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Nivolumab-ipilimumab combination confers durable OS, PFS benefit in metastatic melanoma

BARCELONA, Spain — The combination of nivolumab and ipilimumab improved long-term survival compared with either of the immunotherapy drugs alone for patients with metastatic melanoma, according to a 5-year analysis of the randomized, phase 3 CheckMate 067 trial presented at European Society for Medical Oncology Congress.

“In the past, metastatic melanoma was regarded as untreatable,” James Larkin, MD, consultant medical oncologist at The Royal Marsden NHS Foundation Trust in London, said in a press release. “Oncologists considered melanoma different than other cancers — it couldn’t be treated once it had spread. Traditional chemotherapy never really worked well. This treatment transforms the disease to one with an approximately 50% cure rate. The priority now is to find ways to cure the remaining 50%.”

Results of CheckMate 067 have shown nivolumab (Opdivo, Bristol-Myers Squibb), in combination with ipilimumab (Yervoy, Bristol-Myers Squibb) and as monotherapy, significantly improved objective response, PFS and OS compared with ipilimumab alone among patients with advanced, previously untreated melanoma. The 5-year analysis represents the longest phase 3 follow-up of checkpoint inhibitor combination therapy.

Larkin and colleagues randomly assigned 945 patients with previously untreated, stage III or stage IV melanoma to nivolumab in combination with ipilimumab (n = 314), nivolumab with placebo (n = 316), or ipilimumab with placebo (n = 315).

The researchers stratified patients by PD-L1 status, BRAF mutation status and metastasis stage. Treatment was administered until disease progression or unacceptable toxicity.

PFS and OS served as the primary endpoints.

Minimum follow-up was 60 months.

Results showed median PFS of 11.5 months (95% CI, 8.7-19.3) for patients assigned the combination therapy, 6.9 months (95% CI, 5.1-10.2) for patients in the nivolumab group and 2.9 months (95% CI, 2.8-3.2) for patients in the ipilimumab group. Patients in the combination group also had a higher 5-year PFS rate (36%; 95% CI, 31-42) than patients assigned nivolumab alone (29%; 95% CI, 24-35) and ipilimumab alone (8%; 95% CI, 5-12).

Median OS was not reached (95% CI, 38.2-not reached) for patients in the combination group, compared with 36.9 months (95% CI, 28.2-58.7) for the nivolumab group and 19.9 months (95% CI, 16.8-24.6) for the ipilimumab group.

Researchers observed 5-year OS rates of 52% (95% CI, 46-57) for nivolumab plus ipilimumab, 44% (95% CI, 39-50) for nivolumab and 26% (95% CI, 22-31) for ipilimumab. Larkin noted the dramatic improvement compared with a decade ago — prior to the introduction of ipilimumab monotherapy — when 5-year survival for melanoma was about 5%.

Overall, 74% of patients assigned nivolumab plus ipilimumab, 58% of patients assigned nivolumab and 45% of patients assigned ipilimumab were alive and free from subsequent therapy at time of data cutoff. Researchers observed no sustained reduction in quality of life during or after treatment with nivolumab, either alone or with ipilimumab.

“We know that the two immunotherapy drugs together can have significant side effects and some patients even need to discontinue treatment,” Larkin said. “But for those patients who did stop treatment because of side effects, it did not impair the success of the therapy. “One of the key points about immunotherapies is that you can re-educate the immune system even with a short duration of treatment. This is in contrast to other treatments like chemotherapy, which require a full course to be effective.”– by John DeRosier

Reference:

Larkin JM, et al. Abstract 68_PR. Presented at: European Society for Medical Oncology; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

Disclosures: Bristol-Myers Squibb funded this study. Larkin reports honoraria from, consultant roles with and/or research grants from Achilles, AstraZeneca, Aveo, Boston Biomedical, Bristol-Myers Squibb, Covance, Eisai, EUSA Pharma, GlaxoSmithKline, Ipsen, Incyte, iOnctura, Kymab, Merck, Nektar, Novartis, Pierre Fabre, Pfizer, Roche and Secarna. Please see the abstract for all other authors’ relevant financial disclosures.

BARCELONA, Spain — The combination of nivolumab and ipilimumab improved long-term survival compared with either of the immunotherapy drugs alone for patients with metastatic melanoma, according to a 5-year analysis of the randomized, phase 3 CheckMate 067 trial presented at European Society for Medical Oncology Congress.

“In the past, metastatic melanoma was regarded as untreatable,” James Larkin, MD, consultant medical oncologist at The Royal Marsden NHS Foundation Trust in London, said in a press release. “Oncologists considered melanoma different than other cancers — it couldn’t be treated once it had spread. Traditional chemotherapy never really worked well. This treatment transforms the disease to one with an approximately 50% cure rate. The priority now is to find ways to cure the remaining 50%.”

Results of CheckMate 067 have shown nivolumab (Opdivo, Bristol-Myers Squibb), in combination with ipilimumab (Yervoy, Bristol-Myers Squibb) and as monotherapy, significantly improved objective response, PFS and OS compared with ipilimumab alone among patients with advanced, previously untreated melanoma. The 5-year analysis represents the longest phase 3 follow-up of checkpoint inhibitor combination therapy.

Larkin and colleagues randomly assigned 945 patients with previously untreated, stage III or stage IV melanoma to nivolumab in combination with ipilimumab (n = 314), nivolumab with placebo (n = 316), or ipilimumab with placebo (n = 315).

The researchers stratified patients by PD-L1 status, BRAF mutation status and metastasis stage. Treatment was administered until disease progression or unacceptable toxicity.

PFS and OS served as the primary endpoints.

Minimum follow-up was 60 months.

Results showed median PFS of 11.5 months (95% CI, 8.7-19.3) for patients assigned the combination therapy, 6.9 months (95% CI, 5.1-10.2) for patients in the nivolumab group and 2.9 months (95% CI, 2.8-3.2) for patients in the ipilimumab group. Patients in the combination group also had a higher 5-year PFS rate (36%; 95% CI, 31-42) than patients assigned nivolumab alone (29%; 95% CI, 24-35) and ipilimumab alone (8%; 95% CI, 5-12).

Median OS was not reached (95% CI, 38.2-not reached) for patients in the combination group, compared with 36.9 months (95% CI, 28.2-58.7) for the nivolumab group and 19.9 months (95% CI, 16.8-24.6) for the ipilimumab group.

Researchers observed 5-year OS rates of 52% (95% CI, 46-57) for nivolumab plus ipilimumab, 44% (95% CI, 39-50) for nivolumab and 26% (95% CI, 22-31) for ipilimumab. Larkin noted the dramatic improvement compared with a decade ago — prior to the introduction of ipilimumab monotherapy — when 5-year survival for melanoma was about 5%.

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Overall, 74% of patients assigned nivolumab plus ipilimumab, 58% of patients assigned nivolumab and 45% of patients assigned ipilimumab were alive and free from subsequent therapy at time of data cutoff. Researchers observed no sustained reduction in quality of life during or after treatment with nivolumab, either alone or with ipilimumab.

“We know that the two immunotherapy drugs together can have significant side effects and some patients even need to discontinue treatment,” Larkin said. “But for those patients who did stop treatment because of side effects, it did not impair the success of the therapy. “One of the key points about immunotherapies is that you can re-educate the immune system even with a short duration of treatment. This is in contrast to other treatments like chemotherapy, which require a full course to be effective.”– by John DeRosier

Reference:

Larkin JM, et al. Abstract 68_PR. Presented at: European Society for Medical Oncology; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

Disclosures: Bristol-Myers Squibb funded this study. Larkin reports honoraria from, consultant roles with and/or research grants from Achilles, AstraZeneca, Aveo, Boston Biomedical, Bristol-Myers Squibb, Covance, Eisai, EUSA Pharma, GlaxoSmithKline, Ipsen, Incyte, iOnctura, Kymab, Merck, Nektar, Novartis, Pierre Fabre, Pfizer, Roche and Secarna. Please see the abstract for all other authors’ relevant financial disclosures.

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