PracticeUpdate: Haematology & Oncology

ESMO 2016

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In patients age 70 years and older, capecitabine monotherapy at a starting dose of 2000 mg/m 2 or lower is associated with a median time to progression of 8.2 months and a clinical benefit rate of 43–67%. >8

Changing the sunitinib schedule from 4/2 to 2/1, rather than reducing the dose, was safe and resulted in a longer median progression-free and overall survival in patients with metastatic renal cell carcinoma. >9

The way we’re thinking about bladder cancer is definitely changing. In the past, all of our trials would exclude patients with a predominant nonurothelial component. >13

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, Massachusetts, explained, “Unlike sunitinib, which targets vascular endothe- 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 standard 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.”

lial growth factor receptors, cabozantinib targets tyrosine kinase enzymes. Cabozantinib also inhibits mesenchy- mal-epithelial transition (MET) factor andAXL kinase.” Dr Choueiri asserted, “BothMET andAXL seem to be associatedwith tumour progression. But more importantly, animal models showed that the development of resistance to vascular endothelial growth factor inhibitors like suni- tinib can be mediated by AXL kinase and MET factor.” A total of 157 patients with untreated clear cell metastatic renal cell carcinoma 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 signifi- cantly 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.

Palbociclib + letrozole maintains health-related quality of life vs letrozole alone in treatment-naive postmenopausal ER-positive, HER2-negative metastatic breast cancer The addition of palbociclib to

T his positive finding adds to the significant improvement in progression-free survival seen with palbociclib in PALOMA-2. Laura Esserman, MD, of the University of California, San Francisco, explained that palbociclib + letrozole significantly improved progression-free survival versus letrozole alone in the phase 3 PALOMA-2 trial. Quality of life is a critical consideration when adding tar- geted agents to hormone therapy in metastatic breast cancer. Dr Esserman and colleagues compared patient-reported health-related quality of life in treatment-naive postmenopausal patients with oestrogen receptor-positive, HER2-neg- ative metastatic breast cancer in PALOMA-2. PALOMA-2 randomised patients 2:1 to palbociclib + letrozole (n=444) or placebo + letrozole (n=222). Patient-reported outcomes were assessed at baseline, day 1 of cycles 2 and 3 and day 1 of every other cycle from cycle 5 until the end of treatment using the

Functional Assessment of Cancer Therapy – Breast (FACT-B) questionnaire. FACT- B includes FACT-General (FACT-G) and the breast cancer-specific subscale (BCS). FACT-B produces five subscale scores: 1. Physical well-being 2. Social/family well-being

between treatment groups in change from baseline scores for: • Physical well-being (–0.5 vs –0.3) • Social/family well-being (–0.6 vs –0.7)

letrozole maintains health-related quality of life in treatment-naive postmenopausal patients with oestrogen receptor-positive, HER2-negative metastatic breast cancer and showed no significant difference versus letrozole alone.

• Emotional well-being (0.7 vs 0.5) • Functional well-being (0.2 vs 0.3)

Overall change from baseline scores was comparable for the BCS (0.19 vs 0.83; P = 0.055), Trial Outcome Index (–0.1 vs 0.71; P = 0.325), FACT- G (–0.39 vs –0.53; P = 0.882), and FACT-B (–0.11 vs 0.22; P = 0.782) scores. Dr Esserman concluded that the addition of palbociclib to letrozole maintains health- related quality of life in treatment-naive postmenopausal patients with oestrogen receptor-positive HER2-negative metastatic breast cancer and showed no significant difference compared to letrozole alone. This data adds favourably to the significant improvement in progression-free survival seen in PALOMA-2.

3. Emotional well-being 4. Functional wellbeing 5. Breast Cancer Subscale (BCS).

The above are used to derive overall FACT- B, FACT-G, and Trial Outcome Index (TOI) scores. A higher score indicates a better qual- ity of life. Repeated measures mixed-effects analyses were performed to compare changes from baseline in each subscale and FACT-B scores, controlling for baseline. Baseline scores were comparable between the two treatment arms for FACT-B (102 vs 103), FACT- G, TOI, and each subscale score. No significant differences were observed

VOL. 1 • No. 5 • 2016