KEY TAKEAWAYS
- The LUNAR phase III trial aimed to analyze outcomes for ICI-treated patients in the LUNAR study based on PD-L1 status.
- The primary endpoint was OS. Key secondary endpoints were OS in ICI and docetaxel subgroups.
- The result demonstrated that combining TTFields with SOC in ICI-treated NSCLC patients significantly boosted survival, potentially amplified by higher PD-L1 expression levels.
Tumor Treating Fields (TTFields) electric fields targeting cancer cell survival improve overall survival(OS) in advanced lung cancer when added to standard therapy (immunotherapy or chemotherapy). This benefit is especially strong in patients receiving immunotherapy, with minimal side effects.
For this study, researchers aimed to analyze outcomes for immune checkpoint inhibitor(ICI)-treated patients in the LUNAR study based on PD-L1 status, a key biomarker for immunotherapy response.
Adults with metastatic non-small cell lung cancer (mNSCLC) experiencing progression after platinum therapy (prior ICI allowed) and with ECOG performance status ≤2 were randomly assigned in a 1:1 ratio to receive TTFields plus standard of care (SOC) or SOC alone.
TTFields at 150 kHz were administered continuously until disease progression or intolerable toxicity. The primary endpoint was OS, with key secondary endpoints including OS in subgroups receiving ICI or docetaxel.
Of 276 randomized patients, 134 (49%) allocated to receive an immune checkpoint inhibitor (ICI) had a median age of 65 years (range 23 to 86), 66% were male, 55% had non-squamous NSCLC, 4% had received ≥two prior lines of systemic therapy, and 2% had a prior ICI. Of these, 76 patients (57%) had a PD-L1 tumor proportion score (TPS) available.
In PD-L1 TPS <1% patients (n=28), the median overall survival (mOS) was 9.6 (1.9-28.2) months with TTFields/ICI (n=12) vs 9.1 (5.8-16.2) months with ICI (n=16); HR 0.98 [95% CI 0.42-2.24]; P=0.95. In PD-L1-positive patients (TPS 1-100%; n=48), OS was significantly longer with TTFields/ICI vs ICI: mOS 23.6 (7.7-not reached) months (n=22) vs 10.5 (7.5-26.6) months (n=26); HR 0.49 (95% CI 0.24-0.999); P=0.045.
There was an apparent trend toward a relationship between increasing PD-L1 expression and improved survival with TTFields and ICI vs ICI, with mOS in the intermediate PD-L1 subgroup (TPS 1-49%; n=35) of 19.0 vs 9.7 months (HR 0.55 [95% CI 0.25-1.22]) and, in the high PD-L1 subgroup (TPS >50%; n=13), not reached vs 30.0 months (HR 0.17 [95% CI 0.02-1.46]).
Adverse event frequencies were comparable between TTFields/ICI (97%) and ICI (88%) groups, including pneumonitis (3% vs 6%). TTFields-related adverse events occurred in 70% of ICI-treated patients, most being grade 1/2 local skin irritation; 5% reported a grade 3 adverse event. No grade 4 adverse events or deaths were attributed to TTFields.
The result demonstrated that combining TTFields with SOC in ICI-treated NSCLC patients significantly boosted survival, potentially amplified by higher PD-L1 expression levels.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/952
Clinical Trial: https://clinicaltrials.gov/study/NCT02973789
Leal T, Kotecha R, Ramlau R, Zhang L, Milanowski J, Cobo M, Roubec J, Petruzelka L, Havel L, Kalmadi S, Ward J, Andric Z, Berghmans T, Gerber DE, Kloecker G, Panikkar R, Aerts J, Delmonte A, Pless M, Greil R, Rolfo C, Akerley W, Eaton M, Iqbal M, Langer C. TTFields and Immune-Checkpoint Inhibitor in Metastatic Non-Small Cell Lung Cancer: PD-L1 Subgroups in the Phase 3 LUNAR Study.
