One of two patients with metastatic melanoma lives after 5 years

BARCELONA, Spain – One of two patients with metastatic melanoma treated with the combination of ipilimumab ( Yervoy Bristol-Myers Squibb) and nivolumab ( Opdivo Bristol-Myers Squibb) is still in live after 5 years, showing updated results from the longest-running double immunotherapy trial.

"This is a great improvement on what we have seen historically," said principal investigator James Larkin, FRCP, PhD, of the Royal Marsden NHS Foundation Trust, London, United Kingdom.

"Ten years ago, 5-year survival for melanoma was around 5%. With ipilimumab monotherapy, which has been used for about 10 years, about 20% of patients are long-term survivors and the rest live only 6 to 9 months," he added.

Larkin presented the new survival data, which comes from the CheckMate 067 trial, here at the European Society for Medical Oncology Annual Meeting, and the results were also published simultaneously in the New England Journal of Medicine .

Melanoma expert Michael Postow, MD, at Memorial Sloan Kettering Cancer Center in New York City, agreed that this data makes history.

"This study provides the longest follow-up information we have for patients treated with nivolumab and the ipilimumab combination. It is notable that over 50% of patients with advanced melanoma now have long-term survival," he told Medscape Medical News .

He added that the combination has an established place in clinical practice for not only melanoma patients, but also for patients with renal cell carcinoma and certain types of colon cancer.

Change in the treatment landscape of advanced melanoma

Postow explained that the advent of ipilimumab introduced the field of oncology to the incredible possibilities of immune Nivolumab and pembrolizumab then showed that the results could be even better ̵[ads1]1; and with fewer side effects – than with ipilimumab.

"Now the combination of nivolumab and ipilimumab has begun a new era of combination immunotherapy, further increasing beneficial results, he said, adding that the combination is" a fantastic step forward "for patients with melanoma and other cancers.

" We now need to find ways to identify which patients benefit most, and if new ways to deliver nivolumab and ipilimumab preserve antitumor efficacy with fewer side effects, "Postow explained.

" The combination is not for all patients with melanoma, as patients must be chosen properly given the potential for side effects, "Postow said. But he added that the combination of nivolumab and ipilimumab is more powerful than nivolumab or pembrolizumab ( Keytruda Merck) alone, with higher response rates and more side effects.

"If patients are appropriate for both nivolumab and ipilimumab combinations, and for either nivolumab or pembrolizumab alone, both should be Gives are discussed with patients and the decision between them weighed carefully, "he said.

Larkin agreed, noting that there is currently no method for predicting which patients are most likely to benefit from combination immunotherapy. "Deciding what treatments to give is a matter for doctors to discuss with individual patients and their families," he said.

"The two drugs together definitely have a role in the treatment of metastatic melanoma and will be the choice for some patients. For others, the decision may be to give the drugs in order," Larkin said.

CheckMate 067 Results

CheckMate 067 randomly assigned 945 patients to receive the combination of ipilimumab and nivolumab (n = 314), nivolumab (n = 316), or ipilimumab (n = 315).

The 5-year overall survival rates were 52% for the combination of nivolumab and ipilimumab, 44% for nivolumab and 26% for ipilimumab.

Progression-free survival after 5 years mirrored OS data: 36% for the combination, 29% for nivolumab alone and 8% for ipilimumab alone.

Larkin reported that objective response rate (ORR) was seen in 58% of patients receiving the combination 45% of patients receiving nivolumab alone and 19% receiving ipilimumab alone. "While ORR has remained stable, the number of complete responses has improved over the course of 3-year, 4-year and 5-year analysis," he said.

Fewer patients on the combination received subsequent therapies (46% for the combination 59% for nivolumab alone and 75% for ipilimumab alone.

"The treatment-free interval (TFI) is an important outcome for patients," Larkin said. who discontinued treatment, TFI was longest for patients receiving the combination (18.1 months compared to 1.9 months for nivolumab alone and 1.8 months for ipilimumab alone).

Three-quarters of patients (74%) receiving the combination was alive and treatment-free at the end of 5 years, significantly higher than 58% of patients receiving nivolumab alone and 45% of patients receiving ipilimumab alone.

No new safety signals or treatment-related deaths were reported after 5 years, Larkin reported. [19659016] Activity Against Brain Metastases

Postow commented that the combination of nivolumab and ipilimumab is the preferred go-to therapy for many patients with advanced melanoma, especially in particular patients with brain metastases.

On this topic, Georgina V. Long, MD, of the Melanoma Institute Australia in Sydney, reported in another presentation that patients receiving this combination had the best intracranial response (51% for the combination and 20% for nivolumab alone) and also better survival rates.

Long's data came from an independent, investigative-driven ABC (Anti-PD-1 Brain Collaboration) study, which compared the combination of ipilimumab and nivolumab with nivolumab alone in patients with brain metastases (abstract 1311O).

The ABC trials from Australia and New Zealand registered 60 patients who received no treatment for asymptomatic brain metastases to receive the combination ipilimumab and nivolumab (n = 35) or nivolumab alone (n = 25).

The study also included a separate cohort of 18 patients who were previously treated or had symptomatic brain metastases. These patients received nivolumab alone, and these results will not be discussed further.

The rates of complete (CR) and partial (PR) responses were also higher for patients receiving the combination. CR and PR were 26% and 26%, respectively, for patients receiving the combination compared to 16% and 4%, respectively, for patients receiving nivolumab.

Best extracranial responses were also higher for patients receiving the combination (57% vs 29% for nivolumab alone.

Three-year intracranial PFS was 43% for combination patients and 15% for nivolumab patients alone. Three-year operating system was 49 % for patients receiving the combination and 42% for patients receiving nivolumab alone.

Long reported that there were no unexpected toxicities and that quality of life was maintained across study groups.

Larkin reports receiving consultancy fees, honoraria and / or research grants from Achilles Therapeutics, AstraZeneca, Boston Biomedicals, Bristol-Myers Squibb, Eisai, EUSA Pharma, Imugen, IOnctura, Ipsen, Kymab, Merck Serono, MSD, Nectar, Novartis, Pierre Fabre, Pfizer, Roche / Genentech, Secarna and Vitaccess Long reported on consulting with Aduro, Amgen, Array, Bristol-Meyers Squibb, Merck MSD, Novartis, Roche and Pierre Fabre Postow receives institutional support from BMS, Merck, RGenix, Infinity, AstraZeneca, Novartis and Array BioPharma . He also receives consultancy fees / fees from BMS, Merck, Array BioPharma, Novartis, Aduro, Incyte and NewLink Genetics .

European Society for Medical Oncology (ESMO) Annual Meeting 2019: Abstract LBA 68_PR (CheckMate 067), Abstract 1311O. Presented September 28, 2019.

New England Journal of Medicine . Published online September 28, 2019. Summary

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