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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 shown durable 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%), median 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 RET-rearranged lung cancers, pemetrexed-containing regimens should be considered.

SUBMITTER: Drilon A 

PROVIDER: S-EPMC4922319 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers.

Drilon A A   Bergagnini I I   Delasos L L   Sabari J J   Woo K M KM   Plodkowski A A   Wang L L   Hellmann M D MD   Joubert P P   Sima C S CS   Smith R R   Somwar R R   Rekhtman N N   Ladanyi M M   Riely G J GJ   Kris M G MG  

Annals of oncology : official journal of the European Society for Medical Oncology 20160407 7


<h4>Background</h4>RET rearrangements are targetable, oncogenic lung cancer drivers. While previous series have shown durable 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.<h4>Patients and methods</h4>A retrospective review of patients with pathologically confirmed stage IIIB/IV lung adenocarcinom  ...[more]

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