ESMO 2016. LBA14_PR. FALCON: A phase III randomised trial of fulvestrant 500 mg vs. anastrozole for hormone receptor-positive advanced breast cancer
M. J. Ellis et al.
Results: In total, 462 patients (fulvestrant, n = 230; anastrozole, n = 232) were randomised with both arms being well balanced. The trial met its’ primary endpoint and final results demonstrated a statistically significant improvement in PFS with fulvestrant vs. anastrozole (hazard ratio 0.797 [95% confidence interval 0.637, 0.999]; p = 0.0486; median PFS, 16.6 vs. 13.8 months, respectively). Subgroup analysis suggested an even greater advantage for fulvestrant in the patient subpopulation without visceral disease (22.3 vs. 13.8 months). OS maturity was 31% at a median follow-up of 25.0 months. Treatment impact on HRQoL was similar in both treatment groups. The most common adverse events were arthralgia (16.7% vs. 10.3%) and hot flushes (11.4% vs. 10.3%) for fulvestrant and anastrozole, respectively.
Conclusions: These results confirm the superior efficacy of fulvestrant over anastrozole in postmenopausal women with hormone receptor-positive locally advanced or metastatic breast cancer who have not received prior hormonal therapy.
CARE Faculty Perspective: Results from the phase III FALCON trial are consistent with the previously published data from the phase II FIRST trial and suggest that fulvestrant is an optimal first-line endocrine therapy for patients with no prior exposure to endocrine therapy. There remains some discussion and need for clarification around the observed versus planned statistically significant hazard ratio in FALCON, but, even with this caveat, the option of fulvestrant for the first-line therapy of endocrine-sensitive metastatic breast cancer warrants consideration, particularly with its’ very modest toxicity profile. The observations for the patient subset with non-visceral disease are of interest and suggests a particular subgroup potentially deriving preferential benefit.
ESMO 2016. Abstract 227PD. Everolimus use in breast cancer patients: A population-based study
M. Chavez-Macgregor et al.
Results: In all, 2949 everolimus-treated breast cancer patients were identified through administrative databases with a median age of 60. The median cumulative day supply of everolimus was 112 days. At the time of first claim the prescribed dose was 10mg in 76.9% with 2.7% receiving a 7.5mg; 7.8% a 5mg and 2.6% a 2.5mg prescription. 77.3% of patients maintained the starting dose, with 16.7% having a dose reduction and 6% a dose escalation. A total of 1488 patients (50.5%) had claims associated with known everolimus-related toxicities; nausea, vomiting and electrolyte imbalances were identified in 31.7% of the patients, 17.9% had metabolic toxicities, 11.9% hematological toxicities, 5.1% stomatitis, 4.7% rash and 0.4% had a claim for pneumonitis. A total of 644 patients (21.8%) were hospitalized or had an ER visit associated with the toxicities above.
Conclusions: Half of the patients receiving everolimus had a claim for a known everolimus-related toxicity and 21.8% were hospitalized or visited the ER while on everolimus for toxicity. We cannot rule out the possibility that symptoms that lead to the hospitalizations/ER visit were related to the breast cancer or to other causes, but this data provides real world information of the toxicities associated with everolimus treatment. The pattern of toxicities differs from what has been reported in clinical trials, and it is possible that only serious toxicities are associated with a claim.
CARE Faculty Perspective: This was a large study of 2949 patients that gives insight into the real-world toxicities associated with everolimus. Over 20% of treated patients visited an ER or were hospitalized while on everolimus which emphasizes the importance of proactively managing toxicities with both medical prophylaxis (e.g. dexamethasone oral rinse as in the SWISH study Rugo H et al ASCO 2016) and excellent patient communication and education.