Crizotinib in advanced ROS1-rearranged non-small cell lung cancer (NSCLC): Overall survival (OS) and updated safety from PROFILE 1001
Authors: A. Shaw, G.J. Riely, Y.-J. Bang, D.-W. Kim, D.R. Camidge, G.I. Shapiro, T. Usari, S.C. Wang, K. Wilner, J.W. Clark, S.-H.I. Ou
Journal: Annals of Oncology (2019)

Background: In the ongoing phase 1 PROFILE 1001 study (NCT00585195), crizotinib provided a meaningful clinical benefit for patients (pts) with advanced ROS1-rearranged NSCLC, as evidenced by a high objective response rate (72%) and rapid, substantial and durable responses (median duration of response, 18 months [mo]); in addition, crizotinib was well-tolerated (Shaw, N Engl J Med, 2014). Here, we present OS results and updated safety (additional follow-up >3 years) in these pts. Methods: Pts with histologically confirmed NSCLC containing ROS1 rearrangements were enrolled and treated with oral crizotinib 250 mg twice daily (BID). ROS1 status was assessed by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. Results: Between October 2010 and June 2018, 53 pts with ROS1-rearranged NSCLC were treated with crizotinib; median duration of treatment was 22 mo (95% confidence interval [CI]: 15, 36). At the time of data cutoff (June 30, 2018), 12 pts (22.6%) remained on treatment. A total of 26 deaths (49.1%) occurred over a median follow-up period of 63 mo. Median OS was 51 mo (95% CI: 29, not reached) and the probabilities of survival at 12, 24 and 48 mo were 78.8%, 67.0% and 50.7%, respectively. With a median treatment duration nearly 8 mo longer than that for the primary endpoint analysis and 30.2% of patients on treatment for more than 4 years, no new safety signals were noted. The most common grade 3 treatment-related adverse events (TRAEs; in ≥ 5% of pts) were hypophosphatemia (15.1%) and neutropenia (9.4%); no grade 4 TRAEs or treatment-related deaths were reported. With longer follow-up, there were no permanent discontinuations associated with TRAEs. Conclusions: The results of the OS analysis and updated safety information from PROFILE 1001 continue to support the favorable benefit/risk profile of crizotinib 250 mg BID for the treatment of patients with advanced ROS1-positive NSCLC. Clinical trial identification: NCT00585195. Editorial acknowledgement: Editorial assistance was provided by Vasupradha Vethantham, PhD, of inScience Communications, Springer Healthcare (New York, NY, USA), with funding from Pfizer, Inc. Legal entity responsible for the study: Pfizer, Inc. Funding: Pfizer, Inc. Disclosure: A. Shaw: Fees for consulting/advisory board roles: ARIAD/Takeda, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Foundation Medicine Genentech, Ignyta, KSQ Therapeutics, Loxo, Novartis, Pfizer, Roche, Taiho; Honoraria: Novartis, Pfizer, Roche; Research funding to institution: Daiichi Sankyo, Ignyta, Novartis, Pfizer, Roche/Genentech, TP Therapeutics. Y-J. Bang: Advisory boards: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Daiich-Sankyo, Eli Lilly, GreenCross, Genentech/Roche, Hanmi, Novartis, Merck Serano, MSD, Samyang Biopharm, Taiho; Research funding to institution: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Boeringer Ingelheim, Boston Biomedical, CKD Pharma, Curis, Daiichi Sankyo, Eli Lilly, FivePrime, Glaxo Smith-Kline, Genentech/Roche, Green Cross, MacroGenics, Merck Serano, MSD, Novartis, Pfizer, Ono, Takeda, Taiho. D.R. Camidge: Advisory boards: AbbVie, ARIAD, Array, Celgene, Clovis, Eli Lilly, G1 Therapeutics (DSMB), Genoptix, Ignyta, Mersana Therapeutics, Novartis, Orion, Roche/Genentech, Takeda; Research for investigator-initiated trials: ARIAD, Takeda. G.J. Riely: Funding to institution: Pfizer for the conduct of this research; Research support to institution: Novartis, Roche, Takeda. Compensated consultant: Genentech/Roche. G.I. Shapiro: Research funding to the Dana-Farber Cancer Institute: Pfizer for the conduct of the study; Advisory boards: Eli Lilly, G1 Therapeutics, Merck/EMD Serono, Roche, Pfizer, Vertex Pharmaceuticals. T. Usari, S.C. Wang, K. Wilner: Employee, holds stock: Pfizer. J.W. Clark: Institutional research funding: Pfizer. S-H.I. Ou: Fees for consulting/Advisory board: Pfizer; Research funding to institution: Eli Lilly, Merck/EMD Serono, Pfizer. All other authors have declared no conflicts of interest.