by Sylvie Lapostolle at ESMO
MADRID, Sep 12 (APM) - The three-year survival rate with the combination of Bristol-Myers Squibb's two immunotherapies Opdivo (nivolumab) and Yervoy (ipilimumab) in the first-line treatment of advanced melanoma has reached 58%, according to data presented at the meeting of the European Society for Medical Oncology (ESMO) in Madrid and published in the New England Journal of Medicine (NEJM).
The BMS CheckMate-067 trial showed that the combination of anti-PD-1 nivolumab and anti-CTLA-4 ipilimumab, two checkpoint inhibitors, extends progression-free survival (PFS), allowing the immunotherapy combination to be registered in this indication, with subsequent data on overall survival (OS) in January.
On Monday, Dr Jedd Wolchok of the Memorial Sloan-Kettering Cancer Center, New York, presented the survival data at three years for the Phase III trial that enrolled 945 patients who had not yet received treatment for their advanced melanoma.
With minimum follow-up of 36 months, median OS has still not yet been reached with nivolumab+ipilimumab but has been reached for the nivolumab alone arm, at 37.6 months versus 19.9 months in the ipilimumab alone arm.
Risk of death was cut by 45% with the combination compared to ipilimumab and by 35% with nivolumab compared to ipilimumab. Between the combination and nivolumab, risk of death was cut by 15%, but this is merely descriptive data as the trial was not designed to compare the combination with nivolumab.
The three-year survival rate reached 58% for the combination and 52% with nivolumab, versus 34% with ipilimumab.
Grade 3 or 4 adverse events occurred in 59% of patients receiving the combination, 21% of patients on nivolumab and 28% of those on ipilimumab.
As already reported, two deaths linked to the treatment occurred within 100 days of the last dose received: one death from neutropaenia in the nivolumab arm and one death from colitis with perforation in the ipilimumab arm. Two deaths not previously reported are described: a man aged 72 with a history of cardiac problems died of heart failure and auto-immune myocarditis on the 589th day (433 days after the last dose) and two months after having received nivolumab outside the trial context, and a woman aged 69 died on the 735th day (234 days after the last dose) of liver necrosis following elevation of liver enzymes.
OS is longer with the combination, or with nivolumab in comparison with ipilimumab, Wolchok said.
This benefit was noted in various subgroups. In patients with BRAF-mutated melanoma (who can also be given targeted therapies in first line, BRAF and MEK inhibitors), the three-year survival rate with the immunotherapies in combination even reached 68%, and 56% with nivolumab.
In these BRAF-mutated patients, median OS was reached: 39.1 months with the combination, 35.8 months with nivolumab and 18.5 months with ipilimumab.
In the KEYNOTE-006 trial, the other anti-PD-1, Merck & Co's Keytruda (pembrolizumab), was associated with median OS of 32.3 months and with a three-year survival rate of 50% (compared with 39% for ipilimumab), the authors said in the NEJM article, for comparison purposes.
(NEJM, online publication of September 11)