There is good news for patients with melanoma who received immunotherapy. Survival results from a major clinical trial, CheckMate-067, show a sustained benefit after ten years.

CheckMate-067 is a trial testing the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) against each drug alone for 945 patients with advanced (Stage IV) melanoma. Survival outcome data was reported after ten years of patient follow-up, which is the longest period of follow up recorded for any PD-1 immunotherapy drug.¹

Nivolumab targets PD-1, which is the abbreviation for the T-cell programmed death-1 checkpoint protein. It is a human antibody and immune checkpoint inhibitor that reverses the immune system shutdown switch that cancer cells use to evade the immune system. Ipilimumab is an immunotherapy drug that targets the cytotoxic T-lymphocyte antigen 4 protein (CTLA-4), which blocks another shut-off switch used to evade the immune system.

After ten years, the overall survival rate for the combination of nivolumab plus ipilimumab was 43%. This was higher than nivolumab alone (37%) and ipilimumab alone (19%) after ten years.¹

The number of patients surviving with the combination of nivolumab plus ipilimumab was 92 out of 314 after ten years. This was higher than nivolumab alone (77 out of 316) and ipilimumab alone (35 out of 315). The median overall survival was 71.9 months with nivolumab plus ipilimumab, better than nivolumab (36.9 months), or ipilimumab (19.9 months).²

These results are excellent news considering that prior to 2011, when ipilimumab was approved for use in melanoma, no successful approach to treating advanced melanoma existed. Although chemotherapy has existed for many decades, it has generally not been successful treating melanoma. Prior to 2011, patients with advanced melanoma could expect a median overall survival of less than 12 months. In 2010 or earlier, they would likely have been enrolled in a clinical trial due to a lack of efficacious approaches. However, things started to change after research observations that the human immune system eventually ignores cancer in the body.

In the clinical trial, all groups receiving treatment had a low number of treatment-related side effects that suddenly emerged late in the clinical trial. No new safety signals or treatment-related deaths were observed since the analysis at three years. This suggests that patients are unlikely manifest new complications from treatment after 100 days, per the study.¹

The results of CheckMate-067 were presented on September 15, 2024, at ESMO in Barcelona. ESMO is the common term for the professional organization called the European Society for Medical Oncology. This group comprises over 35,000 members from oncology and related fields within 172 countries. The vision of ESMO includes serving “those engaged in action against cancer on a global level” and a commitment “to caring for the carers who lead the effort in their communities.” ³

ESMO hosts multiple small meetings throughout the year that are specific to oncology and gathers relevant professionals to discuss clinical research. ESMO also hosts an annual meeting, ESMO Congress, that brings together many professionals that encompass those who care for patients with all types of cancer.

This clinical trial follows initial results from this combination from 10 years ago. In 2013, successful results were shown from an early clinical trial with the combination of ipilimumab with nivolumab. The clinical activity showed melanoma tumors shrinking by 100% in the majority of patients, but not everyone who received concurrent ipilimumab and nivolumab.⁴

Overall, the results show a long-term benefit from combination immunotherapy.

 

References:

1. Larkin J, Chiarion-Sileni V, Gaudy-Marqueste C et al. 10-year survival outcomes from the phase 3 CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma. ESMO Congress 2024. Oral presentation LBA43 presented on September 15, 2024.
2. Wolchok JD, Chiarion-Sileni V, Rutkowski P et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2024.
3. The European Society for Medical Oncology. Accessed August 28, 2024 at https://www.esmo.org/.
4. Wolchok JD, Kluger H, Callahan MK et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122-33. doi: 10.1056/NEJMoa1302369.