melanoma

Adjuvant Therapy with Nivolumab Combined with Ipilimumab versus Nivolumab Alone in Patients with Resected Stage IIIB-D/IV Melanoma (Results from the Checkmate 915 Trial)

Adjuvant Therapy with Nivolumab Combined with Ipilimumab versus Nivolumab Alone in Patients with Resected Stage IIIB-D/IV Melanoma (Results from the Checkmate 915 Trial)

On April 10, 2021, investigators reported on the results of the CheckMate 915 trial in adjuvant melanoma, comparing combination ipilimumab and nivolumab versus single agent nivolumab in patients with resected Stage IIIB-D/IV melanoma.

Background and Purpose

While the combination of nivolumab and ipilimumab has shown a statistically significant improvement in survival in patients with metastatic melanoma, with single agent nivolumab as well as ipilimumab having shown significant benefit in the adjuvant setting, the combination of ipilimumab and nivolumab is now reported on in a randomized clinical trial in patients with advanced stage IIIB-D/IV melanoma

Methods:

Patients with completely resected melanoma, were stratified by tumor PD-L1 expression and staging.  They were treated with nivolumab 240 mg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks or placebo controlled nivolumab 480 mg every 4 weeks alone for up to 1 year.  Dual endpoints for recurrence free survival in those with PD-L1 less than 1% and the intent to treat populations.  Distant metastasis free survival in patients with stage III disease was an exploratory endpoint.

Results

920 patients are randomized to the combination arm while 924 patients were randomized to the nivolumab monotherapy arm.  31 patient had stage IIIb disease in both arms.  53% and 52% had stage IIIC disease in each arm, respectively.  Complete lymph node dissection was performed in 64% in both arms.  Patients treated in the combination arm versus the single agent arm, have shorter median duration of therapy, 7.6 versus 11 months.  This translated into a lower overall nivolumab exposure, 3,840 versus 6,240 mg.  After minimal follow-up of 24 months, relapse free survival and DMFS were not different between treatment groups.  Grade 3 and 4 treatment-related adverse events were seen in 33% of patients treated with nivolumab plus ipilimumab at 13% with nivolumab monotherapy.  Discontinuation was seen in 32%, versus 10%, respectively. 4 treatment related deaths were seen in the combination arm.  In the intent to treat population, the combination therapy, 24-month relapse free survival rates were 64.6% versus 63.2%.  The number of events were 327 versus 347, respectively, hence the median was not reached.  The hazard ratio was 0.92, 97.295% confidence interval, 0.77–1.09, p=0.269.

Conclusion

The authors concluded “The NIVO + IPI1 regimen did not result in RFS or DMFS improvement vs NIVO in stage IIIB–D/IV resectable melanoma; safety profiles were consistent with previous studies. NIVO 480 mg Q4W outcomes in CheckMate 915 were similar to previous NIVO results and reinforce NIVO as an adjuvant standard of care in a study population that included pts with and without complete lymphadenectomy.”

Reference:

https://www.abstractsonline.com/pp8/#!/9325/presentation/5135

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