TABLE 3.
Study Outcomes: Entrectinib in Patients With Advanced or Metastatic NTRK Fusion-Positive Solid Tumors: Integrated Analysis of Three Phase I-II Trials
| Outcome/Timeframe | Study Results | Certainty of the Evidence (quality of the evidence) | Plain Text Summary |
|---|---|---|---|
| ORR (coprimary end point) median follow-up, 12.9 months | ORR: 31 of 54 (57%; 95% CI, 43.2% to 70.8%), 4 CR (7%), 27 PR (50%), 9 SD (17%); 2 of 3 patients with pancreatic cancer experienced PR by RECIST v1.1 (67%; 95% CI, 9% to 99%) | Moderate (1, 2) | Entrectinib may improve ORR (coprimary end point) |
| Median duration of response (coprimary end point) | By blinded independent review: 10.4 months (95% CI, 7.1 months to not estimable) | Low (1) | Entrectinib may improve duration of response (coprimary end point) |
| Median progression-free survival | Median PFS: 11.2 months (95% CI, 8.0 to 14.9 months) | Low (1) | Entrectinib may improve progression-free survival |
| Median overall survival | 21 months (95% CI, 14.9 months to not estimable) | Low (1) | Entrectinib may improve overall survival |
| Most common grade 3–4 adverse events in NTRK fusion-positive safety population | Anemia (12%), increased weight (10%), fatigue (7%) | Very low (1) | Entrectinib may worsen adverse events |
| Dose modifications | Treatment discontinuations (4%), dose interruptions (31%), dose reductions as a result of treatment-related adverse events (40%); the latter were most commonly because of anemia (7%), increased blood creatinine levels (6%), and fatigue (6%) | Very low (1) | Entrectinib may result in dose modifications, interruptions, and reductions |
NOTE. Results from Doebele et al.18 (1) Downgrade: risk of bias, population dissimilarity (locally advanced included), low number of patients (3 of 54 patients with pancreatic cancer), commercially funded. (2) Upgrade: large magnitude of effect. Population: 54 patients with NTRK fusion-positive patients with solid tumors, including 3 patients with pancreatic cancer. Intervention: entrectinib (600 mg orally daily). Comparator: no comparator.
Abbreviations: CR, complete response; ORR, objective response rate; PR, partial response; SD, stable disease.