First, the study lacked a control group, making it difficult to determine if the results represent a real advance.
“In Merkel cell it is difficult to do randomized studies because the disease is relatively uncommon, often diagnosed late, and often diagnosed in an older group of patients with a lot of comorbid problems,” Dr Kaufman said.
The results of this phase 1/2 study, though, document a high pCR rate, and that pCR correlated with relapse-free survival.
“This suggests that it is a meaningful endpoint and that a randomized study would be well positioned to show differences and would have an easy endpoint of pCR rate as an appropriate surrogate endpoint,” Dr Kaufman said.
Dr Topalian agreed with this caveat, adding that it will not be possible to compare outcomes of neoadjuvant nivolumab with standard of care without a randomized clinical trial; however, she said that it is not clear that such a study will necessarily even be done.
Another question related to the study results is the role of radiation in the treatment of these patients. Currently, patients undergoing surgery for resectable MCC would commonly undergo adjuvant radiation therapy.
In their discussion of the results, Dr Topalian and colleagues wrote, “there were no tumor relapses after pCR/MPR [major pathologic response], suggesting that standard adjuvant radiotherapy may not be needed in responders.”
Dr Kaufman pointed out that some patients in the study, including some with a pCR, went on to receive standard adjuvant radiotherapy.
“It was unclear if that was standardized or physician preference, but it could have played a role in outcomes of this as well,” he said.
Dr Topalian said that despite the positive results from this study, there are still many unknowns. In the future, she would like to test the optimal duration of neoadjuvant treatment, use of continued anti–PD-1 treatment in the adjuvant setting, the combination of anti–PD-1 therapy with other treatments, and biomarkers to predict which patients are most likely to benefit.
“It is possible that some of these questions will be answered in other cancer types that are more common, and that information will be brought to bear on the Merkel cell carcinoma situation,” Dr Topalian said. “But it is also possible that each cancer type is going to have its own specific considerations for optimizing treatment strategies.”
Topalian SL, Bhatia S, Amin A, et al. Neoadjuvant nivolumab for patients with resectable Merkel cell carcinoma in the CheckMate 358 trial [published online April 23, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.00201