Talazoparib extends PFS in maintenance regimen for small cell lung cancer subgroup
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Key takeaways:
- Adding talazoparib to maintenance therapy prolonged PFS in SLFN11-positive extensive-stage small cell lung cancer.
- Significantly more hematologic adverse events occurred in the combination therapy group.
CHICAGO — Adding talazoparib to atezolizumab as maintenance treatment after front-line chemoimmunotherapy significantly lengthened PFS among adults with SLFN11-positive extensive-stage small cell lung cancer, according to a phase 2 study.
Results of the randomized trial presented at ASCO Annual Meeting suggested that a biomarker-based approach to treating small cell lung cancer is feasible and should be considered in the development of novel therapies, according to the investigators.
“This study demonstrates the feasibility of conducting biomarker-selected trials in small cell lung cancer, paving the way for future evaluation of novel therapies in selected small cell lung cancer populations,” Nagla Fawzy Abdel Karim, MD, medical oncologist at Inova Schar Cancer Institute, said during a presentation.
Background
Small cell lung cancer remains the most aggressive form of lung cancer, with a 3-year survival rate of approximately 12%, according to Abdel Karim.
“Extensive-stage small cell lung cancer is often responsive to initial induction systemic therapy; however, most patients experience disease progression within a year of treatment initiation,” she said.
“Subsequent therapy outcomes remain challenging after disease progression, with responses being rare,” she added. “Consequently, continuing to improve outcomes in the first-line setting remains critical.”
Previous research has suggested that the addition of immune checkpoint inhibitors to chemotherapy can modestly extend OS, Abdel Karim said. Additionally, a retrospective analysis showed the addition of a poly (ADP-ribose) polymerase (PARP) inhibitor to chemotherapy provided additional OS and PFS benefit for patients with SLFN11-positive small cell lung cancer.
Methodology
Conducted by members of the SWOG Cancer Research Network, SWOG S1929 evaluated whether atezolizumab (Tecentriq, Genentech) — anti-PD-L1 monoclonal antibody — in combination with the PARP inhibitor talazoparib (Talzenna, Pfizer) improved survival outcomes compared with atezolizumab alone as maintenance therapy for adults with SLFN11-positive extensive-stage small cell lung cancer.
Investigators randomly assigned 106 study participants (median age, 67 years; range, 45-84; 48% women; 96% white) to receive either atezolizumab (n = 52) maintenance therapy or atezolizumab plus talazoparib (n = 54) following front-line chemotherapy.
One-quarter of patients underwent previous radiation therapy.
PFS served as the study’s primary endpoint. Secondary endpoints included objective response rate, OS and safety.
Median follow-up was 5 months (range, 0-21.5).
Key findings
Investigators reported significantly longer median PFS with the combination of atezolizumab plus talazoparib vs. atezolizumab alone (4.2 months vs. 2.8 months; HR = 0.7; 80% CI, 0.52-0.94).
Study participants who received atezolizumab alone had an ORR of 16% (80% CI, 8-27) compared with 12% (80% CI, 5-22) in the atezolizumab-talazoparib group.
Researchers noted no significant difference in median OS between the two groups, with a median OS of 8.5 months (80% CI, 7.4-12.7) for the atezolizumab group and 9.4 months (80% CI, 8.1-14.2) for the atezolizumab-talazoparib group (HR = 1.17; 80% CI, 0.8-1.71).
No treatment-related deaths occurred during the study. Three study participants discontinued treatment due to related toxicity, including one patient who received atezolizumab plus talazoparib and two patients who received atezolizumab only.
Significantly more treatment-related hematologic adverse events occurred with the combination treatment than with atezolizumab alone (50% vs. 4%; P < .001), an expected result due to the addition of talazoparib to the regimen, investigators noted.
Anemia, the most common grade 3 treatment-related adverse event, occurred in 37% in the combination maintenance therapy group vs. 2% who received atezolizumab only.
Clinical implications
The results suggest that adding talazoparib to the current standard maintenance regimen of atezolizumab prolongs PFS among patients with SLFN11-positive extensive-stage small cell lung cancer, according to Abdel Karim.
“This has been a unique collaboration in making a biomarker-based approach feasible as a step toward selected therapy in small cell lung cancer,” she said. “We are currently analyzing the association of SLFN11 expression with clinical outcomes.”
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Abdel Karim NF, et al. Abstract 8504. Presented at: ASCO Annual Meeting; June 2-6, 2022; Chicago.
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