Durvalumab (Imfinzi) as consolidation therapy has demonstrated a statistically significant and consistent improvement in overall survival (OS) and progression-free survival (PFS) compared to placebo in patients with limited-stage small cell lung cancer (LS-SCLC), irrespective of prior prophylactic cranial irradiation (PCI) or concurrent chemoradiotherapy (CRT) components. These findings come from a post-hoc analysis of the phase 3 ADRIATIC trial (NCT03703297). The results, presented at the 2024 European Society for Medical Oncology (ESMO) Congress and the 2024 ASTRO Annual Meeting, highlight durvalumab's potential as a new standard of care in LS-SCLC.
The ADRIATIC trial, an ongoing, double-blind, international study, involved 730 patients with stage I to III LS-SCLC who were randomized to receive durvalumab monotherapy (n = 264), placebo (n = 266), or durvalumab plus tremelimumab (Imjudo; n = 200). The post-hoc analysis focused on outcomes in the durvalumab and placebo arms, assessing PFS, OS, and safety in subgroups based on prior PCI use and variables associated with concurrent CRT.
Survival Benefits Across Subgroups
In patients with prior PCI, the median OS was not reached in the durvalumab arm and was 42.5 months in the placebo arm (HR, 0.75; 95% CI, 0.52-1.07). The 36-month OS rates were 62.1% and 56.5%, respectively. Among patients without prior PCI, the median OS was 37.3 months with durvalumab and 24.1 months with placebo (HR, 0.71; 95% CI, 0.51-0.99). The 3-year OS rates were 50.2% with durvalumab and 37.3% with placebo.
For PFS, patients with prior PCI had a median PFS of 28.2 months in the durvalumab arm and 13.0 months in the placebo arm (HR, 0.73; 95% CI, 0.52-1.00). The 24-month PFS rates were 54.6% and 38.5%, respectively. Among those without prior PCI, the median PFS was 9.1 months with durvalumab and 7.4 months with placebo (HR, 0.80; 95% CI, 0.59-1.09). The 2-year PFS rates were 37.1% and 29.3% in each arm.
Impact of Chemotherapy Regimen
Patients who received carboplatin in the durvalumab arm had a median OS that was not reached, compared to 33.4 months in the placebo arm (HR, 0.56; 95% CI, 0.35-0.89). At 3 years, OS rates were 65.3% and 46.7%, respectively. For those who received cisplatin, the median OS was 41.9 months with durvalumab and 34.3 months with placebo (HR, 0.82; 95% CI, 0.61-1.10). The 3-year OS rates were 52.1% and 48.1%, respectively.
In the carboplatin subgroups, the median PFS was 27.9 months in the durvalumab arm and 9.2 months in the placebo arm (HR, 0.61; 95% CI, 0.41-0.90). At 2 years, the PFS rates were 54.8% and 33.2%, respectively. Among patients who received cisplatin, the median PFS was 11.4 months with durvalumab and 9.7 months with placebo (HR, 0.86; 95% CI, 0.65-1.13). The 2-year PFS rates were 41.8% with durvalumab and 34.8% with placebo.
Influence of Radiotherapy Schedules
For patients who received 45 Gy of radiation twice daily over 3 weeks, the median OS was not reached in the durvalumab arm and was 44.8 months in the placebo arm (HR, 0.68; 95% CI, 0.40-1.14). The 3-year OS rates were 65.8% and 57.4%, respectively. Among those who received radiotherapy at 60 to 66 Gy once daily for 6 weeks, the median OS was 41.9 months with durvalumab and 26.1 months with placebo (HR, 0.72; 95% CI, 0.55-0.96). The 3-year OS rates were 53.1% and 43.3%.
In the twice-daily radiotherapy groups, the median PFS was 38.7 months with durvalumab and 14.3 months in the placebo arm (HR, 0.72; 95% CI, 0.45-1.13). The 2-year PFS rates were 60.5% and 42.9%, respectively. Among patients who received once-daily radiotherapy, the median PFS was 11.4 months with durvalumab and 7.8 months with placebo (HR, 0.77; 95% CI, 0.60-1.00). The 2-year PFS rates were 41.0% and 30.3%.
Safety and Tolerability
The safety analysis from the ADRIATIC trial indicated a manageable safety profile for durvalumab. Any-grade adverse effects (AEs) related to pneumonitis and radiation pneumonitis occurred in 38.2% and 30.2% of patients on durvalumab and placebo, respectively. Grade 3/4 incidence of pneumonitis or radiation pneumonitis was similar between both arms, at 3.1% and 2.6%, respectively, with one grade 5 instance occurring in the durvalumab arm. Immune-mediated AE incidences were higher in the durvalumab arm, with 32.1% of patients experiencing any-grade immune-mediated AEs compared to 10.2% in the placebo arm.
Expert Commentary
Suresh Senan, MRCP, FRCR, PhD, a professor of Clinical Experimental Radiotherapy at the Amsterdam University Medical Centers (VUmc location) in The Netherlands, noted, "Durvalumab demonstrated consistent benefit vs placebo irrespective of prior PCI use and concurrent [CRT] components, further supporting consolidation durvalumab as the new standard of care in [LS-SCLC]."
Puneeth Iyengar, MD, PhD, director of the Metastatic Program of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, added, "These safety findings support the favorable risk benefit profile of consolidation durvalumab... establishing this regimen as a new standard of care for limited-stage small cell lung cancer patients."
