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Sorafenib dose escalation in treatment‐naïve patients with metastatic renal cell carcinoma: a non‐randomised, open‐label, Phase 2b study
Author(s) -
Gore Martin E.,
Jones Robert J.,
Ravaud Alain,
Kuczyk Markus,
Demkow Tomasz,
Bearz Alessandra,
Shapiro JoAnn,
Strauss Uwe Phillip,
Porta Camillo
Publication year - 2017
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.13740
Subject(s) - medicine , sorafenib , renal cell carcinoma , clinical endpoint , adverse effect , population , confidence interval , phases of clinical research , oncology , clinical trial , surgery , gastroenterology , urology , hepatocellular carcinoma , environmental health
Objective To assess the efficacy and safety of sorafenib dose escalation in metastatic renal cell carcinoma ( mRCC ). Patients and Methods Intra‐patient dose escalation may enhance the clinical benefit of targeted anticancer agents in metastatic disease. In this non‐randomised, open‐label, Phase 2b study, treatment‐naïve patients with mRCC were initially treated with the standard oral sorafenib dose [400 mg twice daily ( BID )]. Two dose escalations were planned, each 200 mg BID after 28 days at the prior level. Dose reductions, interruptions, or delayed escalations were used to manage adverse events ( AE s). The primary endpoint was objective response rate ( ORR ) in the modified intent‐to‐treat ( mITT ) population, which comprised patients with ≥6 months of treatment including ≥4 months of therapy at their highest tolerated dose. Secondary endpoints included progression‐free survival ( PFS ) and safety. Results In all, 83 patients received sorafenib. The dose received for the longest duration was 400, 600, and 800 mg BID in 48.2%, 15.7%, and 24.1% of patients, respectively. The ORR was 44.4% [ n = 8/18; 95% confidence interval ( CI ) 21.5–69.2] and 17.9% ( n = 12/67; 95% CI 9.6–29.2) in the mITT and ITT populations, respectively. The median (95% CI ) PFS was 7.4 (6.0–11.7) months ( ITT ). The most common AE s of any grade were hand–foot skin reaction (66.3%) and diarrhoea (63.9%). Conclusion Sorafenib demonstrated clinical benefit in treatment‐naïve patients with mRCC . However, relatively few patients could sustain doses of >400 mg BID . There was evidence that, where tolerated, escalation from the standard sorafenib dose may have enhanced clinical benefit. However, this study does not support dose escalation for most patients with treatment‐naïve mRCC . Alternative protocols for sorafenib dose escalation could be explored.