Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers Journal Article
| Authors: | Drilon, A.; Bergagnini, I.; Delasos, L.; Sabari, J.; Woo, K. M.; Plodkowski, A.; Wang, L.; Hellmann, M. D.; Joubert, P.; Sima, C. S.; Smith, R.; Somwar, R.; Rekhtman, N.; Ladanyi, M.; Riely, G. J.; Kris, M. G. |
| Article Title: | Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers |
| Abstract: | Background: RET rearrangements are targetable, oncogenic lung cancer drivers. While previous series have showndurable clinical benefit with pemetrexed-based therapies in ALK- and ROS1-rearranged lung cancers, the benefits of pemetrexed-based treatments in patients with RET-rearranged lung cancers relative to other genomic subsets have not previously been explored. Patients and methods: A retrospective review of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas and evidence of a RET, ROS1, or ALK rearrangement, or a KRAS mutation was conducted. Patients were eligible if they received treatment with pemetrexed alone or in combination. The primary outcome of progression-free survival (PFS), and secondary outcomes of overall response rate (ORR, RECIST v1.1), time to progression (TTP), and time to treatment discontinuation were compared between RET-rearranged and groups of ROS1-rearranged, ALK-rearranged, and KRAS-mutant lung cancers. Results: We evaluated 104 patients. Patients with RET-rearranged lung cancers (n = 18) had a median PFS of 19 months [95% confidence interval (CI) 12-not reached (NR)] that was comparable with patients with ROS1- (23 months, 95% CI 14-NR, n = 10) and ALK-rearranged (19 months, 95% CI 15-36, n = 36) lung cancers, and significantly improved compared with patients with KRAS-mutant lung cancers (6 months, 95% CI 5-9, P <0.001, n = 40). ORR (45%), media TTP (20 months, 95% CI 17-NR), and median time to treatment discontinuation (21 months, 95% CI 6-NR) in patients with RET-rearranged lung cancers were not significantly different compared with patients with ALK- and ROS1-rearranged lung cancers, and improved compared with patients with KRAS-mutant lung cancers. Conclusion: Durable benefits with pemetrexed-based therapies in RET-rearranged lung cancers are comparable with ALK- and ROS1-rearranged lung cancers. When selecting therapies for patients with RETrearranged lung cancers, pemetrexed-containing regimens should be considered. © The Author 2016. |
| Keywords: | pemetrexed; non-small-cell lung cancer; ret rearrangement |
| Journal Title: | Annals of Oncology |
| Volume: | 27 |
| Issue: | 7 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2016-07-01 |
| Start Page: | 1286 |
| End Page: | 1291 |
| Language: | English |
| DOI: | 10.1093/annonc/mdw163 |
| PROVIDER: | scopus |
| PMCID: | PMC4922319 |
| PUBMED: | 27056998 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2016 -- Source: Scopus |
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