Immunotherapy substantially improves survival in metastatic melanoma, from 5-year survival levels of 5% a decade ago, to 52% now, a clinical trial shows. Doctors said it was an extraordinary and rapid transformation in care.
“In the past, metastatic melanoma was regarded as untreatable,” said Professor James Larkin, a consultant at the Royal Marsden NHS Foundation Trust. He is quoted in a BBC report as saying: “Oncologists considered melanoma different to other cancers, it couldn’t be treated once it had spread.” People tended to live between six and nine months after diagnosis.
The trial investigated two immunotherapy drugs which are designed to enhance the immune system and let it attack cancer. There were 945 patients in the trial, a third were given nivolumab, a third were given ipilimumab and a third were given both. Doctors then looked at the five-year survival rate – the proportion of patients still alive after five years.
The report says results showed: 26% were still alive on ipilimumab alone; 44% were still alive on nivolumab alone; and 52% were still alive when given both.
“It’s been an amazing surprise to see so much progress in such a short a period of time,” Larkin is quoted in the report as saying. He said: “It’s been the most extraordinary transformation from a disease that was regarded, among all the cancers as the most difficult to treat, the most serious prognosis.
He said there is now “the possibility that 50% of people with stage four melanoma are alive five years after having immunotherapy treatment.”
Background: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.
Methods: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.
Results: At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.
Conclusions: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab.
James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez, Jean-Jacques Grob, Piotr Rutkowski, Christopher D Lao, C Lance Cowey, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Pier F Ferrucci, Michael Smylie, David Hogg, Andrew Hill,Ivan Márquez-Rodas, John Haanen, Massimo Guidoboni, Michele Maio, Patrick Schöffski, Matteo S Carlino, Céleste Lebbé, Grant McArthur,Paolo A Ascierto, Gregory A Daniels, Georgina V Long, Lars Bastholt, Jasmine I Rizzo, Agnes Balogh, Andriy Moshyk, F Stephen Hodi, Jedd D Wolchok