Format

Send to

Choose Destination
J Thorac Oncol. 2019 Jan 18. pii: S1556-0864(19)30025-5. doi: 10.1016/j.jtho.2019.01.008. [Epub ahead of print]

A Randomized Non-Comparative Phase 2 Study of Anti-Programmed Cell Death-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients with Small Cell Lung Cancer: Results from the IFCT-1603 Trial.

Author information

1
Department of Thoracic Oncology, Montpellier Regional University Hospital, 34295 Montpellier, France. Electronic address: jl-pujol@chu-montpellier.fr.
2
Department of Multidisciplinary Oncology and Therapeutic Innovations, Assistance Publique - Hôpitaux de Marseille, Aix Marseille University, Marseille, France.
3
Department of Thoracic Oncology 54 Rue Henri Sainte Claire Deville. CHITS CH SAINTE MUSSE, 83000 Toulon.
4
Thoracic Oncology Unit , CHU Grenoble Alpes, Grenoble.
5
Institut de Cancerologie de Lorraine Alexis Vautrin. 6 Avenue de Bourgogne - 54519 Vandoeuvre-les-Nancy Cedex.
6
Pôle Hippocrate, Angers University Hospital, Angers, France.
7
Service de Pneumologie, oncologie thoracique et soins intensifs respiratoires; CHU de Rouen; 1 Rue de Germont; 76031 ROUEN CEDEX; France.
8
Service de pneumologie CHRU Hôpitaux de Tours, Hôpital Bretonneau. 2 Boulevard Tonnellé, 37000 Tours.
9
Service de pneumologie. CHU Caen Normandie. av de la Côte de Nacre, CS 30001, 14033 CAEN CEDEX 9.
10
Pôle Médecine, Centre Antoine Lacassagne. 33 Avenue de Valombrose. 06189 Nice Cedex 2.
11
Department of Thoracic Oncology, Bichat Claude Bernard Hospital, Paris, France.
12
Service de pneumologie: 58 Rue Montalembert (CHU G. MONTPIED), 63000 Clermont Ferrand.
13
Clinique des cèdres. Château Alliez, 31700 Cornebarrieu.
14
Service de pneumologie, 194 Avenue Rubillard (CENTRE HOSPITALIER DU MANS), 72000 Le Mans.
15
Servi ce de pneumologie. CENTRE HOSPITALIER DE PAU 4 boulevard Hauterive 64000 PAU.
16
Toulouse University Hospital, Université Paul Sabatier, Toulouse, France.
17
Service d'anatomo-pathologie. 4 Rue De La Chine Hôpitaux Universitaires Est Parisien Site Tenon APHP), 75020 Paris.
18
Department of Biochemistry, Nantes University Hospital, 9 quai Moncousu, F-44093 Nantes Cedex, France.
19
Department of radiology, Montpellier Regional University Hospital, 34295 Montpellier, France.
20
IFCT. Intergroupe Francophone de Cancérologie Thoracique. 10 Rue de la Grange Batelière. 75009 Paris.
21
Service de pneumologie aiguë spécialisée et cancérologie thoracique. Centre hospitalier Lyon Sud. 165 Chemin du Grand Revoyet; 69495 PIERRE-BENITE.

Abstract

INTRODUCTION:

This randomized phase 2 trial aimed at evaluating the engineered programmed cell death-ligand 1 (PD-L1) antibody atezolizumab in small cell lung cancer progressing after first-line platinum-etoposide chemotherapy.

METHODS:

Patients were randomized 2:1 to atezolizumab (1200mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to six cycles of topotecan or re-induction of initial chemotherapy). Patients were not selected based on PD-L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two-stage design with 2:1 randomization and O'Brien-Fleming stopping rules was employed. The null hypothesis was rejected if > 12/45 patients were responders.

RESULTS:

Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% CI 0.0; 6.8), while 8 others had stable disease (20.9% disease control rate; CI 8.8 ; 33.1). Among eligible chemotherapy patients (n=20), 10% achieved an objective response (65% disease control rate). Median pProgression-free survival was 1.4 months (CI 1.2; 1.5) with atezolizumab and 4.3 months (CI: 1.5; 5.9) with chemotherapy. Overall survival did not significantly differ between groups: median OS: 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively; (adjusted HRatezolizumab = 0.84 CI: 0.45 ;1.58) ; p=0.60. Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD-L1 staining (SP142 clone).

CONCLUSIONS:

Atezolizumab monotherapy in relapsed small cell lung cancer failed to demonstrate significant efficacy. No unexpected safety concerns were observed.

KEYWORDS:

atezolizumab; chemotherapy; programmed cell death-ligand 1; small cell lung cancer

PMID:
30664989
DOI:
10.1016/j.jtho.2019.01.008

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center