Rociletinib (roci) is a T790M-selective EGFR TKI. Among pts on the phase I/II TIGER-X study, we observed late-onset, quickly progressive cataracts (cats). We retrospectively contacted pts to assess the incidence of cats among pts treated at our centers, including those beyond the 30-day post-roci protocol follow-up (FU) period.
To identify pts at risk for roci-associated cats, we excluded pts with pre-existing cats or prior cat surgery, pts treated with sub-therapeutic roci doses (< 900 mg BID free base (FB), and those who lived
Of 284 pts enrolled at the participating sites through Feb 2015, 205 were at risk for cats (135 F, 70 M). The median age was 59 years (range 29-86). The median duration of roci exposure was 7.8 mos (range 0.3-29.5). Pts received starting BID roci doses of 900 mg FB (10 pts) or 500 (55), 625 (73), 750 (62) and 1000 (5) mg HBr tablets. Median FU was 10.4 mos. 69 (34%) pts developed cats; 53 (26%) required surgical repair. Among those successfully contacted for longterm FU, the rate of cats was 69/104 (66%). The median time from initial roci exposure to first cat surg was 14.0 mos (95% CI, 2.8-29.6). Roci-associated cats frequently progressed to hypermature, surgical cats in wks to mos. Surgery was often more complex than typical senile cats, with increased risk of high intralenticular pressure and need for specialized intraop techniques. Variables significantly associated with an increased risk of cat surg included hyperglycemia (p = 0.043), maximum Hgb A1c (p = 0.022), and duration of roci exposure (OR 1.25; p =
Roci is associated with a high risk (34%) of late-onset cataracts, with a median latency of 14 mos from initial drug exposure to surgery. Higher rates of cats may be observed with more complete late FU. The cats appear to have a more rapid course than typical senile cats. Delayed surgical repair may result in increased risk of intraop complications. Roci-treated pts with longterm survival should be screened for cataracts.
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Z. Piotrowska: Consulting for Clovis Oncology, AstraZeneca and Boehringer-Ingelheim. A. Varga: Consulting: AstraZeneca and Clovis Oncology. S.V. Liu: Consultant/advisory board: Genentech, Boehringer Ingelheim, Ariad, Biodesix, Caris Life Sciences. J. Neal: Consulting/Advisory role: Clovis Oncology, CARET/Physicians Resource Management, Nektar, Boehringer Ingelheim, ARMO BioSciences. Research Funding: Genentech/Roche, Merck, ArQule, Novartis, Exelixis, Boehringer Ingelheim, Nektar. B. Solomon: Consulting/Advisory Boards: Pfizer, Roche, AstraZeneca, Novartis, Clovis Oncology, Merck, BMS. H. Yu: Consulting: AstraZeneca, Boehringer-Ingelheim. Research support: Clovis Oncology, AstraZeneca, and Astellas. S-H.I. Ou: Honorarium for ad board: Roche, Boehringer Ingelheim, ARIAD, Astra Zeneca Honorarium for speaker bureau: Roche, Astra Zeneca, Boehringer Ingelheim. V.A. Papadimitrakopoulou: Advisory role: Clovis Oncology. S. Gadgeel: Consulting/Advisory Boards: Genentech/Roche, Astra-Zeneca. D.R. Camidge: Honoraria: AstraZeneca and Clovis Oncology. J-C. Soria: Consultancy fees: AstraZeneca, Astex, Covagen, Clovis, GSK, Gammamabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pierre Fabre, Roche-Genentech, Sanofi, Servier, Takeda. H. Wakelee: Research support from Clovis Oncology. J. Goldman: Honoraria: Clovis Oncology. Research funding: Clovis Oncology. L. Rolfe: Employee of Clovis Oncology. L.V. Sequist: Uncompensated consulting for Clovis, BI, Merrimack, Novartis, and Taiho and compensated consulting for AZ and Ariad. The institution received sponsored research funds from Clovis. All other authors have declared no conflicts of interest.