For patients with an anaplastic lymphoma kinase rearrangement, a PS of 0-2, and previously untreated NSCLC, if alectinib, brigatinib, or lorlatinib are not available, clinicians should offer ceritinib or crizotinib.

The NCCN Panel preference stratified first-line therapy with brigatinib, ceritinib, or crizotinib for patients with ALK-rearrangement-positive metastatic NSCLC.

First-line treatment with crizotinib is a treatment option for patients with ALK-rearranged NSCLC…

Patients were eligible for inclusion in the study if they had locally advanced or metastatic non–small cell lung cancer that was positive for ALK rearrangements….Patients were randomly assigned, in a 1:1 ratio,to receive oral crizotinib (250 mg twice daily)...More patients in the crizotinib group than in the chemotherapy group continued treatment beyond RECIST-defined progression of disease (58 vs. 17), and the duration of such therapy was longer with crizotinib than with chemotherapy (median, 15.9 weeks [range, 2.9 to 73.4] vs. 6.9 weeks [range, 6.0 to 42.0]).

...- Patients must have an ALK rearrangement as defined via the MATCH Master Protocol...

...ALK rearrangement report including details of method and cutoff used for ALK testing...

...- Patient ALK gene rearrangement or ROS1 gene rearrangement...

...Documented evidence of an ALK rearrangement (by FISH, IHC, or NGS), ROS1 rearrangement (by FISH or NGS), or MET oncogene as defined by MET exon 14 skipping (NGS), MET Y1003X mutation or MET gene fusion (NGS) in NSCLC tumor specimen by a CLIA-approved laboratory....

...- Patients who will be screened for anaplastic lymphoma kinase (ALK) rearrangement...

...- ALK rearrangement detection method is NGS and Ventana...

...- Patients with tumors that harbor either EGFR sensitizing mutations or ALK rearrangement....

Of the 176 ALK-rearranged NSCLC patients, 106 patients were treated with crizotinib as the initial ALKi….The median OS (mOS) was...32.9 months (95% CI: 20.1–45.6 months) for patients treated with crizotinib as the initial ALKi, and not reached (NR) for those treated with a next-generation ALKi as the initial ALKi (see Figure 1). A significantly longer OS was observed either in patients treated with crizotinib (P<0.001)...those who received 1st-line crizotinib, the ORR and DCR was 72.9% (51/70) and 95.7% (67/70), and the median PFS was 10.2 months (95% CI: 8.5–11.9 months). The ORR of the patients who received 1st-line crizotinib was significantly higher than that of those who received other systemic therapies before crizotinib (P=0.01).

We included RCTs comparing ALK inhibitors with cytotoxic chemotherapy or another ALK inhibitor in individuals with incurable locally advanced or metastatic pathologically confirmed ALK‐rearranged NSCLC...six studies compared an ALK inhibitor (crizotinib, ceritinib, and alectinib) to chemotherapy....Treatment with ALK inhibitors resulted in a large increase in PFS compared to chemotherapy (HR 0.45, 95% CI 0.40 to 0.52, 6 RCTs, 1611 participants, high‐certainty evidence)….ALK inhibitors slightly improved OS (HR 0.84, 95% CI 0.72 to 0.97, 6 RCTs, 1611 participants, high‐certainty evidence).

The patients (pts) who ALK-positive and treated with crizotinib were retrospectively enrolled….The median PFS was 17.9 vs. 7.06 months (mo) in the pts with high ALK rearrangement than low (HR: 0.43, 95% CI 0.24-0.76, p 0.004). The median OS was also significant longer in high ALK rearrange group (44.6 mo vs. 16.8 mo; HR: 0.37, 95% Cl 0.1883-0.7315; p 0.004).

...patients diagnosed with ALK rearranged NSCLC between 2010 to 2018 were identified...16 (70%) received crizotinib as first line treatment, the objective response rate (ORR) was 75% and median progression free survival (mPFS) was 9 months (range 2-43).

Crizotinib was associated with systemic and intracranial disease control in patients with ALK-rearranged NSCLC who were ALK inhibitor naive and had brain metastases.

We present a case of a 17-year-old male with metastatic treatment-naïve ALK-positive adenocarcinoma. He was treated with crizotinib and obtained a prolonged response with PFS of 33 months….Crizotinib can be extremely effective in adolescents with treatment-naïve ALK-positive NSCLC but fail to prevent a central nervous system relapse....After ALK rearrangement identification, the patient started therapy with crizotinib 500 mg/day with a partial response achieved after 2 months involving lungs (Figure 1(B)), nodes, liver and bone lesions,- with a 33 month progression free survival (PFS). (Figure 3(B)).