medwireNews: Patients with metastatic melanoma who achieve a complete response (CR) with pembrolizumab therapy have a low risk for disease progression or death, report researchers who believe that treatment discontinuation is possible in this setting.
“[T]he prolonged CRs experienced with pembrolizumab provide hope for a cure for advanced melanoma without the need for additional treatment, a goal that seemed previously unachievable,” they write in the Journal of Clinical Oncology.
Lead author Caroline Robert (Institut Gustave Roussy, Villejuif Paris Sud, France) and team analyzed data on 655 metastatic melanoma patients enrolled in the phase Ib KEYNOTE-001 trial who received the PD-1 inhibitor at a dose of 2 or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks. Participants who achieved a confirmed CR could discontinue treatment if they had received pembrolizumab for at least 6 months, with at least two doses given after confirmation of the CR.
Over a median follow-up of 43 months, 105 (16.0%) of 655 patients achieved a CR at a median time of 12 months. At data cutoff, 91 (86.7%) complete responders had discontinued pembrolizumab, including 67 (63.8%) who chose to stop treatment and continue to observation without receiving further anticancer therapy.
Sixty-one of the responders who elected to discontinue pembrolizumab maintained a CR after remaining off-treatment for a median of 22 months, while four had progressive disease and two died.
Of the 24 patients who discontinued pembrolizumab as they were not eligible for further treatment, nine of the 12 who stopped as a result of adverse events continued to have a CR, as did six of the seven who discontinued due to their physician’s decision.
For the 105 complete responders, the estimated 24-month disease-free survival (DFS) rate from the confirmation of CR was 90.0%. And for the 67 who chose to stop treatment, the 24-month DFS rate from discontinuation was 89.9%, dropping to 85.8% when all 89 participants who ceased pembrolizumab for reasons other than progressive disease were considered.
“Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab,” summarize Robert et al, adding that this study has given rise to several unanswered questions.
They write: “The goal now is to understand the mechanisms underlying such optimal responses to therapy and the reasons for primary or secondary resistance in patients who do not experience CR.
“Additional studies are needed to evaluate the optimum duration of treatment to achieve prolonged CR, determine when to stop treatment after CR, and assess the interplay of the various factors potentially associated with CR.”
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