KEY TAKEAWAYS
- The EORTC phase 2 study aimed to assess the safety and efficacy of nintedanib in pts with advanced thyroid cancers, such as RAIR DTC and MTC.
- The primary endpoint of the study was to evaluate PFS.
- Researchers did not find a significant improvement with nintedanib over PBO in RAIR DTC and MTC.
In patients (pts) advanced thyroid cancers like radioiodine refractory differentiated thyroid cancer (RAIR DTC) and medullary thyroid cancer (MTC), nintedanib which is a triple-angiokinase inhibitor, might serve as a potentially active treatment option.
Sophie Leboulleux and the team aimed to investigate the safety and efficacy of nintedanib, a triple-angiokinase inhibitor, in pts with advanced thyroid cancers, especially pts with RAIR DTC and MTC.
Researchers designed a double-blinded randomized (in a ratio 2:1) placebo (PBO)-controlled phase 2, multi-cohort study to investigate the safety and efficacy of nintedanib in pts with progressive, locally advanced, and/or metastatic RAIR DTC and MTC.
The primary endpoint during the study for both cohorts was the evaluation of progression-free survival (PFS) in the per-protocol (PP) population, while the secondary outcomes of the study were considered to be overall survival (OS), response rate, duration of response, and drug safety.
Results revealed that in the RAIR DTC pts-cohort, 70 out of the 75 planned pts with RAIR DTC (median age, 66 years; 39 women) with disease progression post 1 (76%) or 2 lines (24%) of prior systemic therapies were randomized administered with either nintedanib (N = 45) or PBO (N = 25). Of these, 69 pts started treatment, and 56 met all inclusion criteria (PP). At the data cutoff, the median duration of follow-up was 26.3 months in the nintedanib arm and 19.8 months in the PBO arm.
In the PP population, the median PFS was 3.7 months [80% confidence interval (CI), 1.9-6.5] in the nintedanib arm and 2.9 months (80% CI, 2.0-5.6) in the PBO arm (HR = 0.65; 80% CI, 0.42-0.99; 1-sided log-rank test P= 0.0947). No objective response was observed. The median OS was 29.6 months [80% CI, 15.2-not reached (NR)] in the nintedanib arm and not reached in the PBO arm. Grade 3-4 adverse events (AEs) of any attribution occurred in 50% of pts receiving nintedanib and in 36% of pts receiving PBO.
Conversely, in the MTC cohort, 31 out of the 67 planned pts with MTC (median age, 57 years; 8 women) with disease progression after 1 (68%) or 2 (32%) lines of previous systemic therapy were randomized to administer either nintedanib (N = 22) or PBO (N = 9). Of these, 20 pts (15 in the nintedanib arm and 5 in the PBO arm) began treatment and met all the inclusion criteria (PP).
The median PFS was 7.0 months (80% CI, 1.9-8.7) in the nintedanib arm and 3.9 months (80% CI, 3.0-5.5) in the PBO arm (HR = 0.49; 95% CI, 0.16-1.53). No objective response (OR) was recorded during the study. The median OS was 16.4 months (80% CI, 12.1-24.9) in the nintedanib arm and 12.3 months (80% CI, 7.1-NR) in the PBO arm. Grade 3-4 AEs of any attribution during the blinded period occurred in 59.1% of pts being administered with nintedanib and in 33.3% of pts with PBO.
The study concluded that nintedanib is not clinically significant, corresponding to an improvement of PFS over PBO in pts with pretreated RAIR DTC and MTC.
This work was supported by Boehringer Ingelheim France through an educational grant.
The trial was sponsored by EORTC.
Source: https://pubmed.ncbi.nlm.nih.gov/39015176/
Clinical Trial: https://clinicaltrials.gov/study/NCT01788982
Leboulleux S, Kapiteijn E, Litière S, et al. (2024). “Safety and efficacy of nintedanib as second-line therapy for patients with differentiated or medullary thyroid cancer progressing after first-line therapy. A randomized phase II study of the EORTC Endocrine Task Force (protocol 1209-EnTF).” Front Endocrinol (Lausanne). 2024 Jun 27;15:1403687. doi: 10.3389/fendo.2024.1403687. PMID: 39015176; PMCID: PMC11250516.
