Hall A2 - Room 18 Proffered Paper session
Date
20.10.2018
Time
16:30 - 18:20
Location
Hall A2 - Room 18
Chairs
  • Andrés Cervantes (Valencia, ES)
  • Josep Tabernero (Barcelona, ES)
Presidential Symposium 1 Proffered Paper session

LBA1_PR - IMpassion130: Results from a global, randomised, double-blind, phase 3 study of atezolizumab (atezo) + nab-paclitaxel (nab-P) vs placebo + nab-P in treatment-naive, locally advanced or metastatic triple-negative breast cancer (mTNBC)

Presentation Number
LBA1_PR
Lecture Time
16:30 - 16:45
Speakers
  • Peter Schmid (London, GB)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
20.10.2018
Time
16:30 - 18:20

Abstract

Background

mTNBC is the breast cancer subtype with worst prognosis and is typically treated with chemo. Atezo (anti–PD-L1) combined with nab-P (A+nab-P) demonstrated safety and clinical activity in mTNBC (Pohlmann AACR 2018). Here we report final PFS and initial interim OS results from IMpassion130, a ph 3, double-blind, randomised study evaluating 1L A+nab-P in mTNBC

Methods

Eligible patients (pts) with histologically documented mTNBC, ECOG PS 0-1 and tumour tissue for PD-L1 testing were randomised 1:1 to IV atezo 840 mg or placebo (P) on d1 and 15 (q2w) + nab-P 100 mg/m2 on d1, 8 and 15 of a 28-d cycle until progression. Stratification factors were prior taxanes, liver mets and tumour PD-L1 status on immune cells (positive: ≥1%). Co-primary endpoints (EPs) were PFS (ITT and PD-L1+ pts) and OS (ITT and, if significant, PD-L1+ pts). Key secondary EPs were ORR and DOR.

Results

At data cutoff 17 Apr 2018, median follow-up was 12.9 mo. In the A+nab-P and P+nab-P arms, respectively (n = 451 each), median age was 55 and 56 y; 57% and 60% had ECOG PS 0 and 63% each had prior (neo)adjuvant treatment. Efficacy data are in the Table. All-cause AEs occurred in 99% (G3-4, 49%) and 98% (G3-4, 42%) of evaluable pts in the A+nab-P and P+nab-P arms (n = 452, 438), respectively. Nausea, cough, neutropenia, pyrexia and hypothyroidism were ≥5% higher with A+nab-P. 3/6 G5 AEs in A+nab-P and 1/3 in P+nab-P pts were related to either atezo, P or nab-P. G3-4 AEs of special interest occurred in 8% of A+nab-P and 4% of P+nab-P pts.

Conclusions

IMpassion130 met its co-primary PFS EP in ITT and PD-L1+ pts, with clinically meaningful OS benefit seen at interim OS analysis in PD-L1+ pts. A+nab-P was well tolerated, with a safety profile consistent with each agent. This first positive ph 3 mTNBC immunotherapy study highlights A+nab-P as a new therapy for untreated PD-L1+ pts.

Table. IMpassion130a efficacy results

ITT population

PD-L1+ subpopulationb

A+nab-P
(n = 451)

P+nab-P
(n = 451)

A+nab-P
(n = 185)

P+nab-P
(n = 184)

Co-primary endpointsc

Median PFS (95% CI), mo

7.2 (5.6, 7.5)

5.5 (5.3, 5.6)

7.5 (6.7, 9.2)

5.0 (3.8, 5.6)

PFS HR (95% CI; P value)

0.80 (0.69, 0.92; P = 0.0025)

0.62 (0.49, 0.78); P < 0.0001

Median OS (95% CI), mo

21.3 (17.3, 23.4)

17.6 (15.9, 20.0)

25.0 (22.6, NE)

15.5 (13.1, 19.4)

OS HR (95% CI; P value)

0.84 (0.69, 1.02; P = 0.0840)

0.62 (0.45, 0.86); P = 0.0035d

Secondary endpointsc

ORR-evaluable pts, n

450

449

185

183

ORR (95% CI), %

56 (51, 61)

46 (41, 51)

59 (51, 66)

43 (35, 50)

Difference in ORR (95% CI), %; P value (Cochran-Mantel-Haenszel)

10 (3, 17); P = 0.0021

16 (6, 27); P = 0.0016

DOR-evaluable pts, n

252

206

109

78

Median DOR (95% CI), mo

7.4 (6.9, 9.0)

5.6 (5.5, 6.9)

8.5 (7.3, 9.7)

5.5 (3.7, 7.1)

OS results based on initial interim OS analysis.

DOR, duration of response; HR, hazard ratio; ITT, intent-to-treat; NE, not estimable; ORR, objective response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival.

a NCT02425891.

b PD-L1 positivity was defined per the VENTANA SP142 IHC assay as PD-L1 expression on tumour-infiltrating immune cells ≥ 1%.

c PFS, ORR and DOR evaluated per investigator-assessed Response Evaluation Criteria in Solid Tumors v1.1.

d Not formally tested due to hierarchical study design.

Clinical trial identification

NCT02425891

Editorial Acknowledgement

Medical writing support provided by Ashley J. Pratt, PhD, CMPP, of Health Interactions.

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Presidential Symposium 1 Proffered Paper session

Invited discussant

Lecture Time
16:45 - 17:00
Speakers
  • Giuseppe Curigliano (Milan, IT)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
20.10.2018
Time
16:30 - 18:20
Presidential Symposium 1 Proffered Paper session

LBA2_PR - Overall survival (OS) with palbociclib plus fulvestrant in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2_) advanced breast cancer (ABC): Analyses from PALOMA-3

Presentation Number
LBA2_PR
Lecture Time
17:00 - 17:15
Speakers
  • Massimo Cristofanilli (Chicago, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
20.10.2018
Time
16:30 - 18:20

Abstract

Background

Endocrine therapy (ET)–resistant ABC is dependent on cyclin dependent kinase (CDK) 4/6. In the prospective, randomized, double-blind, phase 3 PALOMA-3 study, the CDK4/6 inhibitor PAL in combination with FUL significantly improved progression-free survival (PFS) vs placebo (PBO)+FUL (median PFS, 11.2 vs 4.6 mo; absolute difference, 6.6 mo; hazard ratio [HR] 0.50 [95% CI, 0.40–0.62]; P<0.000001). Here, we report OS analysis with a median follow up of 44.8 mo.

Methods

HR+/HER2– ABC (N=521) patients (pts) who had relapsed or progressed on prior ET were randomized 2:1 to PAL (125 mg/d orally, schedule 3/1) + FUL (500 mg per standard of care) or PBO+FUL. Primary endpoint was investigator-assessed PFS. A key secondary endpoint was OS. OS analysis occurred when approximately 60% (n≈310) of the 521 pts died.

Results

Median OS improved with PAL+FUL vs PBO+FUL by an absolute difference of 6.9 mo (Table). In pts with sensitivity to prior ET, the absolute improvement in median OS was 10.0 mo with PAL+FUL vs PBO+FUL. In pts without visceral disease, median OS significantly improved with PAL+FUL vs PBO+FUL (11.5 mo). Time to end of the next-line treatment was 18.8 (PAL+FUL) and 14.1 (PBO+FUL) mo (HR 0.68 [95% CI, 0.56–0.84]; P<0.0001). Improvements in median OS, although not statistically significant at the prespecified level, were shown with PAL+FUL vs PBO+FUL regardless of ESR1 mutation status or prior lines of therapy. Median time on subsequent therapy was similar in both arms; median time to chemotherapy was 17.5 (PAL+FUL) and 8.8 (PBO+FUL) mo (HR 0.58; P<0.000001). No new safety signals were observed with longer follow-up.

Table. OS in the ITT Population and by Subgroup
Subgroup n (%) HR (95% CI) PAL+FUL
median OS (95% CI)
PBO+FUL
median OS (95% CI)
1-sided
P value
Interaction
P value
ITT, stratified 521 (100) 0.81 (0.64–1.03) 34.9 (28.8–40.0) 28.0 (23.6–34.6) 0.043
ITT, unstratified 521 (100) 0.79 (0.63–1.00) 34.9 (28.8–40.0) 28.0 (23.6–34.6) 0.025
Sensitivity to previous endocrine therapy
Endocrine sensitive 410 (78.7) 0.72 (0.55–0.94) 39.7 (34.8–45.7) 29.7 (23.8­–37.9) 0.124
Endocrine resistant 111 (21.3) 1.14 (0.71–1.84) 20.2 (17.2–26.4) 26.2 (17.5–31.8)
Site of metastatic disease
Visceral disease 311 (59.7) 0.85 (0.64–1.13) 27.6 (24.4–31.2) 24.7 (20.8–31.8) 0.442
Nonvisceral disease 210 (40.3) 0.69 (0.46–1.04) 46.9 (39.3–NE) 35.4 (24.6–NE)
Menopausal status at study entry
Postmenopausal 413 (79.3) 0.73 (0.57–0.95) 34.8 (28.8–40.1) 27.1 (22.8–32.1) 0.251
Pre/perimenopausal 108 (20.7) 1.07 (0.61–1.86) 38.0 (24.4–NE) 38.0 (22.2–NE)
FUL=fulvestrant; HR=hazard ratio; ITT=intent-to-treat; NE=not estimable; OS=overall survival; PAL=palbociclib; PBO=placebo.

Conclusions

In HR+/HER2– ABC pts, PAL+FUL showed a clinically meaningful improvement in OS (6.9 mo vs PBO+FUL), especially in pts with sensitivity to prior ET. The absolute difference of PFS gain was maintained in OS.

Funding: Pfizer (NCT01942135)

Clinical trial identification

(NCT01942135)

Editorial Acknowledgement

Editorial support was provided by Jennifer Fetting, PhD, and Kevin O’Regan, PhD, of Complete Healthcare Communications, LLC (North Wales, PA), a CHC Group company, and funded by Pfizer Inc.

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Presidential Symposium 1 Proffered Paper session

Invited Discussant

Lecture Time
17:15 - 17:30
Speakers
  • Fatima Cardoso (Lisbon, PT)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
20.10.2018
Time
16:30 - 18:20
Presidential Symposium 1 Proffered Paper session

LBA3_PR - Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): results of the Phase 3 SOLAR-1 trial

Presentation Number
LBA3_PR
Lecture Time
17:30 - 17:45
Speakers
  • Fabrice André (Villejuif, FR)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
20.10.2018
Time
16:30 - 18:20

Abstract

Background

Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway can occur due to PIK3CA mutations, present in ~40% of patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) ABC. The Phase 3 randomized, double-blind SOLAR‑1 trial (NCT02437318) investigated the efficacy and safety of ALP (α-specific PI3K inhibitor) + FUL in pts with HR+, HER2– ABC.

Methods

Men/postmenopausal women with HR+, HER2– ABC and 1 prior line of endocrine therapy were randomized (1:1) to ALP (300 mg/day) + FUL (500 mg every 28 days + Cycle 1 Day 15) or placebo (PBO) + FUL. Primary endpoint was locally assessed progression-free survival (PFS) in the PIK3CA-mutant (mut) cohort; PFS was analyzed in the non-mut cohort as a proof of concept (PoC). Safety was assessed in the total population. Other analyses were tumor response and PFS by important prognostic subgroups, including PIK3CA mutation exon/domain and subtype.

Results

572 pts enrolled; 341 had PIK3CA-mut ABC by tissue. Primary endpoint was met; PFS in the mut cohort was significantly longer with ALP+FUL vs PBO+FUL (HR 0.65; 95% CI 0.50–0.85; P=0.00065; median 11.0 vs 5.7 months [mo]); median follow-up was 20.0 mo. Secondary endpoint of locally assessed PFS in the non-mut cohort did not meet predefined PoC criteria (HR 0.85; 95% CI 0.58–1.25; median 7.4 vs 5.6 mo). In pts with measurable, PIK3CA-mut ABC (n=262), overall response rate was 36% for ALP+FUL vs 16% for PBO+FUL (p=0.0002). Overall, most frequent all-grade (G) adverse events (AEs; single preferred term; ALP+FUL vs PBO+FUL) were hyperglycemia (64% vs 10%), diarrhea (58% vs 16%), nausea (45% vs 22%), decreased appetite (36% vs 10%) and rash (36% vs 6%). G 3/4 hyperglycemia (fasting plasma glucose >250 mg/dL) was observed in 37% of patients for ALP+FUL vs <1% for PBO+FUL; G 3/4 rash in 10% vs <1%. Discontinuations of ALP+FUL/PBO+FUL due to AEs were 5% vs 1%.

Conclusions

ALP+FUL met the primary endpoint by significantly extending PFS vs PBO+FUL and demonstrated a manageable tolerability profile. This is the first study to show statistically significant, clinically meaningful PFS treatment improvement with an α-specific PI3K inhibitor in PIK3CA-mut HR+, HER2– ABC.

Clinical trial identification

NCT02437318

May 7, 2015

Editorial Acknowledgement

Editorial assistance was provided by John Munro of ArticulateScience Ltd.

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Presidential Symposium 1 Proffered Paper session

283O_PR - Phase III trial of chidamide, a subtype-selective histone deacetylase (HDAC) inhibitor, in combination with exemestane in patients with hormone receptor-positive advanced breast cancer

Presentation Number
283O_PR
Lecture Time
17:45 - 18:00
Speakers
  • Zefei Jiang (Beijing, CN)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
20.10.2018
Time
16:30 - 18:20

Abstract

Background

Chidamide (CS055/Tucidinostat/Epidaza®) is an oral subtype-selective HDAC inhibitor. An exploratory clinical study has demonstrated the encouraging antitumor activity of chidamide in combination with exemestane in hormone receptor (HR)-positive advanced breast cancer (ABC) patients.

Methods

This randomized, double-blind, placebo controlled study involved postmenopausal patients with HR-positive, HER2-negative ABC failed to tamoxifen and/or nonsteroidal aromatase inhibitor. Eligible patients were randomly assigned (2:1) to two arms (chidamide 30 mg twice a week plus exemestane 25 mg daily or placebo plus exemestane). The primary endpoint was progression-free survival (PFS), assessed by investigator. Secondary endpoints were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety.

Results

365 patients were enrolled at 22 centers in China, with 244 in the chidamide group and 121 in the placebo group. The median PFS was 7.4 months (95% confidence interval [CI], 5.5 to 9.2) with chidamide–exemestane and 3.8 months (95% CI, 3.7 to 5.5) with placebo–exemestane (hazard ratio for disease progression or death, 0.755; 95% CI, 0.582 to 0.978; P=0.0336). ORR was 18.4% and 9.1%(P=0.026), and CBR was 46.7% and 35.5%(P=0.034)in the chidamide group and placebo group, respectively. Overall survival results were not mature at the time of the analysis. The most common grade 3 or 4 adverse events (AE) in the chidamide group were neutropenia (50.8% vs. 2.5% in the placebo group), thrombocytopenia (27.5% vs. 2.5%), and leucopenia (18.8% vs. 2.5%). Serious adverse events occurred in 51 (20.9%) patients in the chidamide group and 7 (5.8%) patients in the placebo group. No treatment related death was reported.

Conclusions

This is the first oral HDAC inhibitor combined with exemestane in a pivotal clinical study to demonstrate PFS benefit and manageable adverse effect in HR–positive ABC patients progressed after prior endocrine therapy.

Clinical trial identification

NCT02482753

Editorial Acknowledgement

The authors thank B. Wang, T. Liu, and J. Gao for their contributions to the study

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Presidential Symposium 1 Proffered Paper session

Invited discussant

Lecture Time
18:00 - 18:20
Speakers
  • Rebecca Dent (Singapore, SG)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
20.10.2018
Time
16:30 - 18:20