IMpassion130: Results from a global, randomised, double-blind, phase 3 study of atezolizumab (atezo) + nab-paclitaxel (nab-P) vs placebo + nab-P in...

Date 20 October 2018
Event ESMO 2018 Congress
Session Presidential Symposium 1
Topics Anticancer Agents
Immunotherapy
Breast Cancer
Presenter Peter Schmid
Authors P. Schmid1, S. Adams2, H.S. Rugo3, A. Schneeweiss4, C.H. Barrios5, H. Iwata6, V. Dieras7, R. Hegg8, S. Im9, G.S. Wright10, V. Henschel11, L. Molinero12, S.Y. Chui13, R. Funke14, A. Husain15, E.P. Winer16, S. Loi17, L.A. Emens18
  • 1Centre Of Experimental Cancer Medicine, Barts Cancer Institute-Queen Mary University of London, EC1M 6BQ - London/GB
  • 2Perlmutter Cancer Center, New York University Langone Medical Center, New York/US
  • 3Breast Cancer Center, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 4Division Of Gynecologic Oncology, University Hospital Heidelberg, 69115 - Heidelberg/DE
  • 5Department Of Medicine, PUCRS School of Medicine, Porto Alegre/BR
  • 6Nagoya City University Medical School, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 7Department Of Medical Oncology, Institut Curie, Paris, Paris/FR
  • 8Gynecological Clinical Service School Of Medicine, University of Sao Paulo, 04524-003 - Sao Paulo/BR
  • 9Internal Medicine, Seoul National University Hospital, 3080 - Seoul/KR
  • 10Medical Oncology & Internal Medicine, Florida Cancer Specialists & Research Institute, New Port Richey/US
  • 11Roche, Roche, Basel/CH
  • 12Biomarkers, Genentech, Inc., 94080 - South San Francisco/US
  • 13Medical Director, Genentech, Inc., South San Francisco/US
  • 14Clinical Science, Genentech, Inc., 94080 - South San Francisco/US
  • 15Immuno-oncology, Roche, 94080 - Basel/CH
  • 16Medical Oncology, Dana-Farber Cancer Institute, 2215 - Boston/US
  • 17Translational Breast Cancer Genomics Lab, Division Of Research, Peter MacCallum Cancer Center, 3002 - Melbourne/AU
  • 18Medicine, UPMC Hillman Cancer Center, Pittsburgh/US

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.