Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers
Introduction: ROS1 fusions are oncogenic drivers in 1% to 3% of NSCLCs. The activity of immune checkpoint inhibitor (ICI) monotherapy or in combination with chemotherapy (chemotherapy with ICI [chemo-ICI]) in these tumors and their immunophenotype have not been systematically described. Methods: In...
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2021-07-01
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Series: | JTO Clinical and Research Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364321000461 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Noura J. Choudhury, MD Jaime L. Schneider, MD, PhD Tejas Patil, MD Viola W. Zhu, MD, PhD Debra A. Goldman, MS Soo-Ryum Yang, MD Christina J. Falcon, MPH Andrew Do, BS Yunan Nie, MD Andrew J. Plodkowski, MD Jamie E. Chaft, MD Subba R. Digumarthy, MD Natasha Rekhtman, MD, PhD Maria E. Arcila, MD Alexia Iasonos, PhD Sai-Hong I. Ou, MD, PhD Jessica J. Lin, MD Alexander Drilon, MD |
spellingShingle |
Noura J. Choudhury, MD Jaime L. Schneider, MD, PhD Tejas Patil, MD Viola W. Zhu, MD, PhD Debra A. Goldman, MS Soo-Ryum Yang, MD Christina J. Falcon, MPH Andrew Do, BS Yunan Nie, MD Andrew J. Plodkowski, MD Jamie E. Chaft, MD Subba R. Digumarthy, MD Natasha Rekhtman, MD, PhD Maria E. Arcila, MD Alexia Iasonos, PhD Sai-Hong I. Ou, MD, PhD Jessica J. Lin, MD Alexander Drilon, MD Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers JTO Clinical and Research Reports Non–small cell lung cancer ROS1 fusion Immune checkpoint inhibitors Tumor mutational burden PD-L1 |
author_facet |
Noura J. Choudhury, MD Jaime L. Schneider, MD, PhD Tejas Patil, MD Viola W. Zhu, MD, PhD Debra A. Goldman, MS Soo-Ryum Yang, MD Christina J. Falcon, MPH Andrew Do, BS Yunan Nie, MD Andrew J. Plodkowski, MD Jamie E. Chaft, MD Subba R. Digumarthy, MD Natasha Rekhtman, MD, PhD Maria E. Arcila, MD Alexia Iasonos, PhD Sai-Hong I. Ou, MD, PhD Jessica J. Lin, MD Alexander Drilon, MD |
author_sort |
Noura J. Choudhury, MD |
title |
Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers |
title_short |
Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers |
title_full |
Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers |
title_fullStr |
Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers |
title_full_unstemmed |
Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers |
title_sort |
response to immune checkpoint inhibition as monotherapy or in combination with chemotherapy in metastatic ros1-rearranged lung cancers |
publisher |
Elsevier |
series |
JTO Clinical and Research Reports |
issn |
2666-3643 |
publishDate |
2021-07-01 |
description |
Introduction: ROS1 fusions are oncogenic drivers in 1% to 3% of NSCLCs. The activity of immune checkpoint inhibitor (ICI) monotherapy or in combination with chemotherapy (chemotherapy with ICI [chemo-ICI]) in these tumors and their immunophenotype have not been systematically described. Methods: In this multi-institutional retrospective study, tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) were evaluated in patients with ROS1-rearranged NSCLC. Time-to-treatment discontinuation (TTD) and objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) were calculated for patients treated with ICI or chemo-ICI in the metastatic setting. Results: A total of 184 patients were identified. Among 146 assessable cases, PD-L1 expression was less than 1% in 60 (41%), 1% to 49% in 35 (24%), and greater than or equal to 50% in 51 tumors (35%). Of 100 (92%) TMB-assessable tumors, 92 had less than 10 mutations per megabase. TMB was significantly lower for ROS1-rearranged tumors (n = 97) compared with tumors with EGFR (n = 1250) or KRAS alterations (n = 1653) and all other NSCLC tumors (n = 2753) evaluated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (median TMB = 2.6 versus 3.5, 7.0, and 6.1 mutations per megabase, p < 0.001). Among patients treated with ICI, median TTD was 2.1 months (95% confidence interval [CI]: 1.0–4.2 mo; n = 28) and ORR 13% (2 of 16 RECIST-assessable; 95% CI: 2%–38%). Among patients treated with chemo-ICI, median TTD was 10 months (95% CI: 4.7–14.1 mo; n = 11) and ORR 83% (5 of 6 RECIST-assessable; 95% CI: 36%–100%). There was no difference in PD-L1 expression (p = 0.91) or TMB (p = 0.83) between responders and nonresponders. Conclusions: Most ROS1-rearranged NSCLCs have low PD-L1 expression and TMB. The activity of ICI in these tumors is modest. In contrast, chemo-ICI can achieve meaningful activity. |
topic |
Non–small cell lung cancer ROS1 fusion Immune checkpoint inhibitors Tumor mutational burden PD-L1 |
url |
http://www.sciencedirect.com/science/article/pii/S2666364321000461 |
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doaj-81bc0a6f5dc849f182e47505ceaaaec12021-07-25T04:44:02ZengElsevierJTO Clinical and Research Reports2666-36432021-07-0127100187Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung CancersNoura J. Choudhury, MD0Jaime L. Schneider, MD, PhD1Tejas Patil, MD2Viola W. Zhu, MD, PhD3Debra A. Goldman, MS4Soo-Ryum Yang, MD5Christina J. Falcon, MPH6Andrew Do, BS7Yunan Nie, MD8Andrew J. Plodkowski, MD9Jamie E. Chaft, MD10Subba R. Digumarthy, MD11Natasha Rekhtman, MD, PhD12Maria E. Arcila, MD13Alexia Iasonos, PhD14Sai-Hong I. Ou, MD, PhD15Jessica J. Lin, MD16Alexander Drilon, MD17Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Massachusetts General Hospital Cancer Center, Boston, MassachusettsDepartment of Medicine, University of Colorado Anschutz Medical Center, Aurora, ColoradoDepartment of Medicine, University of California Irvine, Irvine, CaliforniaDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New YorkDruckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Massachusetts General Hospital Cancer Center, Boston, MassachusettsDepartment of Medicine, University of Colorado Anschutz Medical Center, Aurora, ColoradoDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New YorkDepartment of Radiology, Massachusetts General Hospital, Boston, MassachusettsDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, University of California Irvine, Irvine, CaliforniaDepartment of Medicine, Massachusetts General Hospital Cancer Center, Boston, MassachusettsDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York; Corresponding author. Address for correspondence: Alexander Drilon, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, 545 East 73rd Street, 22nd floor, New York, NY 10021.Introduction: ROS1 fusions are oncogenic drivers in 1% to 3% of NSCLCs. The activity of immune checkpoint inhibitor (ICI) monotherapy or in combination with chemotherapy (chemotherapy with ICI [chemo-ICI]) in these tumors and their immunophenotype have not been systematically described. Methods: In this multi-institutional retrospective study, tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) were evaluated in patients with ROS1-rearranged NSCLC. Time-to-treatment discontinuation (TTD) and objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) were calculated for patients treated with ICI or chemo-ICI in the metastatic setting. Results: A total of 184 patients were identified. Among 146 assessable cases, PD-L1 expression was less than 1% in 60 (41%), 1% to 49% in 35 (24%), and greater than or equal to 50% in 51 tumors (35%). Of 100 (92%) TMB-assessable tumors, 92 had less than 10 mutations per megabase. TMB was significantly lower for ROS1-rearranged tumors (n = 97) compared with tumors with EGFR (n = 1250) or KRAS alterations (n = 1653) and all other NSCLC tumors (n = 2753) evaluated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (median TMB = 2.6 versus 3.5, 7.0, and 6.1 mutations per megabase, p < 0.001). Among patients treated with ICI, median TTD was 2.1 months (95% confidence interval [CI]: 1.0–4.2 mo; n = 28) and ORR 13% (2 of 16 RECIST-assessable; 95% CI: 2%–38%). Among patients treated with chemo-ICI, median TTD was 10 months (95% CI: 4.7–14.1 mo; n = 11) and ORR 83% (5 of 6 RECIST-assessable; 95% CI: 36%–100%). There was no difference in PD-L1 expression (p = 0.91) or TMB (p = 0.83) between responders and nonresponders. Conclusions: Most ROS1-rearranged NSCLCs have low PD-L1 expression and TMB. The activity of ICI in these tumors is modest. In contrast, chemo-ICI can achieve meaningful activity.http://www.sciencedirect.com/science/article/pii/S2666364321000461Non–small cell lung cancerROS1 fusionImmune checkpoint inhibitorsTumor mutational burdenPD-L1 |