Sorafenib rechallenge in patients with metastatic renal cell carcinoma

Abstract

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Targeted agents with a similar or different target molecule are often used sequentially in the treatment of metastatic RCC. Two tyrosine kinase inhibitors, sorafenib and sunitinib, have been reported to show little cross‐resistance, when used sequentially. In addition, a recent report showed that sunitinib rechallenge could potentially benefit selected patients. This case series shows that patients once refractory to sorafenib could regain disease control on rechallenge with sorafenib during sequential treatment. Outcomes of the sorafenib rechallenge were not significantly affected by the response to the initial sorafenib treatment or by the duration of intervening treatments between first sorafenib and rechallenge. OBJECTIVE To investigate clinical outcomes of sorafenib rechallenge during sequential therapy for patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS Patients with metastatic RCC who received sorafenib rechallenge after failed treatment first with sorafenib and subsequently with other agents, were retrospectively reviewed for patient characteristics, best response, progression‐free survival (PFS), and adverse events (AEs). RESULTS Of the 14 patients who received sorafenib rechallenge, 12 were evaluable for response. Eleven patients had previously undergone nephrectomy, and 10 had previously received systemic therapy, mostly interferon‐α (nine patients) and interleukin‐2 (six patients), with a median duration of 9 months. The best responses after the first sorafenib therapy were partial response (PR) in two patients, stable disease (SD) in seven, and progressive disease (PD) in two. The median PFS was 5.7 months. Initial sorafenib therapy was discontinued because of PD in eight patients and AEs in four patients. Rechallenge with sorafenib was undertaken after a 7.6 month median interval from the initial sorafenib challenge. Eight patients achieved SD on sorafenib rechallenge and median PFS was 5.4 (95% confidence interval, 3.8–7.0) months. The outcome of the sorafenib rechallenge was not significantly affected by the response to the initial sorafenib treatment or by the duration of treatments received between first sorafenib and rechallenge. No severe AE was newly observed on the rechallenge. CONCLUSION In the systemic treatment of advanced RCC, it was suggested that patients once refractory to sorafenib could regain disease control on rechallenge with sorafenib during sequential treatment.

Regional Differences in Efficacy, Safety, and Biomarkers for Second-Line Axitinib in Patients with Advanced Hepatocellular Carcinoma: From a Randomized Phase II Study

“…Postprogression survival, defined as the time between the last day of treatment and death or last visit recorded, has been demonstrated to strongly correlate with median OS [11,12]. Additionally, if there are more patients in the placebo/BSC arm who are intolerant to sorafenib but receive sorafenib rechallenge post-study treatment, those patients may benefit from sorafenib rechallenge after failure of study treatment, as has been reported in another study [13].…”

Drug rechallenge and treatment beyond progression—implications for drug resistance

“…In another study of patients with metastatic RCC, stable disease was observed in six out of eight patients who originally discontinued sorafenib because of progressive disease and were then retreated with the same drug. 81 In these studies, antiangiogenic TKI rechallenge seems to have activity in RCC—and possibly in other malignancies, as observed in GIST case studies 82,83 —suggesting that resistance to sunitinib or sorafenib might be transient, at least in some individuals. 80 …”

The role of rechallenge with targeted therapies in metastatic renal-cell carcinoma

“…In a case series of 12 patients who had failed first-line sorafenib and subsequent anti-VEGF therapies or mTOR inhibitors, eight (67%) achieved stable disease upon sorafenib rechallenge, with median PFS of 5.4 months [32]. In contrast to sunitinib rechallenge, the duration of PFS with sorafenib rechallenge did not correlate with the PFS duration observed with initial sorafenib treatment or with the length of the interval between initial treatment and rechallenge.…”

“…A summary of studies evaluating rechallenge either with agents from the same class or the same agent are provided in Table 2 [16,[29][30][31][32][33][34][35]. The majority of studies exploring rechallenge with the same agent have focused on sunitinib, and have been summarized in a recent review by Porta et al [14 && ].…”