XALKORI is a kinase inhibitor indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test

Xalkori is indicated for the first-line treatment of adults with anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC).

…the NCCN NSCLC Panel preference stratified the first-line therapy regimens and decided that crizotinib is useful in certain circumstances for patients with ALK-positive metastatic NSCLC.

Pfizer Inc. (NYSE:PFE) announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for XALKORI (crizotinib) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with MET exon 14 alterations with disease progression on or after platinum-based chemotherapy. The FDA also granted Breakthrough Therapy designation for XALKORI for the treatment of patients with relapsed or refractory systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive.

Intracranial efficacy of first-line crizotinib versus chemotherapy was compared prospectively in the phase III PROFILE 1014 study in ALK-positive non-small-cell lung cancer….Among patients with tBM, IC-DCR was significantly higher with crizotinib versus chemotherapy at 12 weeks (85% v 45%, respectively; P < .001) and 24 weeks (56% v 25%, respectively; P = .006). Progression-free survival was significantly longer with crizotinib versus chemotherapy in both subgroups (tBM present: HR, 0.40; P < .001; median, 9.0 v 4.0 months, respectively; BM absent: HR, 0.51; P < .001; median, 11.1 v 7.2 months, respectively) and in the intent-to-treat population (HR, 0.45; P < .001; median, 10.9 v 7.0 months, respectively).

...The pharmacoeconomic impact of using personalized medicine for the treatment of ALK+ lung cancer.

This retrospective study examined data of patients with ALK-positive NSCLC from 18 major hospitals….Crizotinib was the most commonly prescribed ALK inhibitor, followed by alectinib and ceritinib....Patients who received ALK inhibitors as first-line therapy had significantly longer TOT (median of 11 months for first-generation inhibitors, not reached for second-generation inhibitors at the time of analysis) compared to chemotherapy (median of 2 months; P<0.01)....Patients on ALK inhibitors had longer median OS and significantly longer TOT compared to chemotherapy, suggesting long-term benefit.

In the crizotinib effectiveness and safety study, 91 patients (42 prospective, 49 retrospective) with ALK-positive NSCLC (43.9 % in first-line, 56.1 % in second or more lines) were included. The ORR was 59.3 % and the median duration of response was 13.5 months (IQR, 5.3-26.2). The median PFS was 15.8 months (95 % CI, 11.8-22.3) and the median OS was 46.5 months, with 53 patients (58.2 %) still alive at data cut-off date....This analysis of the real-world clinical experience in Spain confirms the therapeutic benefit and safety of crizotinib in advanced/metastatic ALK-positive NSCLC.

Data of patients diagnosed with advanced ALK+ NSCLC treated with first-line crizotinib sequential therapy followed by alectinib (no intermittent systemic therapy was allowed between the two ALK-TKIs) were collected in six hospitals in China....Efficacy during treatment with crizotinib...Overall response rate (ORR) was 60% (1CR + 35PR) in these patients (Table 4) as 85.7% (1CR + 35PR) of patients with target lesions demonstrated a radiological response. Median maximum tumor shrinkage rate was 56% (range −40%, 100%) (Figure 1a) in patients with measurable lesions and over half had tumor reduction over 50% (Figure 1b). As for patients with CNS metastases, intracranial ORR was 22.2% (2PR), whereas 40% of patients (2PR) with measurable CNS lesions were found to have an intracranial response (Table 4)....Sequential therapy with first-line crizotinib followed by alectinib demonstrated long-term benefits.

We investigated 60 cases of patients with ALK-positive advanced or metastatic non-small cell lung cancer (NSCLC).…Of these, 37 cases were ALK-positive with EML4 (echinoderm microtubule associated protein like 4)-ALK high percentage of positivity group. These cases benefited more from crizotinib treatment in the ORR (p = 0.046) and achieved a longer PFS (p = 0.036) compared to those with EML4-ALK low percentage of positivity group.

73 patients were included: 51 patients ALK+, 22 patients ROS1+....Objective Response Rate for ALK+ and ROS1+ was 62.7% and 55% respectively. Median progression-free survival (IC95) was ALK+ 9.4 months (7-16.1) and ROS1+ 6.6 months (4.3-14.3) median Overall Survival (IC95)....Crizotinib was effective in both ALK+ and ROS1+ aNSCLC in a real-life setting with no new safety concerns.

CONTRADICTING EVIDENCE: Medical records of patients with advanced ALK+ NSCLC treated with sequential therapy of first-line CRZ followed by ALEC (no intermittent systemic therapy was allowed between these two ALK-TKIs) from 4 hospitals in China were collected….Median PFS during the period of ALEC treatment for overall cohort and CRZ-resistant patients was 15.3 months and 13.4 months respectively....Sequential therapy of first-line CRZ followed by ALEC yielded survival benefits for patients resistant to or intolerant of CRZ.

We evaluated the data of ALK-positive metastatic NSCLC patients...Patients had received alectinib (53%), crizotinib (44.1%), and ceritinib (2.9%) as ALK inhibitor. The response ratio (complete and partial) was 66.2%.

Median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for first- and second-line ALK TKI therapy and was even shorter in patients with brain metastasis, highlighting the need for more effective treatments in this patient population.

Of the 87 ALK-positive-patients, 47 patients were treated with oral administration of crizotinib. The objective response rate (ORR) was 61.7%, the disease control rate (DCR) was 93.6%, and the mPFS was 19 months.

A single-center, retrospective study of 201 ALK-positive advanced NSCLC patients was conducted to analyze the PFS, overall survival (OS), and treatment duration (TD) of crizotinib….The median PFS1 and PFS2 were 13.2 months and 10.5 months, respectively....Crizotinib showed good efficacy in patients with ALK-positive advanced NSCLC.

Twenty-four pts with stage III-IV ALK+ NSCLC received crizotinib either as first or second-line treatment. Median duration of therapy was 11.1 mos (range 1-40.3 mos) and median PFS was 13.6 mos at data cut-off. The median PFS in LR, R and NR was 32.6 vs. 11.7 vs. 1.6 mos, respectively...

Crizotinib…was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%)...Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.

In the present retrospective analysis, we showed that patients with advanced ALK-positive NSCLC derived clinical benefit from continued ALK inhibition with crizotinib after RECIST-defined PD. These patients were more likely to have good PS at the time of PD, had responded to and exhibited extended TTP from initial crizotinib treatment, and had a site of PD particularly amenable to local therapy (brain).

...antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. Objective tumour responses were documented in 14 of 79 patients (nine complete responses, five partial responses); and the anti-tumour activity was enriched in patients with known activating ALK aberrations (eight of nine with anaplastic large-cell lymphoma, one of 11 with neuroblastoma, three of seven with inflammatory myofibroblastic tumour, and one of two with NSCLC).

Panel A shows the best response of patients with ALK-positive tumors who were treated with crizotinib, as compared with pretreatment baseline. 

We present a female patient with advanced ALK-positive NSCLC who was kept on crizotinib as first-line therapy and showed progression-free survival (PFS) of 48 months despite the data suggesting that the majority of patients on crizotinib show relapse within 1 year.