Discussion
tumours, gastrointestinal and skin toxicity, tumour, RCC
TUMOURS, TUMOUR, RCC
This multicenter, open-label, phase 1b/2 study of ibrutinib combination therapy in patients with RCC (ibrutinib plus everolimus), GC (ibrutinib plus docetaxel), or CRC (ibrutinib plus cetuximab) demonstrated acceptable safety in patients with advanced tumours. Overall, results presented here suggest that administration of ibrutinib 840 mg orally with everolimus 10 mg in RCC, ibrutinib 560 mg with docetaxel 60 to 75 mg/mIn metastatic RCC, other combinations, such as sorafenib plus everolimus, have been tested. Nevertheless, excessive gastrointestinal and skin toxicity limited the translation of this combination to the clinical trials. As single agents, everolimus and sorafenib reported PFS of 4.9 and 5.5 months [In both the GC and CRC cohorts, 14 and 11 patients were DLT-inevaluable, suggesting a sick population overall at study entry. Nonetheless, in patients with refractory GC, ibrutinib plus docetaxel was associated with a higher ORR of (18%) relative to single-agent docetaxel (7%) but a similar 6-month PFS (29% and 26%) [The safety profiles for each of the drug combinations were generally consistent with the known safety profiles for the individual agents used in the study, suggesting no significant interaction between ibrutinib and partner agents and were as expected for patients with these advanced tumour types considering prior therapies and treatment duration. TEAEs related to companion drugs in this study were consistent with those reported previously in everolimus in RCC, [The heavily pretreated patient populations in this study may not have been the optimal contexts for evaluation of novel ibrutinib combination regimens, as evidenced by the modest efficacy observed relative to historical controls. However, the generally manageable safety profile seen across all three cohorts and the high levels of relative dose delivery of both ibrutinib and partner agents support the feasibility of the regimens studied, thereby warranting consideration of further evaluation in earlier stage settings and/or with different partner agents.