New six-and-a-half-year data from CheckMate -067, a randomized, double-blind, phase 3 clinical trial, demonstrating durable improvement in survival with first-line Nivolumab ( Opdivo ) plus Ipilimumab ( Yervoy ) therapy and Nivolumab monotherapy, versus Ipilimumab alone, in patients with advanced melanoma.
With a minimum follow-up of 6.5 years, median overall survival ( OS ) was 72.1 months with Nivolumab plus Ipilimumab ( 95% CI: 38.2-NR ), 36.9 months with Nivolumab ( 95% CI: 28.2-58.7 ) and 19.9 months with the Ipilimumab group ( 95% CI: 16.8-24.6 ).
In addition, the Nivolumab plus Ipilimumab combination has demonstrated a 6.5-year progression-free survival ( PFS ) rate of 34% ( median of 11.5 months ) while PFS rates were 29% ( median of 6.9 months ) and 7% ( median of 2.9 months ) for Nivolumab alone and Ipilimumab alone, respectively.
Of the 49% of patients alive and in follow-up, 77% of patients who received the combination ( 112/145 ), 69% of Nivolumab-treated patients ( 84/122 ) and 43% ( 27/63 ) of Ipilimumab-treated patients have been off treatment and never received subsequent systemic therapy.
Durable, sustained clinical benefit was also observed with Nivolumab plus Ipilimumab or Nivolumab alone across relevant subgroups, including in patients with BRAF mutation, wild-type tumors, and baseline liver metastases.
Among patients with BRAF-mutant tumors, the rate of overall survival at 6.5 years was 57% in patients who received Nivolumab plus Ipilimumab, 43% for Nivolumab alone, and 25% for Ipilimumab alone.
In patients with BRAF wild-type tumors, the rate of overall surival was 46% in patients who received Nivolumab plus Ipilimumab, 42% for Nivolumab alone and 22% for Ipilimumab alone.
The rate of overall survival among patients with liver metastases was 38% for those who received Nivolumab plus Ipilimumab, 31% for Nivolumab alone, and 22% for Ipilimumab alone.
Median duration of response ( DoR ) was not reached for those who received Nivolumab plus Ipilimumab nor Nivolumab,while the DoR for Ipilimumab-treated patients was 19.2 months.
The safety profile for Nivolumab plus Ipilimumab was consistent with prior findings, with no new safety signals observed and no additional treatment-related deaths occurring since the five-year analysis.
Grade 3/4 treatment-related adverse events were reported in 59% of patients in the combination group, 24% of patients in the Nivolumab group, and 28% of patients in the Ipilimumab group.
945 patients with previously untreated advanced melanoma were enrolled in CheckMate -067.
Patients in the combination group ( n=314 ) received Nivolumab 1 mg/kg plus Ipilimumab 3 mg/kg every three weeks ( Q3W ) for four doses followed by Nivolumab 3 mg/kg every two weeks ( Q2W ).
Patients in the Nivolumab monotherapy group ( n=316 ) received Nivolumab 3 mg/kg Q2W plus placebo.
Patients in the Ipilimumab monotherapy group ( n=315 ) received Ipilimumab 3 mg/kg Q3W for four doses plus placebo.
Patients were treated until progression or unacceptable toxic effects.
Overall survival and progression-free survival were dual endpoints of the trial. Secondary endpoints included objective response rates ( ORR ), descriptive efficacy assessments and safety.
The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 106,110 new diagnoses of melanoma and about 7,180 related deaths are estimated for 2021.
Globally, the World Health Organization ( WHO ) estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths.
Melanoma is mostly curable when treated in its very early stages; however, survival rates decrease if regional lymph nodes are involved. ( Xagena )
Source: BMS, 2021