Durvalumab Consolidation Following Chemoradiation Offers “Game-Changing” Results in Small Cell Lung Cancer

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 phase 3 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 median PFS was 16.6 versus 9.2 months, respectively, announced David R. Spigel, MD, at the 2024 ASCO Annual Meeting (abstract #LBA5).

ADRIATIC is the first phase 3 trial to show benefit with 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 Dr Spigel, chief scientific officer at Sarah Cannon Research Institute and lead investigator.

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, and the 5-year survival rate is 29% to 34%.

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%.

Results from the first planned interim analysis of ADRIATIC showed a 27% reduction in the risk of 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% for placebo.

The ADRIATIC trial randomized 530 patients with stage I-III LS-SCLC who had not progressed following cCRT to 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.)

The risk of disease progression or death was reduced by 24% (HR, 0.76; P=.0161) with durvalumab versus placebo at a median follow-up of 27.6 months. 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,” said 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 invited discussant Lauren Averett Byers, MD, MSc, The University of Texas MD Anderson Cancer Center, Houston. She called the results a “huge step forward in 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 in an unselected patient population with durvalumab consolidation, with an average OS improvement of about 2 years, is “striking” and can be considered a “game changer,” she added. “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 said.

Durvalumab was well tolerated, and the side effect profile was consistent with that of immunotherapy, said Dr Spigel.