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Population-Adjusted Indirect Treatment Comparisons of Repotrectinib Among Patients with ROS1+ NSCLC
Jürgen Wolf1, Sarah Goring2, Adam Lee3
1Center for Integrated Oncology, University Hospital of Cologne, 50937 Cologne, Germany.
Background:
Head-to-head evidence comparing repotrectinib against other approved ROS1 tyrosine kinase inhibitors (TKIs) is not currently available. The objective of this study was to indirectly compare progression-free survival (PFS), the objective response rate (ORR), and the duration of response (DoR) for repotrectinib vs. crizotinib and vs. entrectinib in patients with TKI-naïve ROS1+ locally advanced or metastatic non-small-cell lung cancer (aNSCLC).
Methods:
Using evidence from a systematic literature review, unanchored matching-adjusted indirect comparisons (MAICs) were used to estimate population-adjusted hazard ratios (HRs) for PFS and DoR and odds ratios (ORs) for ORR for repotrectinib vs. crizotinib and vs. entrectinib among patients with TKI-naïve aNSCLC. The MAICs were adjusted for imbalances in baseline patient characteristics that were pre-specified as being prognostic or predictive of treatment effects. Weighted Cox (for PFS and DoR) and logistic (for ORR) regression models were fit. Supplementary analyses (SAs) explored the impact of missing data and modeling assumptions on effect estimates.
Results:
The evidence base was formed by TRIDENT-1 EXP-1 (repotrectinib; N = 71), a pooled set of five trials involving crizotinib (N = 273), and the pooled ALKA-372-001/STARTRK-1 and -2 trials (entrectinib; N = 168). After population adjustment, repotrectinib was associated with statistically significant improvements in PFS relative to crizotinib (HR = 0.44; 95% confidence interval [CI]: 0.29, 0.67) and entrectinib (HR = 0.57; 95% CI: 0.36, 0.91). Differences in ORR and DoR were not statistically significant but numerically favored repotrectinib. SAs were consistent with the main analyses across all comparisons.
Conclusions:
The analysis demonstrated the strong benefits of repotrectinib in PFS, which was robust across different SAs and supported by numerically favorable results for DoR (where available) and ORR. These results, alongside the published TRIDENT-1 clinical data, further support repotrectinib as a potential new standard of care for TKI-naïve patients with ROS1+ aNSCLC.
Insights
Repotrectinib shows significant progression-free survival benefits for ROS1+ non-small cell lung cancer patients compared to crizotinib and entrectinib. These findings support repotrectinib as a potential new standard of care.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Direct head-to-head trials comparing repotrectinib with other ROS1 tyrosine kinase inhibitors (TKIs) are lacking.
- This study addresses the need for comparative data in TKI-naïve ROS1+ advanced non-small cell lung cancer (aNSCLC).
Purpose of the Study:
- To indirectly compare progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR) for repotrectinib versus crizotinib and entrectinib.
- To evaluate repotrectinib's efficacy in TKI-naïve patients with ROS1+ aNSCLC using indirect treatment comparisons.
Main Methods:
- Systematic literature review and unanchored matching-adjusted indirect comparisons (MAICs).
- MAICs adjusted for prognostic baseline patient characteristics.
- Weighted Cox and logistic regression models were used for PFS, DoR, and ORR estimation.
Main Results:
- Repotrectinib demonstrated statistically significant improvements in PFS compared to crizotinib (HR=0.44) and entrectinib (HR=0.57).
- ORR and DoR numerically favored repotrectinib but were not statistically significant.
- Supplementary analyses confirmed the robustness of the main findings.
Conclusions:
- Repotrectinib offers significant benefits in PFS for TKI-naïve ROS1+ aNSCLC patients.
- Results support repotrectinib as a potential new standard of care.
- The findings are based on robust indirect treatment comparisons and support clinical data.
