Complete Responses Can Endure Post Pembrolizumab in Metastatic Melanoma
Monday, January 8, 2018
Patients with metastatic melanoma who are treated with pembrolizumab and achieve a complete response (CR) can maintain those responses for an extended period, even after discontinuation of the therapy, according to a new study.
The immune checkpoint inhibitor pembrolizumab has offered a promising new treatment option in metastatic melanoma, a malignancy with an historically poor median overall survival. Data remain limited, however, on potential predictors of CR with pembrolizumab and on patient disposition following treatment discontinuation.
Researchers led by Caroline Robert, MD, PhD, of Institut Gustave Roussy in Paris, examined baseline characteristics and long-term follow-up of patients treated in the KEYNOTE-001 study. Of 655 total treated patients, 105 achieved a CR (16.0%), after a median follow-up of 43 months. Results of the analysis were published in the Journal of Clinical Oncology.
Of the 105 patients with a confirmed CR, 92 of them (87.6%) remained in CR after a median of 30 months. Fourteen patients (13.3%) were still receiving pembrolizumab treatment for a median of at least 40 months.
Of the 91 patients who stopped pembrolizumab therapy after a CR, 67 elected to stop treatment (63.8%) and proceeded to observation without further anticancer therapy. The median time to CR among these patients was 13 months, and the median duration of pembrolizumab therapy was 23 months. Two of those who proceeded to observation died of causes unrelated to treatment or disease (cardiac failure and aspiration), and four (6.0%) had progressive disease 5.6, 8.5, 22.8, and 37.3 months, respectively, after discontinuing pembrolizumab. Three of them began a second course of pembrolizumab; one had progressive disease after 4 months and remains alive, one continued to receive therapy after approximately 15 months, and one received the drug for 9 months before dying as a result of a malignant neoplasm progression.
In total, only 7 of the 105 patients with a CR had confirmed progressive disease. The 24-month disease-free survival rate from the declaration of CR was 90.9%; among the 67 patients who discontinued the therapy and moved on to observation, the 24-month disease-free survival rate was 89.9%.
An analysis found that baseline tumor size and PD-L1 status were relevant predictors of response in the cohort. Patients with larger tumors (5 to 90 cm) had a lower CR rate, with the exception of those with 5- to 10-cm tumors with positive PD-L1 expression. The highest rate of CR was seen in patients with small tumors who were PD-L1–positive; these patients had a CR rate of 42.7%.
“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,” the authors wrote. “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.”