Lorlatinib is recommended in patients with ROS1-positive metastatic NSCLC whose disease becomes resistant to crizotinib, ceritinib, or entrectinib...

...- For ROS1 positive patients: failure to prior treatment with at least crizotinib...

...All patients (ALK positive and ROS1 positive) must have archival tissue sample available and collected prior to enrollment....

...- Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (Stage IV, AJCC v7.0) that carries an ALK or ROS1 rearrangement (ROS1-positive patients will only be allowed in dose escalation) as determined using a local diagnostic test or a commercial test or by the Food and Drug Administration (FDA)-approved FISH test, using Vysis® ALK Break apart FISH Probe, or the Ventana® immunohistochemistry (IHC) test....

In contrast, in ROS1+/TP53- patients, RR was 50%, median PFS was 26.3 months (HR: 2.30, 95% CI: 0.78-6.75) and median OS was 30.7 months (HR: 2.75, 95% CI: 0.84-8.96).

We reviewed TRAEs and therapeutic efficacy for advanced non-small-cell lung cancer (NSCLC) patients receiving lorlatinib at our centre….Overall, the ORR was 53.8% and 71.4% for ALK- and ROS1- positive NSCLC, respectively….Lorlatinib is an effective treatment for ALK- and ROS1-driven NSCLC.

Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months [95% confidence interval (CI) 5.0-9.9 months] and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%....Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.

...eligible patients with ALK- or ROS1-positive advanced NSCLC...received lorlatinib 100 mg once daily...Efficacy results of the total Asian population (summarized in Table 1) were similar to the overall population; with ORR of 56% versus 47%, IC-ORR of 59% versus 63% and median PFS of 8.2 versus 7.3 months, respectively.

...efficacy and safety of lorlatinib in previously treated ALK/ROS1(+) NSCLC...ROS1 cohort...EC and IC RR were 62% and 67% with DCR of 92% and 78% respectively. Median DoT was 18.1±2.5 months and mOS of 90.3±24.4 months.

ALK-positive patients showed a response rate of 43.2%, while 85.7% percent of the ROS1-positive patients were considered responders. Median overall survival from lorlatinib initiation was 10.2 and 20.0 months for te ALK- and ROS1-positive groups, respectively. 

Lorlatinib has demonstrated clinical antitumour activity against both intracranial and extracranial lesions in patients with anaplastic lymphoma kinase- or c-ros oncogene 1 (ROS1)-positive non-small cell lung carcinoma.

Here we report the analysis of consecutive patients with advanced, refractory, ROS1+ NSCLC enrolled in the French EAP of lorlatinib...Median PFS and median overall survival from the initiation of lorlatinib were 7.6 months (95%CI, 6.18-10.05) and 20.7 months (95%CI, 12.25-27.46) respectively. Median lorlatinib duration was 7.4 months (range: [0.5-34.7]). Overall response rate (ORR) and disease control were 45.5% (95%CI, 33.4% - 57.5%) and 84.8% (95%CI, 76.2% - 93.5%) respectively. CNS ORR was 41.8% (95%CI, 30.0% - 53.6%). 44 (62%) patients experienced tumor progression....These real-life results confirmed lorlatinib as a major treatment option for patients with advanced ROS1+ NSCLC after failure of crizotinib.

ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ± 2.5 months and mOS of 90.3 ± 24.4 months.

...143 (71.5%) ALK+, 57 (28.5%) ROS1+, 87 (44%) men...At the time of initiation of lorlatinib, 146 (74%) patients had Central Nervous System (CNS) disease (78 % for ALK+, 63% for ROS1+), 131 (76%) were PS 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 3%/17%/27%/53%of ALK+ patients and in 30%/30%/16%/24%of ROS1+ patients, respectively....Median PFS and OS from the initiation of lorlatinib were 11.8 (95% CI 7.3-14.6) months and NR (95% CI 18.6-NR) months, respectively for ALK+ patients and 7.6 (95% CI 6.2-10.2) months and 20.9 (95% CI 10.0-NR) months, respectively for ROS1+ patients....These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC.

Among ALK+ patients treated with 2 prior TKIs, ≥2 prior TKIs, and ≥3 prior TKIs, objective response rate (ORR) and median progression-free survival (mPFS) were 42% (95% CI: 26-59; n = 38)...For ROS1+ patients, ORR and mPFS were 41% (95% CI: 18-67; n = 17) and 11.9 months (95% CI: 6.4-NR; n = 19)....Lorlatinib demonstrated meaningful activity in TKI-refractory ALK+ or ROS1+ NSCLC patients enrolled in early or expanded access programs.

In ROS1-positive patients, including seven crizotinib pre-treated patients, an objective response was achieved by six (50%) of 12 patients (95% CI 21–79)....In this phase 1, dose-escalation study, lorlatinib showed both systemic and intracranial activity in patients with advanced ALK-positive or ROS1-positive NSCLC...