Pemetrexed-containing regimens should be considered in patients with RET-rearranged lung cancers, according to a study published in the Annals of Oncology.1

Previous studies have shown clinical benefit with pemetrexed-based therapies in ALK– and ROS1-rearranged cancers, but the efficacy of pemetrexed-based treatments in patients with RET-rearranged lung cancers had not been established.

Therefore, investigators conducted a retrospective review of patients with stage 3b/4 lung adenocarcinomas with RET, ROS1, or ALK rearrangement, or KRAS mutation treated with pemetrexed alone or in combination. The primary endpoint was progression-free survival (PFS), and secondary endpoints included time to progression. Time to treatment discontinuation were compared among RET-rearranged and groups of ROS1-rearranged, ALK-rearranged, and KRAS-mutant lung cancer types.

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A total of 104 patients were evaluated. Those with RET-rearranged lung cancers (n = 18) had a median PFS of 19 months (95% CI, 12 – not reached); patients with ROS1-rearrangements (n = 10) had a median PFS of 23 months (95% CI, 14 – not reached); and patients with ALK-rearrangements (n = 36) had a median PFS of 19 months (95% CI, 15 – 36). Patients with KRAS mutations (n = 40) had a median PFS of 6 months (95% CI, 5 – 9; P< .001).

Patients with RET-rearranged lung cancers did not have significantly different overall response rate, median time to progression, and median time to treatment discontinuation than those with ALK– or ROS1-rearrangement cancers, but were improved compared with those with KRAS-mutant lung cancers.

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“Durable benefits with pemetrexed-based therapies in RET-rearranged lung cancers are comparable to ALK– and ROS1-rearranged lung cancers,” the authors concluded.


  1. Drilon A, Bergagnini I, Delasos L, et al. Clinical outcomes with pemetrexed-based systemic therapies in RET-rearranged lung cancers [published online ahead of print April 7, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw163.