Adjuvant monotherapy with nivolumab provides better outcomes than combining it with ipilimumab in high-risk melanoma

• This is shown in the results of the CheckMate 915 study, in which Dr. Eva Muñoz-Couselo, investigator in the Breast Cancer and Melanoma Group at the Vall d’Hebron Institute of Oncology (VHIO) and medical oncologist at the Vall d’Hebron Hospital, both of which are part of the Vall d’Hebron Campus, took part.

• The positive results from using this combination in treating metastatic melanoma were a source of optimism regarding its usefulness in adjuvant therapy, an option that has finally been ruled out.

• The results of the study have just been published in the Journal of Clinical Oncology, showing that the same combination does not behave in the same way in adjuvant therapy as in treatment for metastasis, at least in melanoma.

Combining different treatments in cancer is not new. Making use of synergies between different drugs aims to enhance their effects and improve patient outcomes. However, such combinations are not always effective, as shown by the results of the CheckMate 915 study, in which the use of nivolumab as monotherapy in adjuvant therapy for stage IIIA-D or stage IV resected high-risk melanoma was as effective as combining it with ipilimumab, but with much lower toxicity.

“In the context of treatment for metastatic disease, we have seen that this drug combination achieved a much higher median survival than from treatment with ant-PD1 alone. This led to the idea of seeing whether the combination was also effective in preventing recurrence in the context of adjuvant therapy,” explains Dr. Eva Munoz-Couselo, researcher in the Breast Cancer and Melanoma Group of the Vall d’Hebron Institute of Oncology (VHIO) and Medical Oncologist at the Vall d’Hebron Hospital, one of the authors of the article now published in the Journal of Clinical Oncology that provides data from the CheckMate 915 study.¹

The combination does not improve efficacy and has greater toxicity

The CheckMate 915 trial enrolled a total of 1,833 patients with stage IIIB-D and stage IV resected melanoma, who were divided into two groups. One received monotherapy with nivolumab, an anti-PD-1 monoclonal antibody, while the other received the combination of nivolumab with ipilimumab, an anti-CTLA-4 antibody. Both drugs had proved useful in the treatment of advanced melanoma, and the results of the CheckMate 067 study, presented in ASCO in 2021, showed that their combination significantly increased patient survival.²

The aim of this new trial was to see whether the use of this combination would be successful in increasing recurrence-free survival time in the context of adjuvant therapy. However, the results showed that there was no significant difference between the groups, with about 64% of patients free of recurrence after 24 months of treatment. “In contrast, we also saw that there was greater toxicity in the patients who received the combined treatment, with up to 32.6% reporting significant adverse effects, compared with only 12.8% of those receiving nivolumab monotherapy,” explains Dr. Eva Munoz-Couselo.

Based on these data, the study authors concluded that nivolumab monotherapy treatment is currently the best possible option, following surgery, in patients with high-risk melanoma, establishing how important it is to stress the difference between adjuvance and treatment of metastatic disease, at least for melanoma. “It is also important to prioritise clearly an effective, low-toxicity treatment such as nivolumab in this adjuvant therapy, demonstrating that the definitive standard of treatment must be with a single anti-PD-1 drug,” adds the VHIO researcher.

References:

1. Weber JS, Schadendorf D, Del Vecchio M, Larkin J, Atkinson V, Schenker M, Pigozzo J, Gogas H, Dalle S, Meyer N, Ascierto PA, Sandhu S, Eigentler T, Gutzmer R, Hassel JC, Robert C, Carlino MS, Di Giacomo AM, Butler MO, Muñoz-Couselo E, Brown MP, Rutkowski P, Haydon A, Grob JJ, Schachter J, Queirolo P, de la Cruz-Merino L, van der Westhuizen A, Menzies AM, Re S, Bas T, de Pril V, Braverman J, Tenney DJ, Tang H, Long GV. Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915). J Clin Oncol. 2022 Sep 26:JCO2200533. doi: 10.1200/JCO.22.00533. Epub ahead of print. PMID: 36162037.
2. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Butler MO, Hill A, Márquez-Rodas I, Haanen JBAG, Guidoboni M, Maio M, Schöffski P, Carlino MS, Lebbé C, McArthur G, Ascierto PA, Daniels GA, Long GV, Bas T, Ritchings C, Larkin J, Hodi FS. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J Clin Oncol. 2022 Jan 10;40(2):127-137. doi: 10.1200/JCO.21.02229. Epub 2021 Nov 24. PMID: 34818112; PMCID: PMC8718224.