For patients with an anaplastic lymphoma kinase rearrangement, a performance status (PS) of 0-2, and previously untreated NSCLC, clinicians should offer alectinib...

Non-Small Cell Lung Cancer….ALK REARRANGEMENT POSITIVE….SUBSEQUENT THERAPY...Continue alectinib or brigatinib or ceritinib or lorlatinib.

First-line treatment of ALK-rearranged NSCLC…In patients with CNS involvement, front-line use of ALK TKIs is effective, and alectinib [III, A], brigatinib [III, B] or ceritinib [IV, B] are recommended.

...- ALK-rearrangement confirmed by the Food and Drug Administration (FDA) approved test...

...- Documented ALK rearrangement based on Food and Drug Administration (FDA)-approved test...

...- Having contributive biopsy performed on fresh tissue (FFPE blocks required) taken after progression on previous therapy showing presence of anaplastic lymphoma kinase (ALK) rearrangement, assessed by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH)...

...- Phase 1: Subjects must have a histologically or cytologically confirmed diagnosis of metastatic (AJCC Stage IV) NSCLC that carries an ALK rearrangement with CNS metastases, as determined by FISH, RT-PCR, immunohistochemistry (IHC), or NGS via a CLIA-certified LDT....

...ALK-rearrangement 3....

...Confirmation of positive ALK rearrangement per local standard of care testing....

...- Documented ALK rearrangement based on an EMA approved test...

...Documented ALK rearrangement based on an EMA approved test6. ...

...- Documented ALK rearrangement as assessed by approved fluorescence in situ hybridization (FISH) test, using the Vysis ALK Break Apart FISH Probe Kit or the Ventana immunohistochemistry (IHC) test...

The ORR was 91.9% with alectinib and 92.2% for brigatinib (p-value: 0.54, 95% CI: 0.35–7.30); the intracranial ORR rates were 94.6% and 100%, respectively….Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

At the data cutoff point, the median follow-up duration was 16.5 months (95% CI; 14.7-18.3) in the brigatinib group and 27.5 months (95% CI; 24.6-30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively....Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

Our study demonstrated that alectinib was an effective and tolerable inhibitor in ALK-rearranged NSCLC patients.

Two out of three patients with metastatic ALK-rearranged LCNEC received up-front treatment with the ALK TKI alectinib and showed rapid tumor response at all metastatic sites, including multiple brain metastases.

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).

Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC….Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS....According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively.

NSCLCBM patients between 2010 and 2019 were evaluated....16 ALK positive patients received first-generation ALK inhibitor (crizotinib)...17 patients received second-generation (alectinib, ceritinib, brigatinib) and third-generation ALK inhibitors (lorlatinib)...The 5-year OS rate was 49% (95% confidence interval (CI) = 24%, 71%) for first-generation ALK inhibitors and 76% (95% CI = 40%, 92%) for second and third-generation ALK inhibitors (p-value (p) = 0.019).

...Pts with ALK+ advanced or metastatic NSCLC...In the ITT population, the median PFS was 14.4 months (9.2-NR). The OS rate at 12 months was 87.1% (71.6-94.4)...In the mITT population, ORR was 51% (CI95%:34.8-67.6) and only 2 pts experienced a PD. The disease control rate was 94.9% (CI95%:82.7-99.4).

...patients diagnosed with ALK rearranged NSCLC between 2010 to 2018 were identified...10 patients subsequently received alectinib as second line therapy, ORR 80%, mPFS 7.5 months (range 6-18).

Alectinib showed a pronounced survival benefit for patients with ALK rearrangement-positive NSCLC...

Alectinib was well tolerated, with promising antitumour activity in patients with ALK-rearranged NSCLC resistant to crizotinib, including those with CNS metastases.

A 56-year-old female and a 59-year-old male diagnosed with NSCLC exhibiting ALK gene rearrangements were treated by alectinib administration. The former had a complete response of widespread metastatic disease within 3 months, and the latter also had a substantial response.

A 32-years-old female patient...confirmed a pulmonary adenocarcinoma and an ALK rearrangement was detected...she started on alectinib. In few weeks later, she completely recovered from her respiratory symptoms and no liver function alteration recurred. The patient is still under alectinib therapy with excellent tolerability and no adverse effects.

In subcutaneous tumor models, combination of ixazomib and alectinib prominently induced tumor regression and apoptosis even though the tumors were generated from ALK-rearranged NSCLC cells with non-functional p53.