VP2_2021 - Effectiveness of PD-(L)1 inhibitors alone or in combination with platinum-doublet chemotherapy in first-line (1L) non-squamous non-small cell lung cancer (Nsq-NSCLC) with high PD-L1 expression using real-world data

Abstract

S. Peters¹, U. Dafni², M. Perol³, E. Felip⁴, L. Polito⁵, N. Pal⁶, T.G.N. Ton⁶, D. Merritt⁷, S. Morris⁸, R.A. Stahel^9
1Multidisciplinary Oncology, Centre Hospitalier Universitaire Vaudois – CHUV, Lausanne, Switzerland; ²ETOP Statistical Center, Frontier-Science Foundation—Hellas, Athens, Greece; ³Medical Oncology, Centre Léon Bérard, Lyon, France; ⁴Medical Oncology Service (Lung Cancer Unit), Vall d'Hebron University Hospital, Barcelona, Spain; ⁵Product Development Personalized Healthcare, F. Hoffmann-La Roche, Ltd, Basel, Switzerland; ⁶Product Development Personalized Healthcare, Genentech, Inc., South San Francisco, CA, USA; ⁷Product Development Medical Affairs, F. Hoffmann-La Roche, Ltd, Basel, Switzerland; ⁸Product Development Medical Affairs Oncology, F. Hoffmann-La Roche, Ltd, Basel, Switzerland; ⁹Foundation Council, European Thoracic Oncology Platform (ETOP), Berne, Switzerland

Background: Anti−PD-(L)1 therapy alone (cancer immunotherapy [CIT]-mono) or combined with platinum-based chemotherapy (CIT-chemo) is used as 1L treatment for patients with metastatic Nsq-NSCLC with a PD-L1 tumor proportion score (TPS) ≥50% (high expression). Our study compared clinical outcomes with CIT-mono vs CIT-chemo in this specific clinical scenario.

Methods: This was a retrospective cohort study using the nationwide Flatiron Health Electronic Health Record-derived de-identified US database. Patients with metastatic Nsq-NSCLC with high PD-L1 expression initiating 1L CIT-mono or CIT-chemo between 24 Oct 2016 and 28 Feb 2019 were followed until study end (28 Feb 2020). We compared overall survival (OS) and real-world progression-free survival (rwPFS) using Kaplan-Meier methodology. Hazard ratios (HR) were adjusted (aHR) for differences in baseline characteristics.

Results: Patients with PD-L1−high Nsq-NSCLC treated with CIT-mono (n=351) had higher proportions of poor prognostic baseline characteristics (notably, age and metastatic disease type) than patients treated with CIT-chemo (n=169; Table). With a median follow-up of 19.9 mo for CIT-chemo vs 23.5 mo for CIT-mono, median OS and rwPFS did not differ between the two groups (median OS: CIT-chemo, 21.0 mo vs CIT-mono, 22.1 mo, aHR=1.03, 95% CI 0.77-1.39, P=0.83; median rwPFS: CIT-chemo, 10.8 mo vs CIT-mono, 11.5 mo, aHR=1.04, 95% CI 0.78-1.37, P=0.81). CIT-chemo only showed significant and meaningful improvement in OS and rwPFS vs CIT-mono in the never-smoker subgroup, albeit a small sample of patients (n=50; OS HR=0.25, 95% CI 0.07-0.83, interaction P=0.02; rwPFS HR=0.40, 95% CI 0.17-0.95, interaction P=0.04).

Conclusions: Except in a subgroup of patients with no smoking history, sparing the chemotherapy in 1L CIT treatment does not appear to impact survival outcomes. Table: Baseline Characteristics

Variable
Categories
CIT-chemo
CIT-mono

N
169
351

Age group, n (%)
<65 y
77 (45.6)
109 (31.1)

≥65 y
92 (54.4)
242 (68.9)

Sex, n (%)
F
75 (44.4)
183 (52.1)

M
94 (55.6)
168 (47.9)

Smoking status, n (%)
Former/current
153 (90.5)
317 (90.3)

No history
16 (9.5)
34 (9.7)

ECOG performance status, n (%)
0
77 (45.6)
138 (39.3)

1
92 (54.4)
213 (60.7)

Metastatic disease type, n (%)
De novo stage IV
157 (92.9)
271 (77.2)

Recurrent
12 (7.1)
80 (22.8)

Brain metastasis, n (%)
Yes
50 (30.0)
91 (25.9)

Liver metastasis, n (%)
Yes
28 (16.6)
43 (12.3)


Editorial acknowledgement: Medical writing support 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. Peters: Financial Interests: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Foundation Medicine, Illumina, Incyte, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merri; Financial Interests, Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, Illumina, Medscape, Merck Sharp and Dohme, Novartis, Pfizer, Prime, Roche/Genentech, Sanofi, Takeda; Financial Interests, (Sub)investigator in trials (institutional financial support for clinical trials): Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phoshoplatin Therapeutics, Roche/Genentech.
U. Dafni: Financial Interests, Advisory/Consultancy: Roche.
M. Perol: Financial Interests, Advisory/Consultancy: Roche, AstraZeneca, Lilly, Pfizer, MSD, Bristol Myers Squibb, Boehringer Ingelheim, Novartis, Sanofi, Gritstone, Illumina, Takeda; Financial Interests: Amgen, Chugai; Financial Interests: Amgen, Chugai.
E. Felip: Financial Interests, Honoraria: AbbVie, Amgen, AstraZeneca, Bayer, Blue Print Medicines, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Roche, Peervoice, Pfizer, prIME Oncology, Puma Biotechnology, Roche, Sanofi ; Financial Interests: Grant for Oncology Innovation (GOI), Fundación Merck Salud; and Office/Board of Directors for Grífols.
L. Polito: Financial Interests: Roche.
N. Pal: Financial Interests: Genentech, Inc.; Financial Interests: Roche/Genentech.
T.G.N. Ton: Financial Interests: Genentech; Financial Interests: Roche.
D. Merritt: Financial Interests: Roche; Financial Interests: Roche.
S. Morris: Financial Interests: Roche; Financial Interests: Roche.
R.A. Stahel: Financial Interests: Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, Eli Lilly, GSK, MSD, Novartis, Roche; Financial Interests: AstraZeneca, BMS, Janssen, MSD, Pfizer, Regeneron, Roche, Sandoz, Seattle Genetics, Takeda; Financial Interests, DMC: Genentech/Roche, Takeda; Financial Interests, Editor: CTR; Financial Interests, Editor in Chief: Lung Cancer; Financial Interests: AstraZeneca; Financial Interests, ETOP Study: BMS; Financial Interests, IBCSG Study: Ipsen; Financial Interests, ETOP Study, IBCSG Study: MSD; Financial Interests, IBCSG Study: Novartis; Financial Interests, IBCSG Study, ETOP Study: Pfizer; Financial Interests, IBCSG Study: Pierre Fabre; Financial Interests, ETOP Study, IBCSG Study: Roche; Financial Interests, President Foundation Council: ETOP; Financial Interests, President Foundation Council: IBCSG.