Response to immune checkpoint inhibition as monotherapy or in combination with chemotherapy in metastatic ROS1-rearranged lung cancers Journal Article
| Authors: | Choudhury, N. J.; Schneider, J. L.; Patil, T.; Zhu, V. W.; Goldman, D. A.; Yang, S. R.; Falcon, C. J.; Do, A.; Nie, Y.; Plodkowski, A. J.; Chaft, J. E.; Digumarthy, S. R.; Rekhtman, N.; Arcila, M. E.; Iasonos, A.; Ou, S. H. I.; Lin, J. J.; Drilon, A. |
| Article Title: | Response to immune checkpoint inhibition as monotherapy or in combination with chemotherapy in metastatic ROS1-rearranged lung cancers |
| Abstract: | 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. © 2021 The Authors |
| Keywords: | pd-l1; immune checkpoint inhibitors; non–small cell lung cancer; tumor mutational burden; ros1 fusion |
| Journal Title: | JTO Clinical and Research Reports |
| Volume: | 2 |
| Issue: | 7 |
| ISSN: | 2666-3643 |
| Publisher: | Elsevier BV |
| Date Published: | 2021-07-01 |
| Start Page: | 100187 |
| Language: | English |
| DOI: | 10.1016/j.jtocrr.2021.100187 |
| PROVIDER: | scopus |
| PMCID: | PMC8474494 |
| PUBMED: | 34590036 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2022 -- Source: Scopus |
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