Nivolumab and Ipilimumab combo bests monotherapy in improving clinical outcomes in Advanced Melanoma

In a new study CheckMate 067, the results demonstrated durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma.

This study was conducted by Jedd D. Wolchok and team, results of which were published in the Journal of Clinical Oncology on 24th November, 2021.

The progress of immune checkpoint inhibitors and BRAF- and MEK-targeted therapies has resulted in a significant improvement in the survival outcomes of patients with advanced melanoma. As a result, the objectives addressed in this study are After a 5-year follow-up, long-term survival of patients with advanced melanoma treated with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab was demonstrated in the phase III CheckMate 067 trial. The extent to which this benefit will last is of interest. We present CheckMate 067 6.5-year results, including the first report of melanoma-specific survival.

In the following study patients with previously untreated unresectable stage III or IV melanoma were assigned 1:1:1 randomly to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses), followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 Progression-free survival and overall survival (OS) with nivolumab + ipilimumab or nivolumab vs ipilimumab were coprimary end goals. Secondary end goals were objective response rate, effectiveness evaluations of nivolumab with ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis) was also assessed, which removes deaths unrelated to melanoma.

The results of this study stated as follow:

1. The median OS (minimum follow-up, 6.5 years) in the combination, nivolumab, and ipilimumab groups was 72.1, 36.9, and 19.9 months, respectively.

2. The median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates in patients with BRAF-mutant tumours were 57%, 43%, and 25%, respectively, and 46%, 42%, and 22% in those with BRAF–wild-type cancers.

3. The median treatment-free period in patients who quit therapy was 27.6, 2.3, and 1.9 months, respectively. There have been no new safety signals identified since the 5-year study.

In conclusion, the 6.5-year findings acquired in CheckMate 067 with the combination of first-line nivolumab + ipilimumab in patients with advanced melanoma include the longest median OS reported in a phase III melanoma research to date, as well as a median MSS that had not been achieved at 77 months.

Reference:

Wolchok, J. D., Chiarion-Sileni, V., Gonzalez, R., Grob, J.-J., Rutkowski, P., Lao, C. D., Cowey, C. L., Schadendorf, D., Wagstaff, J., Dummer, R., Ferrucci, P. F., Smylie, M., Butler, M. O., Hill, A., Márquez-Rodas, I., Haanen, J. B. A. G., Guidoboni, M., Maio, M., Schöffski, P., … Hodi, F. S. (2021). Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. In Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.21.02229