Efficacy of platinum/pemetrexed combination chemotherapy in ALK-positive NSCLC refractory to second-generation ALK inhibitors Journal Article
| Authors: | Lin, J. J.; Schoenfeld, A. J.; Zhu, V. W.; Yeap, B. Y.; Chin, E.; Rooney, M.; Plodkowski, A. J.; Digumarthy, S. R.; Dagogo-Jack, I.; Gainor, J. F.; Ou, S. H. I.; Riely, G. J.; Shaw, A. T. |
| Article Title: | Efficacy of platinum/pemetrexed combination chemotherapy in ALK-positive NSCLC refractory to second-generation ALK inhibitors |
| Abstract: | Introduction: The current standard initial therapy for advanced ALK receptor tyrosine kinase (ALK)–positive NSCLC is a second-generation ALK tyrosine kinase inhibitor (TKI) such as alectinib. The optimal next-line therapy after failure of a second-generation ALK TKI remains to be established; however, standard options include the third-generation ALK TKI lorlatinib or platinum/pemetrexed-based chemotherapy. The efficacy of platinum/pemetrexed-based chemotherapy has not been evaluated in cases that are refractory to second-generation TKIs. Methods: This was a retrospective study performed at three institutions. Patients were eligible if they had advanced ALK-positive NSCLC refractory to one or more second-generation ALK TKI(s) and had received platinum/pemetrexed-based chemotherapy. Results: Among 58 patients eligible for this study, 37 had scans evaluable for response with measurable disease at baseline. The confirmed objective response rate to platinum/pemetrexed-based chemotherapy was 29.7% (11 of 37 patients; 95% confidence interval [CI]: 15.9% – 47.0%), with median duration of response of 6.4 months (95% CI: 1.6 months – not reached). The median progression-free survival for the entire cohort was 4.3 months (95% CI: 2.9 – 5.8 months). Progression-free survival was longer in patients who received platinum/pemetrexed in combination with an ALK TKI compared to those who received platinum/pemetrexed alone (6.8 months vs. 3.2 months, respectively; hazard ratio = 0.33; p = 0.025). Conclusions: Platinum/pemetrexed-based chemotherapy shows modest efficacy in ALK-positive NSCLC after failure of second-generation ALK TKIs. The activity may be higher if administered with an ALK TKI, suggesting a potential role for continued ALK inhibition. © 2019 International Association for the Study of Lung Cancer |
| Keywords: | adult; cancer survival; human tissue; aged; unclassified drug; major clinical study; bevacizumab; advanced cancer; cancer combination chemotherapy; drug efficacy; adjuvant therapy; chemotherapy; antineoplastic agent; progression free survival; multiple cycle treatment; cohort analysis; retrospective study; protein tyrosine kinase inhibitor; survival time; lung adenocarcinoma; platinum; pemetrexed; alk; non small cell lung cancer; anaplastic lymphoma kinase; efficacy; nsclc; crizotinib; mitogen activated protein kinase kinase inhibitor; receptor blocking agent; human; male; female; priority journal; article; ceritinib; alectinib; luminespib; anaplastic lymphoma kinase inhibitor; brigatinib; lorlatinib; programmed death 1 receptor inhibitor; treatment response time |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 15 |
| Issue: | 2 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2020-02-01 |
| Start Page: | 258 |
| End Page: | 265 |
| Language: | English |
| DOI: | 10.1016/j.jtho.2019.10.014 |
| PUBMED: | 31669591 |
| PROVIDER: | scopus |
| PMCID: | PMC7058505 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2020 -- Source: Scopus |
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