No Survival Benefit for Tecemotide After Chemoradiotherapy in Stage III NSCLC
In the phase III START trial reported in The Lancet Oncology, Butts et al assessed whether maintenance treatment with the MUC1 antigen–specific immunotherapy tecemotide could prolong overall survival in patients with unresectable stage III non–small cell lung cancer (NSCLC) who had received chemoradiotherapy. They found no overall survival benefit with tecemotide in the entire population, but there was evidence of a survival benefit among patients who had received previous concurrent chemoradiotherapy.
Study Details
In this international double-blind trial, 1,513 patients who had completed chemoradiotherapy within 4 to 12 weeks before randomization with confirmed stable disease or objective response were randomly assigned 2:1 to receive subcutaneous injections of tecemotide (806 μg lipopeptide; n = 1,006) or placebo (n = 507) every week for 8 weeks and then every 6 weeks until disease progression or withdrawal. Patients received cyclophosphamide 300 mg/m2 (before tecemotide) or saline (before placebo) once before the first study drug administration. Patients were stratified by stage, response to chemoradiotherapy, concurrent vssequential chemoradiotherapy, and region.
In March 2010, clinical trials of tecemotide were put on hold after a case of encephalitis occurred in a phase II trial of tecemotide in multiple myeloma. Investigations of this patient, a safety analysis of tecemotide in NSCLC, and introduction of safety measures in protocol amendments led to the clinical hold being lifted in June 2010. Due to the clinical hold, 274 patients were excluded from the primary analysis population, leaving 829 patients in the tecemotide group and 410 in the placebo group as the modified intent-to-treat population. Overall survival was the primary endpoint.
The tecemotide and placebo groups were generally balanced for age (median, 61 and 61.5 years), sex (68% male in both), ethnicity (92% white in both), smoking (current in 24% in both, never in 6% in both), Eastern Cooperative Oncology Group performance status (0 in 48% and 41%, 1 in 52% and 58%), disease stage (IIIB in 61% in both), duration of disease (median, 6.2 and 6.1 months), histology (adenocarcinoma in 35% and 40%, squamous cell carcinoma in 48% and 42%), response to initial chemotherapy (objective response in 68% in both, stable disease in 32% in both), type of initial chemoradiotherapy (concurrent in 65% in both, sequential in 35% in both), and region (North America and Australia for 26% in both, western Europe for 38% in both).
Overall Survival
After a median follow-up of 39.9 months in the tecemotide group and 37.7 months in the placebo group, median overall survival was 25.6 months vs 22.3 months (adjusted hazard ratio [HR] = 0.88, P = 0.123). However, among 538 tecemotide patients and 268 placebo patients who had received concurrent chemoradiotherapy, median overall survival was 30.8 vs 20.6 months (adjusted HR = 0.78, P = .016). Among patients who had received sequential chemoradiotherapy, overall survival was 19.4 vs 24.6 months (adjusted HR = 1.12, P = .38).
Subgroup analysis among patients who had received concurrent chemoradiotherapy showed that hazard ratios consistently favored tecemotide, with significant improvements observed in white patients (median, 31.0 vs 20.4 months, HR = 0.76, P = .0091), ever-smokers (median, 32.1 vs 20.6 months, HR = 0.75, P = .0058), and patients with nonadenocarcinoma (median, 29.6 vs 19.6 months, HR = 0.77, P = .0435).
Adverse Events
The most common adverse events of any grade in the tecemotide group were cough (33% vs 28% in placebo group), dyspnea (23% vs 23%), and fatigue (19% vs 21%). Grade 3 or 4 adverse events occurring in > 2% of tecemotide patients were dyspnea (5% vs 4%), central nervous system (CNS) metastases (3% vs 1%), and pneumonia (2% vs 3%). Serious adverse events occurring in > 2% of tecemotide patients were pneumonia (3% vs 3%), dyspnea (3% vs 3%), and CNS metastases (3% vs 2%). There was no difference between groups in serious immune-related adverse events.
The investigators concluded, “We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non–small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted.”
Charles Butts, MD, of Cross Cancer Institute in Edmonton, Alberta, is the corresponding author for The Lancet Oncology article.
The study was sponsored and designed by Merck KGaA. For full disclosures of the study authors, visit www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
