Atezolizumab Plus Chemoradiation Provides No Survival Benefit in LS-SCLC

Atezolizumab (Tecentriq) administered concurrently with chemoradiation (CRT) failed to improve overall survival (OS) and progression-free survival (PFS) outcomes compared with standard chemoradiation alone in patients with limited-stage small cell lung cancer (LS-SCLC).

Results from the phase 3 NRG-LU005 trial (NCT03811002), which were presented at the 2024 ASTRO Annual Meeting, showed that the median OS was 39.5 months (95% CI, 27.5-not reached [NR]) with concurrent CRT alone vs 33.1 months (95% CI, 27.8-43.9) with the addition of atezolizumab (HR, 1.11; 95% CI, 0.85-1.45; P = .7640). The median PFS was 11.5 months (95% CI, 10.7-13.4) and 12.0 months (95% CI, 10.8-15.1) in each respective arm (HR, 1.00; 95% CI, 0.80-1.25; P = .9542).

Data also showed a median distant metastasis–free survival (DMFS) of 13.2 months (95% CI, 11.3-18.2) with concurrent CRT only and 16.8 months (95% CI, 12.0-23.5) with CRT plus atezolizumab (HR, 0.95; 95% CI, 0.75-1.21; P = .6895). The addition of atezolizumab to concurrent CRT also did not significantly impact time to local failure (HR, 0.95; 95% CI, 0.75-1.21; P = .6305).

According to presenting author Kristin A. Higgins, MD, chief clinical officer at City of Hope Cancer Center Atlanta, OS and PFS outcomes were typically better with concurrent CRT alone across patient subgroups defined by characteristics such as T-stage, ECOG performance status, and radiotherapy fractionation.

When looking at OS in an unadjusted analysis for radiation schedule comparison, investigators unveiled preliminary findings that patients may have received twice-daily radiation vs once-daily schedule, which may have done in patients with better performance status, among other reasons.

When stratifying patients based on whether they received radiation twice daily at 45 Gy or once daily at 66 Gy, there were no statistically significant differences in OS between the CRT alone and atezolizumab/CRT arms (HR, 1.13; 95% CI, 0.87-1.48; P = .3487).

Additionally, when using twice-daily fractionation as the reference, once-daily radiotherapy yielded a more notable difference in OS outcomes (HR, 1.45; 95% CI, 1.10-1.89; P = .0075). Regardless of atezolizumab administration, preliminary data showed that the median OS for patients who received twice-daily radiotherapy was 35.4 months (95% CI, 32.3-NR) vs 28.3 months (95% CI, 21.7-40.6) with once-daily radiation (HR, 1.44; 95% CI, 1.10-1.89).

“Concurrent atezolizumab did not improve [OS] for patients with [LS-SCLC] compared with standard [CRT],” Higgins said. “Twice-daily radiation did show improved survival and could be the optimal choice of radiation fractionation.”

In the international NRG-LU005 trial, 544 patients were randomly assigned 1:1 to receive platinum/etoposide every 3 weeks for 3 cycles plus thoracic radiotherapy at 45 Gy twice daily or 66 Gy daily with or without atezolizumab intravenously. Patients were then given atezolizumab every 3 weeks for up to 1 year until unacceptable toxicity or disease progression, or observation.

The trial’s primary end point was OS. Secondary end points included PFS, objective response rate, DMFS, toxicities, quality of life, quality-adjusted survival, fatigue, and biomarkers.

Patients with stage Tx, T1 to T4, N0 to N3, M0 LS-SCLC, a, ECOG performance status of 0 to 2, and 1 cycle of chemotherapy prior to registration were eligible for enrollment on the trial. Stratification factors included radiation schedule (twice daily vs daily), receipt of cisplatin or carboplatin, gender, and performance status (0-1 vs 2).

The median age was 67 years (range, 20-85) in the CRT-alone arm (n = 270) and 66 years (range, 44-84) in the CRT/atezolizumab arm (n = 274). Most patients in each respective arm were female (50.7% vs 51.1%), had an ECOG performance status of 1 (50.4% vs 51.8%), were former smokers (68.4% vs 65.9%), were White (81.9% vs 78.5%), and non-Hispanic or Latino (95.2% vs 95.3%). Additionally, most patients had T1 disease (35.2% vs 32.5%), N2 disease (54.4% vs 54.0%), stage IIIA disease (39.6% vs 40.9%), receipt of cisplatin (58.9% vs 59.5%), and once-daily radiotherapy (52.6% vs 52.9%).

Most patients in the CRT alone and CRT/atezolizumab arms, respectively, had any-grade adverse effects (AEs; 99.0% vs 99.6%) and grade 3/4 AEs (92.5% vs 86.5%). AEs that led to death occurred in 1.6% and 9.0% of patients from each arm. There were 4 grade 5 immune-related AEs in the CRT/atezolizumab arm.

Of note, 94.0% and 97.4% of patients from the CRT alone and CRT/atezolizumab arms, respectively, received any protocol treatment, and 92.9% and 92.5% from each arm completed a full course of radiotherapy. Any-grade pneumonitis affected 11.8% and 26.2% of patients in each respective arm; 3.2% and 4.9% of patients had grade 3/4 pneumonitis. Investigators reported grade 5 pneumonitis in 2 patients who received CRT plus atezolizumab.

Disclosures: Higgins cited RefleXion Medical, AstraZeneca, Janssen Pharmaceuticals, Genentech, and Jazz Pharmaceuticals as her disclosures.

Reference

Higgins KA, Hu C, Ross HJ, et al. Concurrent chemoradiation +/– atezolizumab (atezo) in limited-stage small cell lung cancer (LS-SCLC): results of NRG Oncology/Alliance LU005. Presented at: 2024 American Society for Radiation Oncology Annual Meeting; September 29-October 2, 2024; Washington, DC. Abstract LBA02.