In the phase II ADAPT-IT trial reported in the Journal of Clinical Oncology, Michael A. Postow, MD, and colleagues showed that findings on interim computed tomography (CT) allowed patients to avoid the third and fourth doses of combination nivolumab/ipilimumab for the treatment of advanced melanoma.
As stated by the investigators, “Nivolumab/ipilimumab is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivolumab/ipilimumab followed by nivolumab alone. Whether four doses of nivolumab/ipilimumab are needed is unclear.”
Michael A. Postow, MD
Study Details
The study included 60 patients enrolled at three U.S. centers between May 2017 and February 2019. Patients received two doses of nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) followed by CT at week 6.
Patients without new lesions or index lesion tumor growth > 4% were classified as having early favorable antitumor effect, stopped nivolumab/ipilimumab, and initiated nivolumab monotherapy. Patients without favorable antitumor effect at week 6 received the standard third and fourth doses of nivolumab/ipilimumab followed by nivolumab monotherapy.
The primary endpoint was objective response rate as evaluated by Response Evaluation Criteria in Solid Tumors version 1.1 at week 12.
Key Findings
A total of 41 patients (68%) had favorable antitumor effect at week 6 and met criteria for stopping nivolumab/ipilimumab. Among all patients, objective response rates were 48% at week 12 and 58% overall. Among patients with favorable antitumor effect, the objective response rate was 80% overall.
At a median follow-up of 25 months, the estimated 12- and 18-month progression-free and overall survival rates among all patients were 53% and 52% and 81% and 80%, respectively. Among patients with favorable antitumor effect, estimated 12-month rates (from week 6) were 68% and 85%.
Grade ≥ 3 treatment-related adverse events occurred in 57% of all patients, including 56% of patients with favorable antitumor effect and 58% without favorable antitumor effect. Grade ≥ 3 laboratory toxicity occurred in 25% of patients with favorable antitumor effect and 47% of those without it.
The investigators concluded, “The efficacy and toxicity of standard four-dose nivolumab/ipilimumab induction therapy in melanoma is likely driven by the first two doses. An interim CT scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivolumab/ipilimumab.”
Dr. Postow, of the Department of Medicine, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by the National Cancer Institute, Ludwig Collaborative and Swim Across America Laboratory, and Parker Institute for Cancer Immunotherapy. For full disclosures of the study authors, visit ascopubs.org.
