Author: By Laura Cowen, medwireNews Reporter
medwireNews: Approximately half of patients with high-risk resectable Merkel cell carcinoma (MCC) may respond to the programmed cell death protein (PD)-1 inhibitor nivolumab when given 4 weeks before surgery, show data from the phase I/II CheckMate 358 study.
Responding patients had a significantly longer recurrence-free survival (RFS) period than non-responders, with no unexpected toxicities, suggesting that the treatment “should be further explored as a potentially beneficial adjunct to surgery in patients with MCC”, write Suzanne Topalian, from the Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland, USA, and co-workers.
As reported in the Journal of Clinical Oncology, the study included 39 patients (median age 68 years, 64% men) with stage IIA–IV resectable MCC who received intravenous nivolumab 240 mg on days 1 and 15, with surgery planned for day 29.
Of these, 46.2% experienced a treatment-related adverse event (TRAE) of any grade, most commonly skin reactions (10.3%), and 7.7% experienced a grade 3 or 4 TRAE. There were no treatment-related deaths.
Among the 36 patients who underwent surgery, 47.2% achieved a pathologic complete response (pCR), defined as the absence of residual viable invasive cancer in resected tumour specimens and all sampled lymph nodes. An additional 15.4% achieved a major pathological response (MPR), defined as up to 10% residual viable tumour.
Suzanne Topalian et al also found that 54.5% of 33 evaluable patients had a radiographic response, with tumour reductions of 30% or more, and that responses were independent of tumour mutational burden and of Merkel cell polyomavirus or PD-L1 status.
At a median follow-up of 20.3 months, median RFS and overall survival were not reached among the patients who underwent surgery.
The 12- and 24-month RFS rates were 77.5% and 68.5%, respectively, but the investigators note that pathologic and radiographic responses were associated with significant 88% and 89% lower risks of recurrence at 24 months, respectively, relative to non-responses according to each criterion.
Specifically, the RFS rate at 24 months was 88.9% versus 52.2% among individuals with versus without a pCR, and 90.9% versus 48.5% among those with versus without at least 30% radiographic tumour reduction.
The investigators therefore conclude: “The possibility of tailoring the extent of surgery and/or administration of postsurgical therapy according to radiographic and pathologic response status after neoadjuvant anti–PD-1 should be examined in future MCC trials, which have the potential to be practice changing.”
They add: “Tumor markers predicting long-term clinical outcomes would be valuable to further characterize patients without pCR/MPR or radiographic regression, some of whom nevertheless have prolonged RFS and [overall survival].”
Reference
Topalian SL, Bhatia S, Amin A, et al. Neoadjuvant nivolumab for patients with resectable Merkel cell carcinoma in the CheckMate 358 trial. J Clin Oncol; Advance online publication 23 April 2020. doi: 10.1200/JCO.20.00201
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