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Clinical practice shows significant differences in treatment outcomes across patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC). It is not known whether cabozantinib-induced adverse events are predictive factors of survival as in case of drugs such as sunitinib or axitinib. The study participants were 30 adult patients with mRCC treated with cabozantinib as a second- or further line setting. All adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Progression-free survival (PFS) values were calculated by taking the beginning of cabozantinib treatment as the start date and either disease progression or death as the end date. PFS were estimated using the Kaplan–Meier method, and compared using the log-rank test. We identified independent PFS predictors using multiple Cox proportional hazards models and reported hazard ratios (HR) with 95% confidence intervals. The median observation time cabozantinib treatment was 7.5 months, with a range of 2–15 months. During that time, 11 (37%) of the patients had mRCC progression. Median PFS on cabozantinib was not reached, and lower quartile was 6 months. All patients developed at least one adverse event in the course of cabozantinib therapy. Hypertension, hypothyroidism and HFS were observed most frequently, in about two-thirds of the patients. The co-incidence of multiple adverse events was common. Hypertension, hypothyroidism, diarrhea and liver toxicity were significantly associated with longer PFS values. Patients with three or more side effects had significantly longer PFS than those with two or fewer. Even though this study was conducted in a small patient sample and the observation time was relatively short our results confirm the predictive value of the incidence of adverse events during cabozantinib treatment in mRCC patients. To the best of our knowledge, this is the first study of this kind conducted in this group of patients.

Aims and background Clinical practice shows significant differences in treatment outcomes and toxicity of sunitinib across patients. This retrospective study assessed early predictive markers for progression-free survival (PFS) in patients with metastatic clear cell renal cell carcinoma (RCC) treated with sunitinib in the first-line setting. Methods We evaluated 28 patients with stage IV clear cell RCC (with good or intermediate MSKCC risk prognosis) treated at the Department of Oncology, University Hospital, Cracow between 2008 and 2013. Data included demographic profiles, adverse events during first cycle of therapy, treatment delays, and treatment outcomes. Sunitinib was administered on a standard schedule (50 mg/day, 4 weeks on, 2 weeks off). PFS values were estimated with the Kaplan-Meier method and compared using the log-rank test; we identified independent PFS predictors using multiple Cox regression models. Results PFS was significantly longer in patients who experienced at least 1 adverse event after the first cycle of sunitinib (median 17.6 months vs. 5.6; p = 0.006). Hypertension and hand-foot syndrome were significantly correlated with longer PFS (29.3 vs. 6.0 months; p = 0.002, and not reached vs. 9.8 months; p = 0.002, respectively). We observed a similar (though not significant) tendency for neutropenia (17.5 vs. 8.4 months; p = 0.055). In multiple Cox regression, hypertension was the only individual independent predictor of PFS, but the co-occurrence of any 2 or 3 sunitinib-induced adverse events also predicted longer survival. Conclusions Although small, our study suggests that hypertension and hand-foot syndrome predict longer PFS in patients with clear cell RCC treated with sunitinib. The co-occurrence of 2 or more side effects seems also a significant predictor of longer survival. Larger studies are warranted to confirm the correlation between co-occurring side effects and PFS.

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in ‘low’ and ‘intermediate’ Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p