Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer

Gustavo Schvartsman; S Andrew Peng; Giorgios Bis; J Jack Lee; Marcelo F K Benveniste; Jianjun Zhang; Emily B Roarty; Lara Lacerda; Stephen Swisher; John V Heymach; Frank V Fossella; William N William

doi:10.1016/j.lungcan.2017.07.034

Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer

Lung Cancer. 2017 Oct:112:90-95. doi: 10.1016/j.lungcan.2017.07.034. Epub 2017 Aug 3.

Authors

Affiliations

¹ Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, Unit 463., Houston, TX, 77030, USA. Electronic address: gustavoschv@gmail.com.
² Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA. Electronic address: speng1@mdanderson.org.
³ Department of Radiology, Baylor College of Medicine, 6620 Main St, 12th Floor, Suite 1275, Houston, TX, 77030, USA. Electronic address: bis@bcm.edu.
⁴ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA. Electronic address: jjlee@mdanderson.org.
⁵ Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center. 1515 Holcombe Blvd, Room 1478, Houston, TX, 77030, USA. Electronic address: mfbenveniste@mdanderson.org.
⁶ Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX, 77030, USA. Electronic address: jzhang20@mdanderson.org.
⁷ Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX, 77030, USA. Electronic address: ecbrantley@mdanderson.org.
⁸ Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX, 77030, USA. Electronic address: LCAlvarez@mdanderson.org.
⁹ Department of Thoracic and Cardiovascular Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX, 77030, USA. Electronic address: sswisher@mdanderson.org.
¹⁰ Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX, 77030, USA. Electronic address: jheymach@mdanderson.org.
¹¹ Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX, 77030, USA. Electronic address: ffossell@mdanderson.org.
¹² Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX, 77030, USA. Electronic address: wnwillia@mdanderson.org.

PMID: 29191606
DOI: 10.1016/j.lungcan.2017.07.034

Abstract

Introduction: Exploratory analysis of clinical trials in various tumor types have demonstrated potential improvements in overall response rate (ORR) to chemotherapy after exposure to vaccine-based immunotherapy. The objective of this retrospective study was to determine if single-agent chemotherapy (3rd-line or beyond) would yield improved ORR when given after exposure to programmed death-(ligand)1 inhibitors (anti-PD1) in metastatic non-small cell lung cancer (NSCLC).

Materials and methods: We queried the Thoracic GEMINI database of MD Anderson Cancer Center for patients treated between 06/12 and 11/16 who received at least one single-agent chemotherapy as 3rd-line or beyond, following progression after platinum-based chemotherapy and anti-PD1. We evaluated efficacy outcomes to each therapy, including ORR by RECIST version 1.1, progression-free survival (PFS), and overall survival (OS).

Results: Out of 306 anti-PD1-treated patients registered in the database, 28 met eligibility criteria - 54% were male, median age was 66 years, 82% had adenocarcinoma, and 71% were former/current smokers. The anti-PD1 and single-agent chemotherapy most commonly used were nivolumab (86%) and docetaxel (50%), respectively. ORR to single-agent chemotherapy after exposure to anti-PD1 was 39% (11/28 patients, 8 confirmed). In contrast, ORR to first-line chemotherapy in this cohort was 37%. Liver metastasis was the only factor associated with response to single-agent chemotherapy on univariate analysis (p<0.05).

Conclusion: In NSCLC patients, the confirmed ORR to single-agent chemotherapy after immunotherapy exposure was higher as compared to historical data from the pre-anti-PD1 era, and approached ORR to first-line platinum-based chemotherapy. Further investigation of a possible immunotherapy-induced chemosensitization effect is warranted.

Keywords: Checkpoint inhibitors; Chemotherapy; Immunotherapy; Non-small cell lung cancer; PD-1; Response rate.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / immunology
Carcinoma, Non-Small-Cell Lung / mortality
Carcinoma, Non-Small-Cell Lung / pathology*
Female
Humans
Immunomodulation / drug effects
Immunotherapy
Lung Neoplasms / drug therapy*
Lung Neoplasms / immunology
Lung Neoplasms / mortality
Lung Neoplasms / pathology*
Male
Middle Aged
Molecular Targeted Therapy
Mutation
Neoplasm Staging
Survival Analysis
Treatment Outcome

Substances

Antineoplastic Agents, Immunological
Biomarkers, Tumor