Consolidation Durvalumab Shows Consistent Survival Benefit in LS-SCLC Regardless of Prior PCI and CRT Components

Consolidation therapy with durvalumab (Imfinzi) generated a statistically significant and consistent improvement in overall survival (OS) and progression-free survival (PFS) vs placebo in patients with limited stage small cell lung cancer (LS-SCLC), regardless of prior exposure to prophylactic cranial irradiation (PCI) or concurrent chemoradiotherapy (CRT) components, according to findings from a post hoc analysis of the phase 3 ADRIATIC trial (NCT03703297) presented during the 2024 ESMO Congress.¹

Regarding patients with prior PCI in the durvalumab (n = 142) and placebo arms (n = 143), the median OS was not reached (NR; 95% CI, 43.9-not evaluable [NE]) and 42.5 months (95% CI, 33.4-NE) in each group (HR, 0.75; 95% CI, 0.52-1.07; multivariate HR, 0.72; 95% CI, 0.50-1.03). The 36-month OS rates were 62.1% vs 56.5%, respectively. Among patients who had no prior PCI in the durvalumab (n = 122) and placebo arms (n = 123), data showed a median OS of 37.3 months (95% CI, 24.3-NE) and 24.1 months (95% CI, 18.8-31.1) in each arm (HR, 0.71; 95% CI, 0.51-0.99; multivariate HR, 0.73; 95% CI, 0.52-1.02). After 3 years, the OS rates were 50.2% with durvalumab vs 37.3% with placebo.

Among patients with prior PCI in the durvalumab and placebo arms, the median PFS was 28.2 months (95% CI, 16.8-44.2) vs 13.0 months (95% CI, 9.2-17.0), respectively (HR, 0.73; 95% CI, 0.52-1.00; multivariate HR, 0.72; 95% CI, 0.52-0.99). The 24-month PFS rates in each group were 54.6% and 38.5%. Among those without prior PCI, the median PFS was 9.1 months (95% CI, 7.3-14.3) vs 7.4 months (95% CI, 5.7-9.2) in each arm (HR, 0.80; 95% CI, 0.59-1.09; multivariate HR, 0.84; 95% CI, 0.61-1.15). At 2 years, the PFS rates were 37.1% vs 29.3% in each arm.

Among those who received carboplatin in the durvalumab (n = 91) and placebo arms (n = 88), the median OS was NR (95% CI, 42.5-NE) and 33.4 months (95% CI, 21.7-NE) in each arm (HR, 0.56; 95% CI, 0.35-0.89; multivariate HR, 0.55; 95% CI, 0.35-0.87). At 3 years, OS rates were 65.3% vs 46.7% in each arm. Regarding patients who received cisplatin in the durvalumab (n = 173) and placebo arms (n = 178), the median OS was 41.9 months (95% CI, 27.7-NE) vs 34.3 months (95% CI, 25.4-40.7) in each arm (HR, 0.82; 95% CI, 0.61-1.10; multivariate HR, 0.81; 95% CI, 0.60-1.08). The 3-year OS rates were 52.1% and 48.1%, respectively.

Regarding PFS in the carboplatin subgroups, the median PFS was 27.9 months (95% CI, 11.1-38.7) in durvalumab arm vs 9.2 months (95% CI, 5.8-14.6) in the placebo arm (HR, 0.61; 95% CI, 0.41-0.90; multivariate HR, 0.60; 95% CI, 0.40-0.88). At 2 years, the PFS rates were 54.8% vs 33.2%, respectively. Among patients who received cisplatin, the median PFS was 11.4 months (95% CI, 9.0-23.4) vs 9.7 months (95% CI, 7.4-13.3) in each arm (HR, 0.86; 95% CI, 0.65-1.13; multivariate HR, 0.89; 95% CI, 0.67-1.17). The 2-year PFS rates were 41.8% with durvalumab and 34.8% with placebo.

Among patients who received 45 Gy of radiation twice daily over 3 weeks in the durvalumab (n = 69) and placebo (n = 79) arms, the median OS was NR (95% CI, NE-NE) vs 44.8 months (95% CI, 29.4-NE) in each group (HR, 0.68; 95% CI, 0.40-1.14; multivariate HR, 0.71; 95% CI, 0.42-1.18). The 3-year OS rates were 65.8% vs 57.4% with durvalumab and placebo, respectively. Regarding those who received radiotherapy at 60 to 66 Gy once daily for 6 weeks in the durvalumab (n = 195) and placebo arms (n = 187), the median OS was 41.9 months (95% CI, 32.0-NE) vs 26.1 months (95% CI, 21.7-36.8), respectively (HR, 0.72; 95% CI, 0.55-0.96; multivariate HR, 0.73; 95% CI, 0.55-0.96). At 3 years, the respective OS rates were 53.1% vs 43.3%.

In the twice-daily radiotherapy groups, the median PFS was 38.7 months (95% CI, 22.7-NE) with durvalumab vs 14.3 months (95% CI, 9.1-28.1) in the placebo arm (HR, 0.72; 95% CI, 0.45-1.13; multivariate HR, 0.73; 95% CI, 0.46-1.14). The 2-year PFS rates were 60.5% vs 42.9% in each arm. Among patients who received once-daily radiotherapy, the median PFS was 11.4 months (95% CI, 9.0-19.5) with durvalumab vs 7.8 months (95% CI, 6.4-11.5) with placebo (HR, 0.77; 95% CI, 0.60-1.00; multivariate HR, 0.79; 95% CI, 0.61-1.03). At 2 years, the PFS rates were 41.0% vs 30.3% with durvalumab and placebo, respectively.

“The magnitude of benefit with durvalumab vs placebo was consistent within the PCI and radiotherapy subgroups and varied somewhat between the chemotherapy subgroups. Multivariate analyses showed no significant interactions between durvalumab treatment effect and PCI or concurrent [CRT] subgroups,” Suresh Senan, MRCP, FRCR, PhD, a professor of Clinical Experimental Radiotherapy at the Amsterdam University Medical Centers (VUmc location) in The Netherlands, said in a presentation on these data. “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].”

In the ongoing, double-blind, international ADRIATIC trial, 730 patients with stage I to III LS-SCLC were randomly assigned to receive durvalumab monotherapy (n = 264), placebo (n = 266), or durvalumab plus tremelimumab (Imjudo; n = 200). In this post hoc analysis of outcomes in the durvalumab and placebo arms, investigators assessed PFS, OS, and safety in prespecified subgroups based on prior PCI use and variables associated with concurrent CRT.

In each subgroup, investigators conducted multivariate analyses in which the HRs for durvalumab vs placebo were determined via an unstratified multivariate Cox proportional hazards model using a treatment-by-subgroup interaction adjusting for factors including PCI, chemotherapy, radiotherapy, time from concurrent CRT to randomization, age, sex, performance status, and disease stage.

Of note, 35% and 34% of patients in the durvalumab and placebo arms, respectively, were 65 years or older in the PCI subgroup compared with 45% and 45% in the non-PCI group. Additionally, most patients in each treatment arm received radiotherapy once daily in the PCI (66% vs 62%) and non-PCI groups (83% vs 80%). Additionally, a higher proportion of patients were 65 years and older in the carboplatin (49% vs 59%) subgroup compared with the cisplatin subgroup (34% vs 29%) and the intent-to-treat (ITT) population (39% vs 39%). Data also showed that more patients in the twice-daily radiotherapy group received PCI (70% vs 70%) compared with those in the once-daily radiotherapy subgroup (48% vs 47%) and the ITT population (54% vs 54%).

In terms of safety in the durvalumab and placebo arms, respectively, the rate of grade 3/4 treatment-emergent adverse effects (TEAEs) were higher in the PCI group (28.4% vs 29.6%) vs non-PCI group (19.8% vs 17.9%), higher in the carboplatin (31.5% vs 31.8%) vs cisplatin group (20.8% vs 20.3%), and higher in the once-daily radiation (26.4% vs 24.7%) vs the twice-daily radiation group (18.8% vs 22.8%). Overall, rates of TEAEs leading to treatment discontinuation were comparable across subgroups, and investigators reported no meaningful differences in safety outcomes across the once-daily and twice-daily radiotherapy groups.

Reference

Senan S, Spigel D, Cho BC, et al. Durvalumab as consolidation therapy in limited-stage SCLC (LS-SCLC): outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial. Presented at the 2024 European Society for Medical Oncology Congress (ESMO); September 13-17, 2024; Barcelona, Spain. LBA81.