Dr. Scott Joseph Antonia and Dr. Jedd D. Wolchok
The objective response rate for nivolumab monotherapy was 10% among all patients, and combination therapy resulted in a doubling of response.
“Although this was a small number of patients with a relatively short follow-up, I am excited about it because the early data we are seeing is that immunotherapy is probably going to have a major impact on this disease,” Scott Joseph Antonia, MD, PhD, of H. Lee Moffitt Cancer Center and Research Institute, told ASCO Daily News. “What may be distinguishing about immunotherapy is the durability of responses. It is is early yet, with just 18 months of follow-up, but we have some patients who responded and remain in response for those 18 months.”
The trial included 216 patients with advanced SCLC who had undergone prior treatment with one or more therapy including a platinum-based chemotherapy. Patients were not excluded based on PD-L1 expression or platinum sensitivity. The patients were assigned to treatment with 3 mg/kg of nivolumab twice weekly (N3; 98 patients) or nivolumab plus ipilimumab at a dose of 1 mg/kg of nivolumab (N1) plus 3 mg/kg of ipilimumab (I3; 61 patients) or N3 plus 1 mg/kg of ipilimumab (I1; 54 patients).
The overall response rates were 10% for nivolumab monotherapy, 23% for N1/I3, and 19% for N3/I1. Similar responses were seen for platinum-sensitive and platinum-refractory patients (Fig. 1).
“It is early but it appears that characteristics of response are quite similar to what we are accustomed to seeing with NSCLC, and even patients with bulky disease can respond,” Dr. Antonia said.
Responses were rapid, with the majority of responding patients showing a response by the time of the first restaging CT scan. Dr. Antonia noted that there were occasional pseudoprogressions, but it was a rare phenomenon.
The median overall survival was greatest for patients assigned to the combination treatment at 7.7 months for N1/I3 and 6.0 months for N3/I1. The median overall survival was 4.4 months for nivolumab monotherapy. The overall survival rate at 1 year was 33% for nivolumab monotherapy, 43% for N1/I3, and 35% for N3/I1.
Toxicity was similar to that seen with the drug combination in other diseases. Approximately one-half of patients treated with monotherapy had an immune-related adverse event, but only 13% had grade 3/4 toxicity. Toxicity was greater in the combination arms, with approximately three-quarters of patients experiencing some toxicity; 30% had grade 3/4 toxicity in the N1/I3 arm, and 19% had grade 3/4 toxicity in the N3/I1 arm. There were three treatment-related deaths among the patients treated with the combination. There were also two cases of limbic encephalitis, and pneumonitis occurred in 4% of patients.
In his discussion of the CheckMate 032 trial, Jedd D. Wolchok, MD, PhD, of Memorial Sloan Kettering Cancer Center, said that immunotherapy research has reached a point where the field is trying to decide what the next steps are, and combination therapies have announced themselves as the way forward. Combination therapies are not a one-size-fits-all approach, though. Dr. Wolchok applauded Dr. Antonia and colleagues for looking at different dosing regimens in their trial.
He also pointed out that, although combination immunotherapy approaches are associated with increased toxicity, the rate of grade 3/4 toxicity seen in these patients with SCLC was lower even than those of a related disease, NSCLC, indicating that the biology of each tumor microenvironment is different.
In addition, he said, “It will be useful to analyze the response rate by PD-L1 status in each group of patients. It is important that we know if there is a population of patients that benefit more from additional ipilimumab than others.”