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Fifty patients in an expansion cohort defined ROS1 as the second treatable fusion in lung cancer and put crizotinib on the label for it.
ROS1 rearrangements occur in about 1 to 2 percent of non-small-cell lung cancers, most often in younger never-smokers with adenocarcinoma. Crizotinib inhibits ALK, ROS1 and MET, and the kinase domains of ALK and ROS1 are close enough that the same molecule fits both. Fifty patients with ROS1-positive advanced disease were enrolled in an expansion cohort of the phase 1 crizotinib study and treated at the standard 250 mg twice daily.
The objective response rate was 72 percent (95 percent confidence interval 58 to 84) with three complete and 33 partial responses; median duration of response was 17.6 months and median progression-free survival 19.2 months, with half the patients still in follow-up for progression at the report. Seven ROS1 fusion partners were identified among 30 tumours tested, five known and two new, and the partner did not predict response. Safety matched the ALK experience.
The FDA added ROS1-positive metastatic non-small-cell lung cancer to the crizotinib label in 2016 on this cohort. NICE TA1021 (4 December 2024) recommends crizotinib for ROS1-positive advanced disease in England. Crizotinib has since been overtaken by entrectinib and repotrectinib, which cross into the brain and, in repotrectinib's case, cover the ROS1 G2032R solvent-front mutation.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
50 treated.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Objective response rateprimary | Crizotinib | 50 | 72% | - | - | link |
| Progression-free survival | Crizotinib | 50 | 19.2 months | - | - | link |
Shares Repotrectinib, ROS1-positive non-small-cell lung cancer, Crizotinib, Small-molecule kinase inhibitors.
Shares A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements, Repotrectinib, ROS1-positive non-small-cell lung cancer.
Shares Repotrectinib, ROS1, Tyrosine kinase inhibitor (TKI), Entrectinib.
Shares Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangeme, Entrectinib, ROS1-positive non-small-cell lung cancer.
Shares Entrectinib, ROS1-positive non-small-cell lung cancer, Crizotinib, Small-molecule kinase inhibitors.
Shares Tyrosine kinase inhibitor (TKI), Oncogene addiction, Crizotinib, Gene fusion.
Shares Repotrectinib, ROS1, ROS1-positive non-small-cell lung cancer, Small-molecule kinase inhibitors.
Shares ROS1, Entrectinib, Oncogene addiction, Crizotinib.