KEY TAKEAWAYS
- The DEDICATION-1 phase 3 trial aimed to investigate if reduced-dose pembrolizumab is as effective as standard dosing in stage IV NSCLC.
- Researchers noticed a 3.2% difference in one-year survival, meeting the criteria to continue the study.
Immune checkpoint inhibitors have demonstrated improved overall survival (OS) for patients with metastatic non-small cell lung carcinoma (NSCLC). However, optimal dosing and patient selection remain under discussion. This study shows that reducing the standard dose of pembrolizumab (150-200 mg every three weeks [Q3W] or 400 mg every six weeks [Q6W]) to either 300 mg Q6W or 100 mg Q3W could maintain efficacy without compromising therapeutic outcomes.
Michel Van den Heuvel and the team aimed to assess the efficacy and safety of these reduced pembrolizumab doses in stage IV NSCLC.
Inclusive analysis was performed for an open-label non-inferiority trial comparing reduced-dose pembrolizumab (300 mg Q6W or 100 mg Q3W) with standard-dose pembrolizumab (400 mg Q6W or 150-200 mg Q3W) in patients with NSCLC eligible for pembrolizumab-based regimens.
The trial included patients receiving pembrolizumab either as monotherapy or in combination with chemotherapy. An interim analysis was preplanned after the first 250 patients were included and followed for 1 year. A clinically relevant difference of 10% in 1-year OS between arms was established as the stopping criterion for the interim analysis.
About 256 patients were analyzed in the interim review. Among the 123 patients in the standard dose group, 8 received pembrolizumab at 150 mg Q3W and 115 received it at 400 mg Q6W. In the reduced dose group of 133 patients, 5 were administered 100 mg Q3W and 128 received 300 mg Q6W. Pembrolizumab was combined with chemotherapy in 49.2% of the patients.
The 1-year OS was 56.6% (95% CI: 48.3% − 66.4%) for the standard dose and 53.4% (95% CI: 45.1% − 63.3%) for the reduced dose. Median OS was 15.9 months (95% CI: 11.8 – 23.2) for the standard dose and 13.1 months (95% CI: 10.3 – 15.4) for the reduced dose. There was no significant difference in OS between the 2 groups (P = 0.45). Median progression-free survival (PFS) was 7.3 months (95% CI: 6.3 – 9.8) for the standard dose and 7.3 months (95% CI: 5.6 – 10.8) for the reduced dose.
The study concluded that, with an observed difference in one-year survival of 3.2%, the predetermined criterion for continuing inclusion was met.
The trial was sponsored by the Radboud University Medical Center.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/105
Clinical Trial: https://clinicaltrials.gov/study/NCT04909684
Heuvel M.V.D, Noort V.V.D, Heine R.T, (2024). “Low dose versus standard dose pembrolizumab for treatment of stage IV stage non-small cell lung carcinoma: Results of the pre-planned interim analysis of the NVALT-30 clinical trial.” Presented at ESMO 2024 (Abstract 1258MO).
