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Neoadjuvant pembrolizumab appears effective for resectable melanoma
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Neoadjuvant pembrolizumab followed by curative-intent resection and adjuvant therapy conferred 1-year recurrence-free survival of 55% among patients with stage III or stage IV resectable melanoma, according to study results presented at American Association for Cancer Research Annual Meeting.
Results also showed pathologic response and tumor infiltrating lymphocytes (TILs) after initial therapy could be potential biomarkers of response.
“PD-1 blockade has been a significant breakthrough in the treatment of advanced melanoma,” Alexander C. Huang, MD, researcher at Parker Institute for Cancer Immunotherapy at University of Pennsylvania, said during a presentation. “More recently, it has also shown a significant improvement in RFS. Yet, not all patients benefit from adjuvant therapy, and there is a need to develop predictive biomarkers for treatment benefit from adjuvant therapy.”
Huang and colleagues enrolled 27 patients (59% men) with resectable stage IIIb (41%), stage IIIc (56%) or stage IV (3%) melanoma.
Exclusion criteria included prior therapy with anti-PD-1 or anti-CTLA-4 agents.
Patients received a 200-mg dose of pembrolizumab (Keytruda, Merck) followed by curative-intent resection 3 weeks later. Patients then continued pembrolizumab therapy for 1 year.
All patients were able to undergo surgery with no perioperative complications.
Twenty patients had at least 1 year of follow-up or disease recurrence. One-year RFS was 55%. Of the nine patients who had recurrence, five were disease free and two remained alive with disease at data cutoff. Two patients died.
After the initial dose of pembrolizumab, 30% (n = 8) of patients had complete or near complete pathologic response, assessed at the time of resection. All eight patients remained recurrence free at the time of reporting.
Eighty percent of patients with stage IIIb and 50% of those with stage IIIc disease remained recurrence free at 1 year.
A greater proportion of patients with residual viable tumor of less than 50% at the time of resection achieved 1-year RFS than those with higher residual viable tumor (88% vs. 33%)
Researchers also assessed TILs at time of resection. Eighty-nine percent of patients with brisk TILs achieved 1-year RFS compared with 27% of those with non-brisk TILs.
“Moreover, TIL response was highly correlative with pathologic response. All patients with complete or near complete response had brisk TILs,” Huang said. “Thus, the pathologic response we see after a single dose is associated with immune cell infiltration.”
The therapy appeared well tolerated. Researchers did not observe any grade 4 or higher adverse events. Four patients discontinued treatment before 1 year due to adverse events.
“Pathologic response and TIL assessment after a single dose are predictive of DFS in the setting of adjuvant treatment,” Huang said. “Additional studies are required to further define pathologic response, TIL and their predictive value.” – by Cassie Homer
References:
Huang AC, et al. Abstract CT181. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.
Disclosures: Huang reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.