First-line treatment with lorlatinib significantly improves progression-free survival, relative to crizotinib, in patients with advanced ALK- positive, non-small-cell lung cancer, results of the phase 3 CROWN study show.

Benjamin Solomon highlights the key messages of the CROWN study of lorlatinib in advanced, ALK-positive non-small-cell lung cancer and makes the case for using the agent upfront in these patients.

The multikinase inhibitor crizotinib elicits responses and is well tolerated in people with non-small-cell lung cancer positive for MET exon 14 mutations, shows the PROFILE 1001 trial.

Crizotinib provides durable clinical benefit to patients with ROS1 -rearranged advanced non-small-cell lung cancer, show updated PROFILE 1001 data.

Treatment with brigatinib is associated with better outcomes than crizotinib in patients with anaplastic lymphoma kinase translocation-positive advanced non-small-cell lung cancer who have not received prior ALK-targeted therapy, indicate phase III trial results.

Pediatric patients with anaplastic large cell lymphomas and inflammatory myofibroblastic tumors respond well to crizotinib therapy, with more than 80% experiencing an objective response, US researchers report.

Among Japanese patients with advanced non-small-cell lung cancer harboring anaplastic lymphoma kinase translocations, progression-free survival is significantly longer with alectinib than crizotinib, shows a head-to-head phase III trial.

Following on from the initial trial results  showing a progression-free survival (PFS) advantage with lorlatinib versus crizotinib, the current unplanned analysis found that median PFS had not yet been reached in the lorlatinib-treated patients at 3 years after follow-up and was significantly longer than the 9.3 months achieved by patients given crizotinib (hazard ratio [HR]=0.27).

Session discussant Lorenza Landi (‘Regina Elena’ National Cancer Institute, Rome, Italy) said that the exploratory analysis for the efficacy of first-line entrectinib was “very new” because earlier trials in the ROS1 fusion-positive setting of crizotinib, ceritinib, and lorlatinib were all conducted in patients who had previously received chemotherapy.

The remaining 147 patients received crizotinib, including 40 (27%) people with brain metastases at baseline.

For ROS1, the first-line treatment is usually based on crizotinib and the second line on lorlatinib or on entrectinib.

Results Among 584 reported psychiatric AEs, 95 cases were selected as potentially treatment related, with higher reporting frequency for lorlatinib (26, 2.8%), followed by brigatinib (10, 1.2%), alectinib (18, 0.7%), ceritinib (12, 0.6%), and crizotinib (29, 0.3%).

Of these, 28 had previously received crizotinib as the only ALK inhibitor (group A), while the remaining 74 had received one or more second-generation ALK inhibitors (group B).

Previously lorlatinib could only be given to patients who had either received alectinib or ceritinib as their first ALK–TKI, or crizotinib and at least one other ALK–TKI.

The compounds in question were the mTOR/PI3K inhibitors everolimus, temsirolimus, and alpelisib, the antimetabolites gemcitabine and decitabine, the mitotic inhibitor cabazitaxel, and the kinase inhibitors crizotinib and dasatinib.

By contrast, the avelumab–crizotinib combination was not well tolerated by patients with ALK -negative NSCLC who had received at least one prior systemic therapy, with dose-limiting toxicities occurring in 41.7%.

Sumanta Pal provides an overview of the phase 2 SWOG 1500 study pitting the MET inhibitors cabozantinib, crizotinib, and savolitinib against sunitinib for the treatment of metastatic papillary renal cell carcinoma.

However, the prespecified futility analysis after 15 PFS events in each experimental arm and 20 events in the sunitinib arm led to closure of the crizotinib and savolitinib arms, Pal said.