Concurrent Tecentriq Adds First Survival Benefit Seen in Small Cell Lung Cancer in 20 Years

September 25, 2018

The IMpower133 trial demonstrated the added overall and progression-free survival benefits of adjuvant Tecentriq with standard of care therapy for patients with extensive-stage small cell lung cancer.

The addition of Tecentriq (atezolizumab) to standard of care chemotherapy in the first-line setting prolonged progression-free and overall survival among patients with extensive-stage small cell lung cancer, according to study results presented at the 19th World Conference on Lung Cancer (WCLC) in Toronto, Canada.

“(SCLC) is a highly lethal disease whose management has largely been unchanged over the past 20-plus years,” said Stephen V. Liu, M.D., who is associate professor of medicine at Georgetown University and a member of the trial steering committee.

“The majority of patients present with extensive-stage disease, where the first-line standard of care remains carboplatin plus etoposide — a regimen produced in the 1980s,” he added.

The global, double-blind, randomized, placebo-controlled phase 1/3 IMpower133 trial evaluated the efficacy and safety of first-line Tecentriq as adjunctive therapy to standard of care, combination carboplatin and etoposide, in 403 treatment-naïve patients with extensive-stage small cell lung cancer.

Results from the study were also simultaneously published in the New England Journal of Medicine.

All patients received four 21-day cycles of carboplatin and etoposide. They were also randomized to receive concurrent Tecentriq (201 patients) or placebo (202 patients). Treatment was then followed by maintenance therapy with Tecentriq or placebo every three weeks until progressive disease or loss of clinical benefit.

Age, demographics and smoking status were representative of the disease: median age was 64 years in both groups and the majority were male, white and former smokers.

After follow-up for approximately 13.9 months, median overall survival was 12.3 months for those treated with Tecentriq and 10.3 months for individuals in the placebo arm, which results in a 30 percent reduction in the risk for death among those treated with the adjuvant therapy.

Similarly, median progression-free survival was 5.2 months in the Tecentriq group and 4.3 months in the placebo group for a 23 percent reduction in the risk for disease progression. Tecentriq was associated with a higher six-month progression-free survival rate (30.9 percent vs. 22.4 precent), and a more than doubled 12-month rate (12.6 percent vs 5.4 percent) compared with placebo.

The safety profile of the adjuvant therapy appeared consistent with the previously reported safety profile of the individual agents, with no new findings observed. The most common grade 1 to 2 treatment-related side effects among the Tecentriq and placebo arms included neutropenia (13.1 percent vs 10.2 percent, respectively), anemia (24.7 percent vs 20.9 percent), decreased neutrophil count (3.5 percent vs 6.1 percent), thrombocytopenia (6.1 percent vs 7.1 percent) and leukopenia (7.6 percent vs 5.1 percent).

“These data suggest that atezolizumab plus carboplatin and etoposide is a new standard of care for the first-line treatment of extensive-stage small cell lung cancer,” Liu said.

In a follow-up discussion, Natasha Leighl, M.D., MMSc, FRCPC, FASCO, from the Princess Margaret Cancer Centre in Toronto, agreed this adjuvant therapy should be the new standard of care, pending regulatory and economic thresholds. “With (a 30 percent decrease in disease progression or death), the tremendous unmet need, and the nearly four decades of lack of progress, we have a long way to go to catch up to non-small cell lung cancer, and it starts today.”

She added that checkpoint inhibitors may play an important role for small cell lung cancer in the future. “It really highlights the urgent need for progress in patient selection, biomarker research, and the need to change our culture of tissue collection and clinical trials. Finally, small cell lung cancer is a preventable disease, and we need urgent steps in tobacco control to help us eradicate this entirely.”


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