There have been no major advances in the treatment of limited-stage small cell lung cancer in several decades. The standard of care is concurrent chemoradiotherapy, but even with that most patients will relapse within 2 years, and only a minority of patients will survive 5 years.
So said, David R. Spigel, MD, Chief Scientific Officer at the Sarah Cannon Research Institute in Nashville, Tennessee, as he began his presentation of findings from the ADRIATIC trial, which took place on June 1 during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
ADRIATIC, which was designed to assess the role of durvalumab as consolidation therapy following concurrent chemoradiotherapy for patients with limited-stage small cell lung cancer (SCLC), is the first phase III study to establish the role of immunotherapy in this setting, and it showed treatment with durvalumab led to a statistically significant and clinically meaningful improvement in both overall survival (OS) and progression-free survival (PFS) for these patients, Dr. Spigel said.
Indeed, according to the findings, overall survival with durvalumab consolidation treatment resulted in a hazard ratio of 0.73, which corresponds to a 27% reduction in the risk of death, with a P value of 0.0104 with a little more than 3 years of follow up. The median survival for the durvalumab arm was 55.9 months compared with 33.4 months for placebo, nearly a 2-year advantage. The 3-year landmark overall survival rates were 56.5% for durvalumab and 47.6% for placebo.
Dr. Spigel said the survival advantage for durvalumab appeared to be consistent across all predefined subsets, whether you look at age, gender, race, choice of chemotherapy used, radiation schedule, or the use of prophylactic cranial irradiation (PCI).
Durvalumab also demonstrated a statistically significant improvement in progression-free survival with a hazard ratio of 0.76, which corresponds to a 24% reduction in the risk of progression or death, and a P value of 0.0161 with a median follow-up of a little more than 2 years. The median PFS for durvalumab was 16.6 months compared with 9.2 months for the placebo arm, an advantage of about 7.4 months. The 2-year landmark PFS rates were 46.2% for durvalumab versus 34.2% for placebo.
As with survival, the benefit for PFS with durvalumab seemed to be consistent across all predefined subsets, Dr. Spigel said.
Adding context to the results, Dr. Spigel delved into the study design and safety findings.
All study participants had stage I-III limited-stage small cell lung cancer, good performance status, and all patients had received concurrent chemoradiation therapy before randomization. PCI use was at the discretion of the treating investigator. The study had dual primary endpoints of overall survival and progression-free survival assessed by blinded independent central review
Dr. Spigel said the chemotherapy used was platinum etoposide for up to four cycles and the radiation therapy could either be once daily up to 66 Gy or twice a day up to 45 Gy. All patients were randomized to either durvalumab at 1500 milligrams IV monthly for 2 years; to placebo; or to a third arm that included the combination with tremelimumab. The results of the combination arm with tremelimumab remain blinded and will be analyzed at the next planned analysis.
“About a third of the patients on the durvalumab arm and about a quarter of the patients on the placebo arm went on to receive the full 2 years of therapy,” he said. “The most common reason for not completing treatment was disease progression. About 46% of patients on the durvalumab arm and 58% on the placebo arm went on to receive additional therapy at progression.
Regarding safety, grade 3-4 adverse events were 24% in each arm. Adverse events leading to treatment discontinuation were 16.4% in the durvalumab arm compared with 10.6% in the placebo arm and grade 3-4 immune-mediated adverse events were seen in 5.3% of the durvalumab arm patients compared with 1.5% in the placebo arm.
“Radiation pneumonitis was the most common toxicity,” Dr. Spigel said. Looking more closely at pneumonitis, including pneumonitis, radiation pneumonitis, and other lung toxicities, Dr. Spigel said the all-grade pneumonitis rates were 38.2% for durvalumab versus 30.2% for placebo. Grade 3-4 event rates were 3.1% versus 2.6%, respectively. There was one grade 5 pneumonitis event on the durvalumab arm. Pneumonitis rates leading to treatment discontinuation were 8.8% and 3%, respectively.
Overall, Dr. Spigel said durvalumab consolidation treatment for up to 2 years was well-tolerated and the safety findings seemed consistent with durvalumab monotherapy following concurrent chemoradiation therapy. Given the consistency of benefit and tolerable safety profile, Dr. Spigel said he believes 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.
