During the phase two confirmatory trial, physicians were allowed to administer up to four doses of neoadjuvant cemiplimab. “Patients would get two doses, undergo a scan and evaluation, and, if they were responding and not having significant side effects, they could get up to four doses,” Dr. Gross said. “The idea was that maybe we’d see more responses or push some partial responses to a more dramatic response. But we didn’t really see that.”
Explore This IssueApril 2023
Seventy-eight percent of patients received all four doses. Disease progression was the most common reason patients did not receive four doses of neoadjuvant immunotherapy. Eighty-seven percent of treated patients reported adverse events; the most common were fatigue, diarrhea, nausea, and rash. Immune-related adverse events occurred in 15% of treatment patients, with grade 3 immune-related adverse events occurring in 4% of patients. Four patients died during the trial—two of heart attacks that “were not considered related” to treatment, according to Dr. Gross; one of COVID-19; and one, age 93, of heart failure that may have been exacerbated by immunotherapy.
Fifty-one percent of patients experienced a pathological complete response; another 13% experienced a pathological major response, and “several patients … were spared function-impairing surgery,” Dr. Gross said. Two patients who presented with bulky disease at baseline experienced progression to inoperable disease (N Engl J Med. 2022;387:1557–1568).
The 63.3% rate of pathologic complete or major pathologic response is “the highest achieved in a multi-center study of single-agent anti-PD-1 neoadjuvant therapy for any solid tumor type,” according to the researchers.
Physicians (and patients) are excited about the potential of neoadjuvant immunotherapy to decrease treatment morbidity and, perhaps, improve survival. But before neoadjuvant immunotherapy can be widely adopted, some unanswered questions must be answered, including:
What impact does neoadjuvant therapy have on survival rates? This question is key to wider adoption of neoadjuvant immunotherapy, according to Kevin S. Emerick, MD, division chief of head and neck surgical oncology and co-director of the Non-Melanoma Skin Cancer Multidisciplinary Clinic and Program at Mass Eye and Ear in Boston.
“We have to make sure we’re thinking like surgical oncologists,” Dr. Emerick said. “Does neoadjuvant immunotherapy followed by surgery actually improve our overall cure rates for these patients compared to immunotherapy alone, surgery alone, or the historical approach of surgery followed by radiation?”
Additional clinical trials, including a phase 3 randomized controlled trial comparing neoadjuvant immunotherapy plus surgery and radiation, if indicated, to the current standard of care, will be necessary to answer this question. Dr. Gross said he’s currently in the process of designing a phase 3, multicenter trial.