JTO Clinical and Research Reports (Dec 2022)
The Role of Chemotherapy Plus Immune Checkpoint Inhibitors in Oncogenic-Driven NSCLC: A University of California Lung Cancer Consortium Retrospective Study
- David J. Benjamin, MD,
- Shuai Chen, PhD,
- Joanna B. Eldredge, MD,
- Shiruyeh Schokrpur, MD,
- Debory Li,
- Zhikuan Quan, MS,
- Jason W. Chan, MD,
- Amy L. Cummings, MD,
- Megan E. Daly, MD,
- Jonathan W. Goldman, MD,
- Matthew A. Gubens, MD,
- Jeremy P. Harris, MD,
- Mark W. Onaitis, MD,
- Viola W. Zhu, MD, PhD,
- Sandip P. Patel, MD,
- Karen Kelly, MD
Affiliations
- David J. Benjamin, MD
- Divsion of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California; Present Address: 1 Hoag Drive, Building 51, Newport Beach, California
- Shuai Chen, PhD
- Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, California
- Joanna B. Eldredge, MD
- Division of Hematology and Oncology, Department of Medicine, University of California Davis School of Medicine, Sacramento, California
- Shiruyeh Schokrpur, MD
- Division of Hematology-Oncology, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
- Debory Li
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
- Zhikuan Quan, MS
- Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, California
- Jason W. Chan, MD
- Department of Radiation Oncology, University of California, San Francisco, San Francisco, California
- Amy L. Cummings, MD
- Divsion of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California; Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, California; Division of Hematology and Oncology, Department of Medicine, University of California Davis School of Medicine, Sacramento, California; Division of Hematology-Oncology, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California; Division of Hematology Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, California; Division of Hematology Oncology, Department of Medicine, University of California San Francisco, San Francisco, California; Department of Radiation Oncology, University of California Irvine, Irvine, California; Division of Cardiothoracic Surgery, Department of Surgery, University of California, San Diego, La Jolla, California; Present Address: 1 Hoag Drive, Building 51, Newport Beach, California; Present Address: Nuvalent, 1 Broadway, 14th Floor, Cambridge, Massachusetts; Present Address: 999, 17th Street, Suite 200, Denver, Colorado
- Megan E. Daly, MD
- Divsion of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California; Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, California; Division of Hematology and Oncology, Department of Medicine, University of California Davis School of Medicine, Sacramento, California; Division of Hematology-Oncology, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California; Division of Hematology Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, California; Division of Hematology Oncology, Department of Medicine, University of California San Francisco, San Francisco, California; Department of Radiation Oncology, University of California Irvine, Irvine, California; Division of Cardiothoracic Surgery, Department of Surgery, University of California, San Diego, La Jolla, California; Present Address: 1 Hoag Drive, Building 51, Newport Beach, California; Present Address: Nuvalent, 1 Broadway, 14th Floor, Cambridge, Massachusetts; Present Address: 999, 17th Street, Suite 200, Denver, Colorado
- Jonathan W. Goldman, MD
- Divsion of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California; Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, California; Division of Hematology and Oncology, Department of Medicine, University of California Davis School of Medicine, Sacramento, California; Division of Hematology-Oncology, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California; Division of Hematology Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, California; Division of Hematology Oncology, Department of Medicine, University of California San Francisco, San Francisco, California; Department of Radiation Oncology, University of California Irvine, Irvine, California; Division of Cardiothoracic Surgery, Department of Surgery, University of California, San Diego, La Jolla, California; Present Address: 1 Hoag Drive, Building 51, Newport Beach, California; Present Address: Nuvalent, 1 Broadway, 14th Floor, Cambridge, Massachusetts; Present Address: 999, 17th Street, Suite 200, Denver, Colorado
- Matthew A. Gubens, MD
- Divsion of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California; Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, California; Division of Hematology and Oncology, Department of Medicine, University of California Davis School of Medicine, Sacramento, California; Division of Hematology-Oncology, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California; Division of Hematology Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, California; Division of Hematology Oncology, Department of Medicine, University of California San Francisco, San Francisco, California; Department of Radiation Oncology, University of California Irvine, Irvine, California; Division of Cardiothoracic Surgery, Department of Surgery, University of California, San Diego, La Jolla, California; Present Address: 1 Hoag Drive, Building 51, Newport Beach, California; Present Address: Nuvalent, 1 Broadway, 14th Floor, Cambridge, Massachusetts; Present Address: 999, 17th Street, Suite 200, Denver, Colorado
- Jeremy P. Harris, MD
- Divsion of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California; Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Davis, California; Division of Hematology and Oncology, Department of Medicine, University of California Davis School of Medicine, Sacramento, California; Division of Hematology-Oncology, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California; Division of Hematology Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California; Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, California; Division of Hematology Oncology, Department of Medicine, University of California San Francisco, San Francisco, California; Department of Radiation Oncology, University of California Irvine, Irvine, California; Division of Cardiothoracic Surgery, Department of Surgery, University of California, San Diego, La Jolla, California; Present Address: 1 Hoag Drive, Building 51, Newport Beach, California; Present Address: Nuvalent, 1 Broadway, 14th Floor, Cambridge, Massachusetts; Present Address: 999, 17th Street, Suite 200, Denver, Colorado
- Mark W. Onaitis, MD
- Division of Hematology-Oncology, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
- Viola W. Zhu, MD, PhD
- Divsion of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, California; Present Address: Nuvalent, 1 Broadway, 14th Floor, Cambridge, Massachusetts
- Sandip P. Patel, MD
- Division of Hematology-Oncology, Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California
- Karen Kelly, MD
- Division of Hematology and Oncology, Department of Medicine, University of California Davis School of Medicine, Sacramento, California; Present Address: 999, 17th Street, Suite 200, Denver, Colorado; Corresponding author. Address for correspondence: Karen Kelly, MD, International Association for the Study of Lung Cancer, 999 17th Street, Suite 200, Denver, Colorado 80202-2725.
- Journal volume & issue
-
Vol. 3,
no. 12
p. 100427
Abstract
Introduction: There is a paucity of data on immune checkpoint inhibitors (ICIs) plus doublet chemotherapy (C) in patients with advanced lung cancer whose tumor harbors an actionable mutation. We sought to provide insight into the role of this combination in relation to chemotherapy alone in this patient population. Methods: We conducted a retrospective study at the five University of California National Cancer Institute–designated Comprehensive Cancer Centers. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and significant adverse events. Adverse events in patients who received a tyrosine kinase inhibitor (TKI) post-ICI were also captured. Results: A total of 246 patients were identified, 170 treated with C plus ICI and 76 treated with C alone. Driver alterations included EGFR (54.9%), KRAS (32.9%), ALK (5.3%), HER2/ERBB2 (2.9%), ROS1 (1.2%), MET (1.2%), RET (0.8%), and BRAF non-V600 (0.8%). The overall PFS and OS hazard ratios were not significant at 1.12 (95% confidence interval 0.83–1.51; p = 0.472) and 0.86 (95% confidence interval: 0.60–1.24, p = 0.429), respectively. No significant differences in PFS or OS were observed in the mutational subgroups. Grade 3 or greater adverse events were lower in the C plus ICI group. The multivariate analysis for PFS and OS revealed a performance status (Eastern Cooperative Oncology Group) score of 2, and previous TKI treatment was associated with poorer outcomes with C plus ICI. Conclusions: Our study suggests that patients with oncogenic-driven NSCLC, primarily those with EGFR-driven tumors, treated with a TKI should not subsequently receive C plus ICI. Analysis from prospective clinical trials will provide additional information on the role of ICIs in this group of patients.
