Response to Immune Checkpoint Inhibition as Monotherapy or in Combination With Chemotherapy in Metastatic ROS1-Rearranged Lung Cancers
| Autor: | Jessica J. Lin, Yunan Nie, Alexia Iasonos, Andrew J. Plodkowski, Maria E. Arcila, Debra A. Goldman, Jaime L. Schneider, Viola W. Zhu, Sai-Hong Ignatius Ou, Natasha Rekhtman, Alexander Drilon, Subba R. Digumarthy, Tejas Patil, Jamie E. Chaft, Christina Falcon, Andrew Do, Noura J. Choudhury, Soo-Ryum Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Oncology PD-L1 medicine.medical_specialty medicine.medical_treatment ROS1 fusion medicine.disease_cause 03 medical and health sciences Immune checkpoint inhibitors 0302 clinical medicine Immunophenotyping Internal medicine medicine ROS1 Non–small cell lung cancer RC254-282 Chemotherapy biology business.industry Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Immune checkpoint Tumor mutational burden Response Evaluation Criteria in Solid Tumors 030220 oncology & carcinogenesis biology.protein KRAS business 030215 immunology |
| Zdroj: | JTO Clinical and Research Reports, Vol 2, Iss 7, Pp 100187-(2021) |
| ISSN: | 2666-3643 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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