ADRIATIC Trial Shows Survival Benefit of Durvalumab in LS-SCLC

Durvalumab as a consolidation treatment after concurrent platinum-based chemoradiotherapy (cCRT) has shown “a statistically significant and clinically meaningful improvement” in overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with limited-stage small cell lung cancer (LS-SCLC) in the ADRIATIC trial.

David R. Spigel, MD, chief scientific officer at the Sarah Cannon Research Institute and an investigator in the study, presented results from the first planned interim analysis of the ADRIATIC trial during a plenary session at the 2024 American Society of Clinical Oncology Annual Meeting.

“The ADRIATIC results represent a breakthrough in limited-stage small cell lung cancer, a highly aggressive disease where recurrence rates are high and only 15% to 30% of patients survive 5 years,” Dr. Spigel said in a news release about the data. “Durvalumab is the first systemic treatment to show improved survival for these patients in decades and should become a new standard of care in this setting.”

Officials from AstraZeneca, the manufacturer of the drug, also weighed in on the study and its implications for the LS-SCLC treatment landscape.

“The strong improvement in [OS] seen with Imfinzi after concurrent chemoradiotherapy is transformative in the treatment of [LS-SCLC],” Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, said in the news release. “These tremendous results underscore our ambition to drive up survival rates in this earlier-stage lung cancer setting, and we look forward to working with regulatory authorities to bring Imfinzi to these patients as quickly as possible.”

The phase 3 trial evaluated durvalumab plus or minus tremelimumab in 730 patients with stage I-III LS-SCLC who had not progressed after cCRT. The trial was a double-blinded and placebo-controlled global study. The study investigators randomized patients 1 to 42 days after cCRT to receive durvalumab 1500 mg plus placebo, durvalumab 1500 mg plus tremelimumab 75 mg, or placebo plus placebo every 4 weeks for 4 cycles. This regimen was followed by durvalumab in the patients who did not receive double placebo and was followed by placebo in those who did receive double placebo. Patients received the continued durvalumab or placebo every 4 weeks for a maximum of 24 months, until investigator-determined progression or intolerable toxicity.

The first 600 patients were randomized in a 1:1:1 ratio, with the remaining patients randomized 1:1 to receive durvalumab or placebo. The researchers stratified the randomization by stage (I or II vs III) and receipt of prophylactic cranial irradiation. Among the 730 patients randomized, 264 were randomized to receive durvalumab and 266 were randomized to receive placebo. The researchers explained that baseline characteristics and prior treatments were “well balanced between arms.” The radiation schedule in the durvalumab versus placebo arms was once daily in 73.9% versus 70.3% of patients, respectively. It was twice daily in 26.1% versus 29.7%, respectively, and 53.8% of patients in each arm received prophylactic cranial irradiation.

At the interim analysis, which had a data cutoff of January 15, 2024, the median duration of follow-up for OS was 37.2 months (range, 0.1-60.9 months) in censored patients. The median duration of follow-up for PFS was 27.6 months (range, 0.0-55.8 months) in censored patients.

The median OS was 55.9 months (95% CI, 37.3 to not estimable) in patients receiving durvalumab, significantly higher than the duration of 33.5 months (95% CI, 25.5-39.9) in those receiving placebo (hazard ratio [HR], HR 0.73; P=.0104). The 24-month OS rate was 68.0% in patients receiving durvalumab, compared with 58.5% in those receiving placebo. The 36-month OS rate was 56.5% in patients receiving durvalumab, compared with 47.6% in those receiving placebo.

The PFS duration was also significantly improved in those receiving durvalumab, with a median PFS of 16.6 months (95% CI,10.2-28.2), compared with 9.2 months (95% CI, 7.4-12.9) in those receiving placebo (HR, 0.76; P=.0161). The 18-month PFS rate was 48.8% in patients receiving durvalumab, compared with 36.1% in those receiving placebo. The 24-month PFS rates were 46.2% and 34.2%, respectively.

The treatment benefit was “generally consistent” across predefined patient subgroups for OS and PFS, according to the study investigators. The maximum number of grade 3 or 4 all-cause adverse events (AEs) was reported in 24.3% of patients receiving durvalumab, compared with 24.2% of those receiving placebo. AEs that led to treatment discontinuation occurred in 16.3% and 10.6%, respectively. AEs that led to death occurred in 2.7% and 1.9%, respectively.

Any grade of pneumonitis/radiation pneumonitis was reported in 38.0% of patients receiving durvalumab, compared with 30.2% of those receiving placebo. The durvalumab plus tremelimumab arm “remains blinded until the next planned analysis,” according to the study investigators.

Dr. Spigel and colleagues concluded that “these data support consolidation [durvalumab] as a new [standard of care] for [patients] with LS-SCLC who have not progressed after cCRT.”

Reference

Spigel DR, Cheng Y, Chul Cho BC, et al. ADRIATIC: durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). Abstract #LBA5. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, Illinois.