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Mini Oral - Non-metastatic NSCLC and other thoracic malignancies

1781MO - IMpower133: Characterisation of long-term survivors treated first-line with chemotherapy ± atezolizumab in extensive-stage small cell lung cancer

Date

18 Sep 2020

Session

Mini Oral - Non-metastatic NSCLC and other thoracic malignancies

Topics

Cytotoxic Therapy;  Immunotherapy

Tumour Site

Small Cell Lung Cancer

Presenters

Stephen Liu

Citation

Annals of Oncology (2020) 31 (suppl_4): S974-S987. 10.1016/annonc/annonc290

Authors

S.V. Liu1, L. Horn2, T. Mok3, A. Mansfield4, R. De Boer5, G. Losonczy6, S. Sugawara7, R. Dziadziuszko8, M. Krzakowski9, A. Smolin10, M.J. Hochmair11, M.C. Garassino12, S. Lam13, M. McCleland14, A. Cardona15, S. Morris16, M. Reck17

Author affiliations

  • 1 Lombardi Comprehensive Cancer Center, Georgetown University, 20057 - Washington/US
  • 2 Department Of Hematology Oncology, Vanderbilt University Medical Center, Nashville/US
  • 3 State Key Laboratory Of Translational Oncology, The Chinese University of Hong Kong, Hong Kong/CN
  • 4 Division Of Medical Oncology, Mayo Clinic, Rochester/US
  • 5 Department Of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne/AU
  • 6 Department Of Pulmonology, Semmelweis University, Budapest/HU
  • 7 Department Of Pulmonary Medicine, Sendai Kousei Hospital, Sendai/JP
  • 8 Department Of Oncology And Radiotherapy, Medical University of Gdańsk, Gdańsk/PL
  • 9 Lung Cancer & Thoracic Tumours Department, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw/PL
  • 10 Department Of Radiology, Burdenko Main Military Clinical Hospital, Moscow/RU
  • 11 Department Of Respiratory And Critical Care Medicine, Karl Landsteiner Institute of Lung Research & Pulmonary Oncology, Krankenhaus, Nord, Vienna/AT
  • 12 Thoracic Oncology Unit, Division Of Medical Oncology, Foundation IRCCS-Italian National Cancer Institute, Milan/IT
  • 13 Product Development Oncology, Genentech Inc., South San Francisco/US
  • 14 Oncology Biomarker Development, Genentech Inc., South San Francisco/US
  • 15 Biometrics, F. Hoffmann-La Roche, Ltd., Basel/CH
  • 16 Global Product Development Medical Affairs (oncology), F. Hoffmann-La Roche, Ltd., Basel/CH
  • 17 Lungenclinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf/DE

Resources

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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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