Niraparib Triplet Shows PFS Benefit vs Atezolizumab as ES-SCLC Maintenance

Efficacy data revealed that patients treated with the triplet therapy experienced a median PFS of 4.9 months vs 1.8 months with atezolizumab alone.

The addition of niraparib (Zejula) and temozolomide (Temodar) to atezolizumab (Tecentriq) exhibited advantageous progression-free survival (PFS) outcomes vs atezolizumab alone as maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC) who achieved at least a partial response following 4 to 6 cycles of frontline platinum-based chemotherapy, according to findings from a phase 1b/2 trial (NCT03830918) presented at the IASLC 2025 World Conference on Lung Cancer (WCLC).1

Efficacy data revealed that patients treated with the triplet therapy (n = 19) experienced a median PFS of 4.9 months (95% CI, 1.9-9.0) vs 1.8 months (95% CI, 1.5-1.9) with atezolizumab alone (n = 16; P = .0024). Additionally, the median overall survival (OS) was 12.0 months (95% CI, 6.4-24.1) vs 9.1 months (95% CI, 3.2-13.1) in each respective arm. Notably, 2 patients were still receiving ongoing treatment in the triplet arm, and an additional 2 patients were alive and in follow-up at data cut-off.

“Niraparib, temozolomide and atezolizumab demonstrates a PFS benefit over atezolizumab alone with mostly low-grade toxicities,” Jonathan W. Goldman, MD, a professor of Medicine in the Hematology/Oncology Division of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, concluded in the presentation with study coinvestigators.1 “This adds to the growing data supporting PARP inhibitor plus low-dose temozolomide in SCLC, either in the maintenance or refractory setting. Future biomarker analysis includes correlation of efficacy with SLFN11 expression and with markers of DNA damage repair.”

Following first-line chemotherapy, patients with ES-SCLC were randomly assigned to receive the niraparib-based triplet or atezolizumab alone within 7 weeks of day 1 of the last cycle of chemotherapy.In the phase 1b safety lead-in portion of the trial, 16 patients were given 200 mg of oral daily niraparib, 30 mg of temozolomide on days 1 to 5, and 1680 mg of atezolizumab in 4-week cycles. In the phase 2 portion of the trial, 35 patients were randomly assigned 1:1 to receive the same dosing schedule of the triplet or atezolizumab at 1680 mg every 4 weeks, stratified by history of brain metastases.

In the combination and control arms, respectively, the median age was 67 years (range, 48-81) vs 69.5 years (range, 54-90), and most patients were White (73.7% vs 75.0%) and non-Hispanic (79.0% vs 81.3%). Most patients had a history of smoking (89.5% vs 81.3%). A total of 36.8% vs 75.0% of patients had a history of brain metastases.

The primary end points of the phase 1b and 2 portions of the trial were the recommended phase 2 dose of niraparib/temozolomide and PFS per RECIST v1.1 criteria.2 Secondary end points included objective response rate, OS, and the incidence of adverse effects per CTCAE v4.0 criteria.

In the triplet arm, the most common any-grade treatment-emergent AEs (TEAEs) included fatigue and nausea (both 31.6%), followed by anemia (26.3%) and platelet count decreases (21.1%). Additionally, the most common grade 3 or higher TEAEs included anemia, fatigue, platelet count decreases, and hypertensions (all 10.5%), followed by oral mucositis and maculo-papular rash (both 5.3%).

Investigators initiated this trial to assess the addition of PARP inhibition with temozolomide to atezolizumab, which has previously shown promise in extending survival in SCLC. Although approximately 60% of patients respond to first-line platinum-etoposide therapy, the authors noted that duration of response remains short even with PD-L1 inhibition; recurrence typically occurs within 3 months of chemotherapy.

References

1. Goldman JW, Abdel-Karim IA, Park DJ, et al. Final analysis of phase Ib/II trial of niraparib/temozolomide with atezolizumab vs. atezolizumab as maintenance for ES-SCLC. Presented at the International Association for the Study of Lung Cancer World Conference on Lung Cancer 2025; September 6-9, 2025; Barcelona, Spain. Abstract P3.13.35.
2. Niraparib, temozolomide and atezolizumab in treating patients with advanced solid tumors and extensive-stage small cell lung cancer with a complete or partial response to platinum-based first-line chemotherapy. ClinicalTrials.gov. Updated February 24, 2025. Accessed September 15, 2025. https://tinyurl.com/2s4e38z2