Table 2.
Key favourable and unfavourable effects of entrectinib for patients with ROS1-positive NSCLC or NTRK-positive solid tumours (pooled analysis, COD: 31 October 2018)
| Effect | Unit | Result | Uncertainties/strength of evidence |
|---|---|---|---|
| Favourable effects | |||
| Indication: patients with ROS1-positive, advanced NSCLC (n = 161) (COD: 1 May 2019) | |||
| ORR by BICR | % 95% CI | 67.1% (59.25-74.27) | Post hoc definition of the SAP |
| DOR by BICR | Median (months) 95% CI | 15.7 (13.9-28.6) | Half of the patients still on treatment at the COD |
| Indication: adult and paediatric patients with NTRK fusion-positive locally advanced or metastatic solid tumours, who have progressed following prior therapies or as initial therapy when there are no acceptable standard therapies. Pooled study population (n = 74) (COD: 31 October 2018) | |||
| ORR by BICR | % 95% CI | 63.5 (51.5-74.4) | Different ORRs across tumour types. Primary CNS tumours not included. |
| DOR by BICR | Median (months) 95% CI | 12.9 (9.3-NE) | 31% of patients on treatment at the COD |
| Unfavourable effects (COD: 31 October 2018) | |||
| Safety population (n = 504) | |||
| Total AEs | % | 99 | Interpretation of safety hampered by: Single-arm study Differences across the safety subsets in exposure, dose, administration regimen, formulation, underlying malignancy, genetics and sample size Highest uncertainty in the paediatric subset. Only two grade 5 events assessed as related to entrectinib by investigator, all occurred in adults. |
| Grade ≥3 AEs | % | 61.1 | |
| SAEs | % | 39.9 | |
| AEs leading to discontinuation | % | 9.1 | |
| AEs leading to death | % | 5.6 | |
| AEs by SOC | % | ||
| Nervous system | 82.5 | ||
| Gastrointestinal | 81.5 | ||
| General | 73.4 | ||
| Respiratory | ∼60 | ||
| Musculoskeletal | ∼55 | ||
| Grade 3-4 AEs (≥5%) | % | ||
| Anaemia | 9.7 | ||
| Weight increased | 7.3 | ||
| Dyspnoea | 5.4 | ||
| Fatigue | ∼5 | ||
| SAEs by SOC (≥5%) | % | ||
| Respiratory | 11.9 | ||
| Infections | 11 | ||
| Nervous system | 8.5 | ||
| AEs of special interest | |||
| Neurological AEs (nervous system and/or psychiatric) | % | 88.7 | |
| Renal AEs | 40.5 | ||
| Haematologic AEs | 37.1 | ||
| Eye disorders AEs | 26 | ||
| Increased weight | 26.4 | ||
| Hepatic AEs | 22.6 | ||
| Bone fractures | 6.2 | ||
| ECG QT prolonged | 4 | ||
| Congestive heart failure | 3.2 | ||
| Pneumonitis | 2 | ||
AEs, adverse events; BICR, blinded independent central review; CNS, central nervous system; COD, cut-off date; DOR, duration of response; ECG, electrocardiogram; NE, not evaluable; NSCLC, non-small-cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; ORR, objective response rate; SAEs, severe adverse events; SAP, statistical analysis plan; SOC, system organ class.