LEN prolonged PFS in pts with RR-DTC in SELECT. Efficacy was maintained in all subgroups. Toxicity was manageable with dose modifications, but whether a longer period of dose interruption may impact efficacy was unclear.
Pts were randomized 2:1 to receive LEN 24 mg/day or placebo. LEN-treated pts were divided into 2 groups by duration of dose interruption: <10% (A) and ≥10% (B) of total treatment duration. These were not randomized groups. PFS, ORR, and safety were analyzed in both groups.
There were 261 LEN-treated pts (A: 134, B: 127). Differences in pt characteristics between groups (A and B) were, respectively: age (>65 years, 33% and 49%), race (Asian, 10% and 25%), and ECOG PS (0, 64% and 46%). Median duration of dose interruption (range) was 19 days (0–63) and 61 days (2–266) in A and B, respectively. Median PFS was not reached (HR to placebo: 0.14; 95% CI: 0.09–0.20, P<0.001) in A and 12.8 months (HR to placebo: 0.31, 95% CI: 0.22–0.43) in group B. ORR was 76% for A and 53% for B. DCR was 88% and 87% in A and B, respectively. Common AEs were similar in both groups, but incidences (A; B) were different for diarrhea (74%; 58%), decreased appetite (45%; 62%), decreased weight (57%; 44%), PPE (27%; 38%), and proteinuria (23%; 42%). Common AEs leading to dose interruption or reduction (A; B) included diarrhea (24%; 21%), hypertension (16%; 24%), proteinuria (11%; 27%), and decreased appetite (10%; 27%).
Longer duration of dose interruption may negatively affect potential efficacy of LEN. Management of toxicities is essential to avoid long dose interruption. Differences in pt characteristics may confound the results. However, in this analysis, LEN achieved improved PFS and ORR vs placebo, regardless of length of dose interruption.