CHICAGO – Surgical resection is an effective treatment in selected patients with advanced melanoma treated with checkpoint blockade immunotherapy, according to a study of an institutional database at Memorial Sloan Kettering Cancer Center in New York presented at the Society of Surgical Oncology Annual Cancer Symposium.
“In the era of improved systemic therapy, checkpoint blockade for metastatic melanoma and the ability to surgically resect all disease after treatment is associated with an estimated survival of 75%, better than what’s been previously reported,” said Danielle M. Bello, MD, of Memorial Sloan Kettering.
The study analyzed a cohort of 237 patients who had unresectable stage III and IV melanoma and were treated with checkpoint blockade, including CTLA-4, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 inhibitors, and then had surgical resection during 2003-2017.
Dr. Bello noted two previous studies that had reported encouraging outcomes in advanced melanoma. The first highlighted the role for surgery in stage IV melanoma. In that phase 3 clinical trial, patients had resection of up to five sites of metastatic disease and were then randomized to one of two treatment arms: bacillus Calmette-Guérin and allogeneic whole-cell vaccine (Canvaxin) or bacillus Calmette-Guérin and placebo. While this trial found no difference in overall survival between groups, it did report a 5-year overall survival exceeding 40% in both treatment arms, which highlighted that Stage IV patients who underwent resection of all their disease had survival outcomes superior to outcomes previously reported (Ann Surg Onc. 2017 Dec;24[13]:3991-4000). The second trial, the recent Checkmate 067 trial, emphasized the role of effective systemic checkpoint blockade in advanced stage III and IV melanoma. It reported that patients treated with combined nivolumab/ipilimumab therapy had not reached median overall survival at minimum 36 months of follow-up (N Engl J Med. 2017 Oct 5;377[14]:1345-56).
“We know that checkpoint inhibitor therapy has revolutionized the landscape of unresectable stage III and IV melanoma,” Dr. Bello said. However, despite encouraging trial readouts of overall survival, progression-free survival is a different story. “We know that the median progression-free survival even in our best combination therapy is 11.5 months, meaning that 50% of patients will go on to progress in a year and many will go on to surgical resection of their disease and do quite well,” she said.
Dr. Bello and her coauthors set out to describe outcomes of a “highly selective group” of patients who had surgical resection after checkpoint inhibitor therapy. “The majority of patients in our study had a cutaneous primary melanoma,” she said. Median age was 63 years, and 88% had stage IV disease. Regarding checkpoint blockade regimen, 62% received anti–CTLA-4, and 29% received combination anti–PD-1 and anti–CLTA-4 either sequentially or concomitantly prior to resection.
The median time from the start of immunotherapy to the first operation was 7 months. Forty-six percent had no further postoperative treatment after resection. In those, who did require further treatment, the majority received anti–PD-1 followed by targeted BRAF/MEK therapy, she said.