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.

Collapse