Entrectinib

The safety and clinical activity of entrectinib in ROS1 fusion–positive metastatic NSCLC was determined by integrated analysis of three multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[74] Entrectinib was given orally at a dose of at least 600 mg once daily. Primary end points were objective response rate and the DOR determined by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Evaluation of tumor samples for the ROS1 gene fusion was conducted prospectively in local laboratories using either a FISH or next-generation sequencing (NGS) laboratory-developed test. Seventeen (32%) patients had received no previous systemic therapy, 23 (43%) had received one previous therapy, and 13 (25%) had received two or more lines of treatment. CNS disease was present in 23 (43%) patients at baseline. Thirty-one (59%) patients were never-smokers and 52 (98%) patients had adenocarcinoma histology.

The safety and clinical activity of entrectinib in ROS1 fusion–positive metastatic NSCLC was determined by integrated analysis of three multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[74] Entrectinib was given orally at a dose of at least 600 mg once daily. Primary end points were objective response rate and the DOR determined by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Evaluation of tumor samples for the ROS1 gene fusion was conducted prospectively in local laboratories using either a FISH or next-generation sequencing (NGS) laboratory-developed test. Seventeen (32%) patients had received no previous systemic therapy, 23 (43%) had received one previous therapy, and 13 (25%) had received two or more lines of treatment. CNS disease was present in 23 (43%) patients at baseline. Thirty-one (59%) patients were never-smokers and 52 (98%) patients had adenocarcinoma histology.

The objective response rate in 53 efficacy-evaluable patients was 77% (95% CI, 64%−88%). Six percent of patients had a complete response and 72% had a partial response. Among patients with CNS disease at baseline, the objective response rate was 74% (95% CI, 52%−90%) and all patients had a partial response. Among patients without CNS disease at baseline, the overall response rate was 80% (95% CI, 61%−92%) (10% had a complete response and 70% had a partial response).[74][Level of evidence C3]

The safety and clinical activity of entrectinib in ROS1 fusion–positive metastatic NSCLC was determined by integrated analysis of three multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[74] Entrectinib was given orally at a dose of at least 600 mg once daily. Primary end points were objective response rate and the DOR determined by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Evaluation of tumor samples for the ROS1 gene fusion was conducted prospectively in local laboratories using either a FISH or next-generation sequencing (NGS) laboratory-developed test. Seventeen (32%) patients had received no previous systemic therapy, 23 (43%) had received one previous therapy, and 13 (25%) had received two or more lines of treatment. CNS disease was present in 23 (43%) patients at baseline. Thirty-one (59%) patients were never-smokers and 52 (98%) patients had adenocarcinoma histology.

The median DOR was 24.6 months (95% CI, 11.4−34.8) in efficacy-evaluable patients; 12.6 months (95% CI, 6.5−NE) in patients with baseline CNS disease, and 24.6 months (95% CI, 11.4−34.8) in those without CNS disease at baseline.

The safety and clinical activity of entrectinib in ROS1 fusion–positive metastatic NSCLC was determined by integrated analysis of three multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[74] Entrectinib was given orally at a dose of at least 600 mg once daily. Primary end points were objective response rate and the DOR determined by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Evaluation of tumor samples for the ROS1 gene fusion was conducted prospectively in local laboratories using either a FISH or next-generation sequencing (NGS) laboratory-developed test. Seventeen (32%) patients had received no previous systemic therapy, 23 (43%) had received one previous therapy, and 13 (25%) had received two or more lines of treatment. CNS disease was present in 23 (43%) patients at baseline. Thirty-one (59%) patients were never-smokers and 52 (98%) patients had adenocarcinoma histology.

Treatment-related adverse events were assessed in 134 patients in the safety-evaluable population. Grade 1 or 2 treatment-related adverse events were observed in 79 patients (59%). Grade 3 or 4 treatment-related adverse events were observed in 46 patients (34%). Fifteen patients (11%) had serious treatment-related adverse events. There were no treatment-related deaths.

The safety and clinical activity of entrectinib in ROS1 fusion–positive metastatic NSCLC was determined by integrated analysis of three multicenter, single-arm, open-label clinical trials (ALKA-372-001/EudraCT, 2012-000148-88, STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]).[74] Entrectinib was given orally at a dose of at least 600 mg once daily. Primary end points were objective response rate and the DOR determined by blinded independent central review. Of note, time-to-event end points are difficult to interpret in the absence of a control arm. Evaluation of tumor samples for the ROS1 gene fusion was conducted prospectively in local laboratories using either a FISH or next-generation sequencing (NGS) laboratory-developed test. Seventeen (32%) patients had received no previous systemic therapy, 23 (43%) had received one previous therapy, and 13 (25%) had received two or more lines of treatment. CNS disease was present in 23 (43%) patients at baseline. Thirty-one (59%) patients were never-smokers and 52 (98%) patients had adenocarcinoma histology.

The median PFS was 19 months (95% CI, 12.2−36.6) in efficacy-evaluable patients; 13.6 months (95% CI, 4.5−NE) in patients with baseline CNS disease, and 26.3 months (95% CI, 15.7−36.6) in patients with no baseline CNS disease.