Background: The question regarding the benefit of a TKI rechallenge versus switch to an mTOR inhibitor (mTORi) in mRCC pts who responded to a previous line of TKI remains unanswered and is a common dilemma in clinical practice. We report results of a retrospective study to address this question.
Methods: This study retrospectively investigated Duration of Treatment (DT), best radiological response (OR) and predictive factors in pts treated with either TKI-TKI or TKI-mTORi sequences for clear-cell mRCC. Eligibility criteria: 1 TKI in 1 st line (L1) followed by another TKI or mTORi as 2 nd line (L2). Prior immunotherapy was allowed but not intermediate lines with other drugs. Pts characteristics and Heng’s prognostic factors were collected at each line initiation. Response (resp) was classified with regard to DT and OR using 2 different definitions: def1 = Non Responders (NR): < 4months (m) + PD; Short-Term responders (STR): [4–6]m + SD/PR, Long-term Responders (LTR): >6m + SD/PR, and def2 = NR: < 4m + PD, STR: [4–12]m + SD/PR, LTR: >12m + SD/PR.
Results: 127 pts from 7 European centers were retrospectively analyzed. Based on def1, resp to L1 was: LTR=93, STR=20, NR=14; among LTR pts, 54 received a L2=TKI and 39 a L2=mTORi. Based on def2, resp to L1 was: LTR=59, STR=53, NR=15; among LTR pts, 35 received a L2=TKI and 24 a L2=mTORi. Whether def1 or def2, resp (L1 and L2) was never related to Heng’s score. Among LTR pts at L1, 26 out of 54 were LTR after L2=TKI vs 18 out of 39 after L2=mTORi (p=0.85, Z-test) for def1 and 9 out of 35 were LTR after L2=TKI vs 6 out of 24 after L2=mTORi (p=0.95) for def2 (see table). For both def1 and def2, median DT was 7.2m and 6.9m for L2=TKI and L2=mTORi, respectively (p=0.86 and p=0.95, Log-Rank).
Conclusions: Results suggest that long-term responders on 1 st line TKI could benefit both from TKI and mTORi as 2 nd line and there is no evidence to favor one sequence over the other.
[Table: see text]