, P. Baumann: Employee: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited which funded this study. M.J. Hochmair: Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche; Consulting, advisory roles: Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche.

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