PracticeUpdate: Haematology & Oncology

ESMO 2016 29

Abstract 752P Radium-223 re-treatment from an international, prospective, open-label study in patients with castration- resistant prostate cancer and bone metastases. O Sartor, D Heinrich, N Mariados, et al • In this study, 44 patients with CRPC with bone metastases who progressed after initial radium-223 treatment received additional radium-223 injections. Of these patients, 29 received all six additional injections. After a median 6 months from last radium-223 injection, no significant differences in treatment-emergent adverse event incidence in the retreatment group versus the initial treatment group were noted. Only 3 patients in the retreatment group reported grade 3 or 4 treatment- related adverse events. After a maximum follow-up of 11.4 months, median time to PSA progression was 2 months. Median time to alkaline phosphatase progression was not reached after a follow-up of 12.8 months. • Retreatment with radium-223 was well-tolerated, with a toxicity profile similar to that observed in ALSYMPCA. Abstract 760P A post hoc analysis of radiographic progression with nonrising prostate-specific antigen in patients with metastatic castration-resistant prostate cancer (mCRPC) in the PREVAIL study. AH Bryce, JJ Alumkal, A Armstrong, et al • This post hoc analysis included 872 chemotherapy-naive men with mCRPC who had received enzalutamide to identify patients with rising PSA versus non-rising PSA at the time of radiographic progression. Non-rising PSA was identified in 19% of the 265 patients with radiographic progression and evaluable PSA levels. Patients with non- rising PSA exhibited significantly shorter median PFS compared with patients with rising PSA, although OS was similar. Soft-tissue disease developed in 40.3% of patients who had bone-only disease at baseline. • This study highlights the need to employ surveillance imaging in addition to PSA monitoring in patients with mCRPC, warranting further trials to evaluate the effect of non-rising PSA on OS. Abstract 761P How should we treat castration-resistant prostate cancer patients who have received androgen deprivation therapy (ADT) plus docetaxel upfront for hormone- sensitive disease? Mature analysis of the GETUG-AFU 15 phase III trial. P Lavaud, G Gravis, C Legoupil, et al • This retrospective study including patients with CRPC from the GETUG-AFU 15 phase 3 trial who received ADT or ADT plus docetaxel was conducted to investigate activity of treatments used beyond progression. Of the 245 men who received one or more treatments at progression, only 17% reported grade 3 or 4 events. Patients who received ADT only had a median overall survival of 2.29 years compared with 1.97 years in patients who received ADT plus docetaxel. Of patients receiving docetaxel- based chemotherapy as second-line treatment who in first-line received ADT plus docetaxel, fewer had a PSA response, more exhibited a symptomatic response, and overall survival was decreased compared with patients who received docetaxel-based chemotherapy as first-line treatment for CRPC. • This study demonstrated limited benefits of docetaxel rechallenge in these patients.

Cabozantinib has potential to become first-line treatment for renal cell carcinoma Cabozantinib improved progression-free survival and the response rate versus sunitinib significantly in a phase 2 multicentre trial in patients with metastatic renal cell carcinoma. T oni Choueiri, MD, of the Dana-Farber Cancer Institute, Boston, Massa- chusetts, explained, “Unlike sunitinib, which targets vascular endothelial growth factor receptors, cabozantinib targets tyrosine kinase enzymes. Cabozantinib also inhibits mesenchymal-epithelial transition (MET) factor and AXL kinase.” Dr Choueiri asserted, “Both MET and AXL seem to be associated with tumour progression. But more importantly, animal models showed that the development of resistance to vascular endothelial growth factor inhibitors like sunitinib can be mediated by AXL kinase and MET factor.” A total of 157 patients with untreated clear cell metastatic renal cell carci- noma of intermediate or poor risk were randomised to oral cabozantinib (60 mg once daily) or sunitinib (50 mg once daily). Patients who received cabozantinib exhibited a 31% reduction in the median rate of progression or death versus those treated with sunitinib (8.2 vs 5.6 months, P = 0.012). These patients also demonstrated a significantly higher objective response rate than patients who received sunitinib (46% vs 18%). Dr Choueiri and colleagues observed a similar rate of adverse events in the two groups (70.5% grade 3 or higher adverse events for cabozantinib vs 72.2% for sunitinib). The most common adverse events for both drugs included diarrhoea, fatigue, hypertension, palmar-plantar erythrodysesthesia, and haematological events. Sixteen patients in each group discontinued early due to adverse events. Good-risk patients were not included. No biological or clinical rationale would preclude cabozantinib in good-risk patients, however. Dr Choueiri concluded, “Cabozantinib is approved for second or later lines of therapies (in the US), after patients have progressed on a vascular endothelial growth factor/tyrosine kinase inhibitor, but this data shows that cabozantinib has the potential to become a first-line standard treatment.” Bernard Escudier, MD, of the Institut Gustave-Roussy, Paris, commented, “For many years, sunitinib has been the most commonly used first-line stand- ard of care for metastatic renal cell carcinoma. Recently, cabozantinib was proven to be active second line, especially after sunitinib failure.” He added that results of the study raise numerous questions. Among them: • Are the results expandable to all metastatic renal cell carcinoma patients, including the good prognosis group? • Should cabozantinib become a new, first-line standard of care? • How do we interpret the several ongoing phase 3 first-line trials in which sunitinib is the control arm? Dr Escudier concluded, “While more mature data and additional studies using cabozantinib in the first-line setting will be required, this study has raised expectations in the treatment of metastatic renal cell carcinoma.”

DECEMBER 2016