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

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

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

...- 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....

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.

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).

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.

...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.

...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.

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...