Abstract 1781MO
Background
In IMpower133, adding atezolizumab (atezo; anti–PD-L1) to carboplatin (C) + etoposide (E) for the first-line treatment (tx) of extensive-stage small cell lung cancer (ES-SCLC) led to improvements in OS and PFS vs placebo (PBO) + CE. OS benefit persists with longer follow-up. Here, we report exploratory analyses of long-term survivors (LTS) in IMpower133.
Methods
Eligible patients (pts) with tx-naive ES-SCLC received four 21-day cycles of C (AUC 5 mg • mL/min IV, day 1) + E (100 mg/m2 IV, days 1-3) with either atezo (1200 mg IV, day 1) or PBO, followed by maintenance tx with atezo or PBO until unacceptable toxicity, disease progression or loss of clinical benefit. Co-primary endpoints were investigator-assessed PFS and OS. This exploratory analysis included characterisation of LTS, defined as pts who survived ≥ 18 mo post randomisation; pts who died < 18 mo post randomisation were defined as non-LTS. Pts who were censored at < 18 mo were excluded. Association of LTS with pt and disease characteristics was explored.
Results
At data cutoff (24 Jan 2019), median follow-up in the ITT population was 22.9 mo; 373 pts were included in this exploratory analysis. There were more LTS in the atezo + CE arm (n = 61, 33.5%; 95% CI: 26.7, 40.9) than in the PBO + CE arm (n = 39, 20.4%; 95% CI: 14.9, 26.8). Among LTS, baseline categories with a > 5% difference between tx arms included age, sex, ECOG PS, LDH and brain metastases (Table). Median SLD was lower in the LTS vs the non-LTS group. Biomarker status (bTMB; PD-L1) did not appear to be associated with long-term survival benefit. Table: 1781MO
Baseline characteristics | LTS (n = 100) | Non-LTS (n = 273) | ||
Atezo + CE (n = 61) | PBO + CE (n = 39) | Atezo + CE (n = 121) | PBO + CE (n = 152) | |
Age group, n (%) | ||||
< 65 y | 31 (50.8) | 26 (66.7) | 69 (57.0) | 74 (48.7) |
≥ 65 y | 30 (49.2) | 13 (33.3) | 52 (43.0) | 78 (51.3) |
Sex, n (%) | ||||
Male | 35 (57.4) | 25 (64.1) | 81 (66.9) | 98 (64.5) |
Female | 26 (42.6) | 14 (35.9) | 40 (33.1) | 54 (35.5) |
ECOG PS, n (%) | ||||
0 | 32 (52.5) | 18 (46.2) | 35 (28.9) | 46 (30.3) |
1 | 29 (47.5) | 21 (53.8) | 86 (71.1) | 106 (69.7) |
Median SLD (range), mm | 91 (12-239) | 89 (27-208) | 122 (12-325) | 112 (15-353) |
LDH, U/L | ||||
n | 60 | 39 | 117 | 148 |
≤ ULN | 37 (61.7) | 20 (51.3) | 38 (32.5) | 61 (41.2) |
> ULN | 23 (38.3) | 19 (48.7) | 79 (67.5) | 87 (58.8) |
Brain metastases at baseline, n (%) | 4 (6.6) | 2 (5.1) | 13 (10.7) | 14 (9.2) |
Conclusions
In IMpower133, more pts in the atezo + CE arm than in the PBO + CE arm were LTS. While sample size was small, exploratory analyses suggest that pts with ES-SCLC can derive benefit from the addition of atezo to chemotherapy regardless of the pt and disease characteristics evaluated, confirming atezo + CE as standard of care for pts with untreated ES-SCLC.
Clinical trial identification
NCT02763579.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD, of Health Interactions.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
S.V. Liu: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca, Merck/MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech/Roche; Advisory/Consultancy: Boehringer Ingelheim, Janssen, Loxo, PharmaMar, Takeda; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Celgene, G1 Therapeutics, Guardant Health, Inviata; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Regeneron; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Debiopharm; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Molecular Partners; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): RAPT; Research grant/Funding (institution): Spectrum; Research grant/Funding (institution): Turning Point Therapeutics. L. Horn: Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Incyte; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Xcovery; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy: Pfizer. T. Mok: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Shareholder/Stockholder/Stock options: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche/Genentech, BMS, Boehringer Ingelheim, Novartis, MSD, Pfizer; Honoraria (self), Advisory/Consultancy: Merck Serono, Oncogenex, Ignyta Inc, Celgene, Janssen, OrigiMed, Hengrui Therapeutics, Sanofi-Aventis R&D, Yuhan Corporation, Vertex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): SFJ Pharmaceuticals; Honoraria (self), Advisory/Consultancy: ACEA Biosciences; Advisory/Consultancy: geneDecode; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy: Fishawack Facilitate Ltd; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Shareholder/Stockholder/Stock options: HutchisonChiMed; Honoraria (self), Research grant/Funding (institution): XCovery; Shareholder/Stockholder/Stock options: Sanomics; Shareholder/Stockholder/Stock options: Loxo Oncology; Honoraria (self), Speaker Bureau/Expert testimony: Amoy Diagnostics. A. Mansfield: Honoraria (institution): AbbVie; Honoraria (institution): AstraZeneca; Honoraria (institution): BMS; Honoraria (institution): Genentech/Roche; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Verily; Non-remunerated activity/ies: Mesothelioma Applied Research Foundation. R. De Boer: Honoraria (self), Advisory/Consultancy: Roche Australia; Research grant/Funding (institution): Roche. S. Sugawara: Honoraria (self): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Eli Lilly & Co.; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Kyowa Hakko Kirin. R. Dziadziuszko: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Takeda; Honoraria (self): Pfizer; Honoraria (self): SeattleGenetics; Honoraria (self): Novartis; Honoraria (self): FoundationMedicine; Honoraria (self): Merck & Co.; Honoraria (self): Merck; Honoraria (institution): CelonPharma . A. Smolin: Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Takeda; Advisory/Consultancy: BIOCAD; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: GSK. M.J. Hochmair: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Takeda. M.C. Garassino: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Tiziana Sciences, Merck, Clovis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Celgene; Honoraria (self), Research grant/Funding (institution): Otsuka Pharma; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): AstraZeneca AB; Research grant/Funding (institution): United Therapeutics Corporation; Honoraria (self), Research grant/Funding (institution): Incyte Corporation; Advisory/Consultancy, Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Exelixis Inc., GSK S.p.A; Advisory/Consultancy: Boehringer Ingelheim, Seattle Genetics, Daiichi Sankyo, Inviata, Sanofi Aventis, Janssen, GSK; Advisory/Consultancy: Blueprint Medicine; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self): MedImmune; Leadership role: Women for Oncology Italy; Leadership role: ESMO Task Forces. S. Lam: Full/Part-time employment: Genentech. M. McCleland: Full/Part-time employment: Genentech; Shareholder/Stockholder/Stock options: Roche Holdings. A. Cardona: Full/Part-time employment: Roche. S. Morris: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. M. Reck: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Samsung. All other authors have declared no conflicts of interest.
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