Durvalumab consolidation therapy demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with limited-stage small cell lung cancer (LS-SCLC) who had not progressed following standard-of-care concurrent chemoradiotherapy (cCRT).
Data from the ADRIATIC trial showed that the median OS in the durvalumab arm was 55.9 months compared with 33.4 months in the placebo arm, and the median PFS was 16.6 months versus 9.2 months, respectively, according to data presented at the 2024 ASCO Annual Meeting (abstract #LBA5).
ADRIATIC is the first phase 3 trial to show the benefit of immunotherapy in patients with LS-SCLC.
“Consolidation durvalumab will become the new standard of care for patients with LS-SCLC who have not progressed after cCRT,” predicted lead investigator David R. Spigel, MD, chief scientific officer at Sarah Cannon Research Institute, Nashville, TN.
No major advances in systemic treatment for LS-SCLC have occurred for several decades, he said. With the current standard of cCRT, the median OS in this population is 25 to 30 months and the 5-year survival rate is 29% to 34%.
No major advances in systemic treatment for LS-SCLC have occurred for several decades. With the current standard of cCRT, the median OS in this population is 25 to 30 months.
Results from the first planned interim analysis of ADRIATIC showed a 27% reduction in the risk for death in patients randomized to durvalumab versus placebo (hazard ratio [HR], 0.73; P=.0104), with a median follow-up of 37.2 months. The estimated median OS was 55.9 months in the durvalumab arm versus 33.4 months in the placebo arm.
An estimated 57% of patients randomized to durvalumab were alive at 3 years compared with 48% who received placebo.
The ADRIATIC trial randomized 530 patients with stage I-III LS-SCLC that did not progress following cCRT to receive durvalumab or placebo. A third arm of the trial randomized patients to durvalumab plus tremelimumab followed by durvalumab. (This arm remains blinded, and findings will be read out after the final analysis.)
At a median follow-up of 27.6 months, the risk of disease progression or death was reduced by 24% (HR, 0.76; P=.0161) with durvalumab versus placebo. An estimated 46% of patients treated with durvalumab had not experienced disease progression at 2 years, compared with 34% in the placebo arm.
The OS and PFS benefits observed with durvalumab were generally consistent across key prespecified patient subgroups, including age, sex, race, disease stage at diagnosis, prior radiation, and whether patients received prophylactic cranial irradiation.
“Durvalumab consolidation treatment for up to 2 years was well tolerated, and safety findings were consistent with the known safety profile of durvalumab monotherapy in the post-cCRT setting,” reported Dr Spigel.
The ADRIATIC study is a landmark trial that could create a new goal of curing LS-SCLC with the use of immunotherapy, said Lauren Averett Byers, MD, MSc, The University of Texas MD Anderson Cancer Center, Houston. She called the results a “huge step forward [for] patients with LS-SCLC,” adding that they could “establish a new standard of care for the first time in 40 years.”
The magnitude of benefit from durvalumab consolidation in an unselected patient population—with an average OS improvement of about 2 years—is “striking” and can be considered a “game-changer,” Dr Byers said. “This is in contrast to many clinical trials in SCLC, where often the benefit may be measured in months.”
“As we get further follow-up, we would expect that this means there are more patients being cured of [LS-SCLC],” she concluded.
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