IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or witho...

Date 22 October 2018
Event ESMO 2018 Congress
Session Proffered paper session- NSCLC, metastatic
Topics Anticancer Agents
Immunotherapy
Presenter Federico Cappuzzo
Authors F. Cappuzzo1, M. McCleod2, M. Hussein3, A. Morabito4, A. Rittmeyer5, H.J. Conter6, H. Kopp7, D. Daniel8, S. McCune9, T. Mekhail10, A. Zer11, N. Reinmuth12, A. Sadiq13, V. Archer14, T. Ochi Lohmann15, L. Wang16, M. Kowanetz17, W. Lin18, A. Sandler19, H. West20
  • 1Dipartimento Di Oncologia Medica, Azienda Unità Sanitaria Locale della Romagna, 48100 - Ravenna/IT
  • 2Sarah Cannon Research Institute, Florida Cancer Specialists, Fort Myers/US
  • 3Sarah Cannon Research Institute, Florida Cancer Specialists, Leesburg/US
  • 4Thoracic Medical Oncology, Istituto Nazionale Tumori, IRCCS “Fondazione G. Pascale”, Naples/IT
  • 5Department Of Thoracic Oncology, Lungenfachklinik Immenhausen, Immenhausen/DE
  • 6Department Of Medicine, William Osler Health System, Ontario/CA
  • 7Robert Bosch Centrum Für Tumorerkrankungen (rbct), Klinik Schillerhöhe, Stuttgart/DE
  • 8Medical Oncology, Tennessee Oncology, Chattanooga/US
  • 9Northwest Georgia Oncology Centers, Marietta Cancer Center, Marietta/US
  • 10Medical Oncology, Florida Hospital Cancer Institute, Orlando/US
  • 11Thoracic Oncology Unit, Rabin Medical Center, Tel Aviv University, Tel Aviv/IL
  • 12Thoracic Oncology, Asklepios Clinics Munich-Gauting, Gauting/DE
  • 13Fort Wayne Medical, Oncology and Haematology, Fort Wayne/US
  • 14Pd Oncology, Roche Products Limited, Welwyn Garden City/GB
  • 15Pd Oncology, F. Hoffmann-La Roche Ltd, Basel/CH
  • 16Biostatistics, Genentech Inc, South San Francisco/US
  • 17Oncology Biomarker Development, Genentech Inc, 94080 - South San Francisco/US
  • 18Clincial Science, Genentech, Inc, South San Francisco/US
  • 19Clinical Science, Genentech Inc, 94080 - South San Francisco/US
  • 20Thoracic Oncology Program, Swedish Cancer Institute, Seattle/US

Abstract

Background

Atezo (anti-PD-L1) monotherapy improves overall survival (OS) vs docetaxel in 2L+ NSCLC, regardless of PD-L1 status; phase 3, 1L studies have shown the clinical benefit of atezo plus chemotherapy. IMpower130 (NCT02367781) evaluated atezo + CnP vs CnP in patients (pts) with measurable (RECIST v1.1) stage IV non-squamous NSCLC.

Methods

Pts (randomised 2:1) received atezo (1200 mg IV q3w) + CnP (carboplatin: AUC 6 q3w; nab-paclitaxel: 100 mg/m2 IV qw) (Arm A) or CnP (Arm B), for 4 or 6 21-day cycles and maintenance (Arm A: atezo until loss of clinical benefit; Arm B: best supportive care or pemetrexed q3w until disease progression [PD]). Crossover to atezo at PD was initially permitted for Arm B pts. Co-primary endpoints: investigator-assessed PFS and OS (ITT-WT population: EGFR-WT/ALK-negative). Secondary endpoints: OS and PFS (ITT population and by PD-L1 expression), response rate and safety. ITT population could be formally tested for OS/PFS if ITT-WT OS was positive.

Results

723 ITT (679 ITT-WT) pts were enrolled. Statistically significant, clinically meaningful improvements in OS and statistically significant improvements in PFS (ITT and ITT-WT) were observed in Arm A vs Arm B (table). PFS and OS benefit was observed in all PD-L1 subgroups, and consistently across all subgroups, except in pts with liver metastases and EGFR/ALK genomic alterations. In treated pts, 73.2% (Arm A) vs 60.3% (Arm B) had grade 3–4 treatment-related adverse events.

Table. IMpower130 Efficacy Analyses

Arm A
Atezo + CnP

Arm B
CnP

ITT-WT

n=451

n=228

Median OS (95% CI)

18.6 mo (16.0–21.2)

13.9 mo (12.0–18.7)

HR (95% CI; P value)

0.79 (0.64–0.98; 0.033)

12-mo OS (95% CI)

63.1% (58.59–67.66)

55.5% (48.89–62.17)

Median PFS (95% CI)

7.0 mo (6.2–7.3)

5.5 mo (4.4–5.9)

HR (95% CI; P value)

0.64 (0.54–0.77; <0.0001)

12-mo PFS (95% CI)

29.1% (24.83–33.44)

14.1% (9.37–18.76)

n=447

n=226

Confirmed ORR (investigator assessed) (95% CI)

49.2% (44.49–53.96)

31.9% (25.84–38.36)

n=220

n=72

Median DOR (95% CI)

8.4 mo (6.9–11.8)

6.1 mo (5.5–7.9)

PD-L1 higha

n=88

n=42

Median OS (95% CI)

17.4 mo (14.78–NA)

16.9 mo (10.94–NA)

HR (95% CI)

0.84 (0.51–1.39)

Median PFS (95% CI)

6.4 mo (5.49–9.76)

4.6 mo (3.22–7)

HR (95% CI)

0.51 (0.34–0.77)

PD-L1 lowa

n=128

n=65

Median OS (95% CI)

23.7 mo (18.63–NA)

15.9 mo (12.32–25.63)

HR (95% CI)

0.70 (0.45–1.08)

Median PFS (95% CI)

8.3 mo (7.16–10.35)

6.0 mo (5.29–6.93)

HR (95% CI)

0.61 (0.43–0.85)

PD-L1 negativea

n=235

n=121

Median OS (95% CI)

15.2 mo (12.88–19.15)

12.0 mo (8.97–17.71)

HR (95% CI)

0.81 (0.61–1.08)

Median PFS (95% CI)

6.2 mo (5.52–7.16)

4.7 mo (4.11–5.72)

HR (95% CI)

0.72 (0.56–0.91)

ITT

n=483

n=240

Median OS (95% CI)

18.1 mo (15.3–20.8)

13.9 mo (12.0–18.2)

HR (95% CI; P value)

0.80 (0.65–0.99; 0.039)

Median PFS (95% CI)

7.0 mo (6.3–7.3)

5.6 mo (4.5–5.9)

HR (95% CI; P value)

0.65 (0.54–0.77; <0.0001)

a PD-L1 high (TC3 or IC3): Patients with PD-L1 expression in ≥50% of tumour cells or ≥10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in ≥1% and <50% of tumour cells or ≥1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in <1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781.

DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells.

Conclusions

Overall, IMpower130 showed statistically significant, clinically meaningful improvements in OS and statistically significant improvements in PFS with atezo + CnP, vs CnP, in 1L, stage IV non-squamous NSCLC, in this predominantly ITT-WT population. No new safety signals were identified.

Clinical trial identification

NCT02367781 (20 February 2015).

Editorial Acknowledgement

Support for third-party writing assistance for this abstract, furnished by Islay Steele, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.