Bristol-Myers Squibb pioneered the use of immune checkpoint inhibitors for the adjuvant treatment of melanoma, beginning with Yervoy.
Five-year overall survival data from the phase 3 CA184-029 trial were recently added to the prescribing information for Yervoy for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.
In the trial, 65% of patients treated with Yervoy were alive at five years, compared with 54% of patients who received placebo ( HR: 0.72; 95% CI: 0.58-0.88; p less than 0.002 ).
This analysis was conducted at a median follow-up of 5.3 years.
The phase 3 CA184-029 trial, a randomized ( 1:1 ), double-blind, placebo-controlled study, investigated the use of Ipiòimumab for the adjuvant treatment of melanoma.
A total of 951 enrolled patients with resected stage IIIA ( more than 1 mm nodal involvement ), IIIB and IIIC ( with no in-transit metastases ) melanoma received either Ipilimumab 10 mg/kg ( n=475 ) or placebo ( n=476 ) every three weeks for four doses, followed by every 12 weeks from week 24 to week 156 or until documented disease recurrence or unacceptable toxicity.
The major efficacy outcomes were independent review committee-assessed relapse-free survival ( RFS ) and overall surival ( OS ).
Ipilimumab has reduced the risk of recurrence or death by 25% versus placebo ( HR: 0.75; 95% CI: 0.64 to 0.90; p less than 0.002 ).
Median RFS was 26 months for Ipilimumab ( 95% CI: 19 to 39 ) and 17 months for placebo ( 95% CI: 13 to 22 ).
There were 234 RFS events in the Ipilimumab arm ( 49% of patients; 220 recurrences, 14 deaths ) and 294 events in the placebo arm ( 62% of patients; 289 recurrences, 5 deaths ).
In the CA184-029 trial, severe to fatal immune-mediated adverse reactions were reported, and included enterocolitis ( 16% ), hepatitis ( 11% ), endocrinopathy ( 8% ), hypopituitarism ( 7% ), dermatitis ( 4% ), neuropathy ( 1.7% ), hyperthyroidism ( 0.6% ), meningitis ( 0.4% ), primary hypothyroidism ( 0.2% ), myocarditis ( 0.2% ), pericarditis ( 0.2% ), pneumonitis ( 0.2% ), and uveitis ( 0.2% ).
The most common adverse reactions were rash ( 50% ), diarrhea ( 49% ), fatigue ( 46% ), pruritus ( 45% ), headache ( 33% ), weight loss ( 32% ), nausea ( 25% ), pyrexia ( 18% ), colitis ( 16% ), decreased appetite ( 14% ), vomiting ( 13% ), and insomnia ( 10% ).
Ipilimumab was discontinued for adverse reactions in 52% of patients. ( Xagena )
Source: BMS, 2017