Nivolumab/ipilimumab demonstrates efficacy in patients with melanoma and brain metastases, according to results of the primary analysis of the phase 3 NIBIT-M2 trial, presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.
"Brain metastases represent a high unmet medical need, in which the therapeutic potential of immune-checkpoint(s) is being actively investigated," note the investigators in their presentation abstract, led by Anna Di Giacomo, MD, Associate Director of the Center for Immuno-Oncology at the University Hospital of Siena, Italy. "Temozolomide and fotemustine have been the therapeutic mainstay of melanoma patients with brain metastases for over two decades."
Results of phase 1 and 2 trials of nivolumab/ipilimumab have shown efficacy in patients with melanoma and asymptomatic brain metastases. The multicenter, open-label NIBIT-M2 trial is the first phase 3 trial investigating this combination in this population. Patients with melanoma and active, untreated and asymptomatic brain metastases were randomized to receive fotemustine, fotemustine/ipilimumab, or nivolumab/ipilimumab. The trial's primary end point was overall survival, with secondary end points that included intracranial objective response rate, intracranial disease control rate, and progression-free survival.
Of 80 patients who were randomized, 76 were treated. With a median follow-up of 39 months, nivolumab/ipilimumab resulted in a median overall survival of 29.2 months, compared with 8.5 months for fotemustine and 8.2 months for fotemustine/ipilimumab. Nivolumab/ipilimumab produced an intracranial objective response rate of 55.6%, compared with 26.1% for fotemustine and 34.6% for fotemustine/ipilimumab. Nivolumab/ipilimumab also resulted in the longest median progression-free survival (8.4 months, compared with 3.0 months for fotemustine and 3.3 months for fotemustine/ipilimumab).
"Unlike ipilimumab plus fotemustine, ipilimumab plus nivolumab significantly (P=0.009) improves the long-term survival of melanoma patients with brain metastases compared to fotemustine," conclude Dr. Di Giacomo and colleagues. "Ipilimumab plus nivolumab should represent the treatment of choice in first-line melanoma patients with brain metastases."
For More Information
Di Giacomo AM, Chiarion Sileni V, Del Vecchio M, et al (2020). Efficacy of ipilimumab plus nivolumab or ipilimumab plus fotemustine vs fotemustine in patients with melanoma metastatic to the brain: primary analysis of the phase III NIBIT-M2 trial. Ann Oncol (ESMO Virtual Congress Abstracts), 31(suppl_4):S672-S710. Abstract 1081MO. DOI:10.1016/annonc/annonc280
Image credit: Julio C. Valencia. Courtesy of the National Cancer Institute Center for Cancer Research