Durvalumab extends survival in limited-stage small-cell lung cancer
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Key takeaways:
- Patients with limited-stage small-cell lung cancer had OS, PFS improvements on durvalumab compared with placebo in phase 3 trial.
- Durvalumab showed a "very good safety profile,” according to researcher.
CHICAGO — Durvalumab conferred significant survival benefits in patients with limited-stage small-cell lung cancer following standard-of-care treatment in a randomized phase 3 trial, according to findings presented at ASCO Annual Meeting.
Patients treated with durvalumab (Imfinzi, AstraZeneca) had median OS extended 22.5 months and median PFS increased more than 7 months compared with those who received placebo.
“Consolidation durvalumab will become the new standard of care for patients with [limited-stage small-cell lung cancer] who have not progressed after concurrent chemoradiotherapy,” David R. Spigel, MD, chief scientific officer at Sarah Cannon Research Institute, said during his presentation.
Background and methodology
Concurrent chemoradiotherapy is the current standard of care for individuals with limited-stage small-cell lung cancer, but median OS for those patients is just 25 to 30 months and a 5-year survival rate of 29% to 34%, according to background information Spigel presented.
“There really have not been any major advances in the treatment of limited-stage small-cell lung cancer for several decades,” he said.
A pair of studies, PACIFIC and CASPIAN, showed durvalumab, a human monoclonal antibody that binds to PD-L1, had survival benefits in other types of lung cancer, and warranted research in limited-stage small-cell lung cancer.
The ADRIATIC trial enrolled 730 patients who had stage I to stage III limited-stage small-cell lung cancer and had not progressed following platinum-based chemoradiotherapy.
The trial — conducted at 164 centers in 19 countries — evaluated three regimens: durvalumab monotherapy, durvalumab plus the CTLA-4 antibody tremelimumab-actl (Imjudo, AstraZeneca) or placebo.
Starting 1 to 42 days after chemoradiotherapy, researchers randomly assigned the first 600 patients in a 1:1:1 ratio to one of the three study regimens. The durvalumab cohort had 264 patients, placebo had 266 and durvalumab plus tremelimumab-actl had 200.
Spigel and colleagues stratified patients based on disease stage and whether they had received prophylactic cranial irradiation.
OS (median follow-up, 37.2 months) and PFS (median follow-up, 27.6 months), served as the study’s primary endpoints.
Key secondary endpoints included PFS and OS for durvalumab plus tremelimumab-actl compared with placebo.
“This study’s statistical plan has not met a prespecified boundary for significance, so that will be revealed at a secondary analysis, but those data remain blinded,” Spigel said.
Results and next steps
The durvalumab cohort had significantly improved OS compared with placebo (HR = 0.73; 95% CI, 0.57-0.93). The treatment arm had a median OS of 55.9 months compared with 33.4 in the placebo group.
At the 3-year mark, the durvalumab cohort had a 56.5% survival rate compared with 47.6% in placebo.
The durvalumab group also had extended PFS (HR = 0.76; 95% CI, 0.61-0.95; 16.6 months vs. 9.2 months).
“The ADRIATIC trial is a landmark study and provides a new standard of care with the addition of immunotherapy for patients with early stage small-cell lung cancer who are being treated with a goal of curing their cancer,” Lauren Averett Byers, MD, professor and thoracic section chief in the department of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center, said as a discussant.
“It’s also an important study because of the magnitude of the benefit the patients receive with the addition of durvalumab consolidation with an average of improvement and overall survival around 2 years, and this is in contrast to many clinical trials in small-cell lung cancer where often the benefit may only be measured in months.”
Maximum grade 3 and 4 all-cause adverse events occurred in 24.4% of patients in the treatment cohort and 24.2% in the placebo group.
Participants in the durvalumab group had higher rates of discontinuation due to adverse events (16.4% vs. 10.6%), death (2.7% vs. 1.9%), any-grade pneumonitis or radiation pneumonitis (38.2% vs. 30.2%), and any-grade immune-mediated adverse events (32.1% vs. 10.2%).
Spigel described the regimen as having a “very good safety profile.”
Byers noted future research should focus on which subgroups benefit the most from durvalumab.
“We now know small-cell lung cancers are really different types of lung cancers, so I think one important next step will be to understand who is benefiting the most with the addition of durvalumab and how can we start thinking about personalizing treatment for the different subtypes for small-cell lung cancer to further build on this and continue to make progress for these patients,” she said.
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Spigel DR, et al. Abstract LBA3. Presented at: ASCO Annual Meeting; May 31-June 4, 2024: Chicago.
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