Nivolumab + ipilimumab maintenance immunotherapy does not confer OS benefit for SCLC
Maintenance immunotherapy with the immune checkpoint inhibitors nivolumab and ipilimumab failed to improve overall survival (OS) in individuals with extensive-stage disease small-cell lung cancer (ED-SCLC), according to CheckMate 451* results presented at ELCC 2019.
The study comprised 834 individuals with ED-SCLC who did not exhibit cancer progression following four cycles of first-line platinum-based chemotherapy. Participants were randomized 1:1:1 to receive immunotherapy with nivolumab 1 mg/kg + ipilimumab 3 mg/kg Q3W (four doses, followed by nivolumab 240 mg Q2W), nivolumab 240 mg Q2W monotherapy, or placebo. Treatment ran for 2 years or until disease progression, unacceptable toxicity, or death. Minimum follow-up was 9 months. [ELCC 2019, abstract LBA1]
Nivolumab plus ipilimumab did not prolong OS compared with placebo (hazard ratio [HR], 0.92, 95 percent confidence interval [CI], 0.75–1.12; p=0.3693), nor did nivolumab monotherapy (HR, 0.84, 95 percent CI, 0.69–1.02).
“[This finding shows that] maintenance immunotherapy after successful chemotherapy [did not] improve OS … [This was] a big disappointment,” said study author Prof Taofeek Owonikoko from the Winship Cancer Institute of Emory University in Atlanta, Georgia, US.
Nonetheless, Owonikoko acknowledged that the maintenance strategy could be promising in patients who responded to immunotherapy, seeing as how some cancers treated with immunotherapy and nivolumab monotherapy took a longer time to progress. “The challenge will be how to select and identify those patients, since patients who began maintenance therapy sooner after completion of chemotherapy did appear to derive greater benefit.” Nonetheless, definitive conclusions cannot be made as this was not the primary endpoint, he added.
Identifying predictive biomarkers may help distinguish SCLC patients who might respond well to immune checkpoint inhibitor treatment, noted ELCC co-chair Dr Pilar Garrido from the Ramón y Cajal University Hospital in Madrid, Spain. “[These patients] should be assessed within prospective studies to better understand the complexity of the immune response.”
Although progression-free survival appeared to improve with immunotherapy and nivolumab monotherapy (HR, 0.72 and HR, 0.67, respectively), this cannot be considered compelling evidence of survival benefit as the primary endpoint was negative, Garrido pointed out.
Rates of all-grade toxicities were high with immunotherapy and nivolumab monotherapy (86 percent and 61 percent, respectively) leading to treatment cessation in 31 and 9 percent of those respective groups. Seven deaths were reported with immunotherapy.
“SCLC is a ‘recalcitrant’ disease and research in this field is particularly challenging for several reasons, including the rapid pace at which the disease progresses and the limited availability of tissue,” said Garrido. About 70 percent of cases are already extensive at diagnosis (ie, disease has spread beyond one lung and neighbouring lymph nodes), which cannot be treated with radiotherapy.
“This appears to be the end of the story for maintenance immunotherapy in unselected SCLC patients,” said Garrido. She called for more in-depth investigations given the negative results and the lack of data that could isolate certain subgroups who might respond to maintenance treatment.
“The commitment to high-quality research is key because we desperately need new options for SCLC … that prolong response duration and improve survival … Although there are some positive data, the final role of immune checkpoint inhibitors will be shaped by the results of ongoing trials,” said Garrido.