Chugai Pharmaceutical Co., Ltd...Taiwan Food and Drug Administration (TFDA) for Chugai’s Alecensa® (alectinib) as an adjuvant treatment following tumor resection (tumors ≥ 4 cm or node positive) for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), on August 1, 2024.

...European Commission has approved a Chugai originated anaplastic lymphoma kinase (ALK) inhibitor Alecensa® (generic name : alectinib) monotherapy, as adjuvant treatment following tumour resection for adult patients with ALK-positive non-small cell lung cancer (NSCLC) at high risk of recurrence (Stage IB [tumors ≥ 4 cm]–IIIA NSCLC [7ᵗʰ edition UICC/AJCC]).

On April 18, 2024, the Food and Drug Administration approved alectinib (Alecensa, Genentech, Inc.) for adjuvant treatment following tumor resection in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test.

Roche...announced that the China National Drug Administration (CNDA) has granted marketing authorisation for Alecensa (alectinib) as a monotherapy treatment for patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC).

Alectinib (Alecensa) is accepted for use within NHS Scotland...as monotherapy for first line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).

Alecensa as monotherapy is indicated for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC)....Alecensa as monotherapy is indicated for the treatment of adult patients with ALK‑positive advanced NSCLC previously treated with crizotinib.

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

…the NCCN NSCLC Panel preference stratified the first-line therapy regimens and decided that brigatinib and ceritinib are "other recommended" options for patients with ALK-positive metastatic NSCLC; alectinib is the preferred first-line therapy option for ALK-positive metastatic NSCLC.

Alectinib is associated with longer PFS and lower toxicity than crizotinib and showed activity against CNS disease in patients previously untreated with ALK-positive NSCLC [I, A]

Hoffmann-La Roche Limited...granted approval of Alecensaro® (alectinib) monotherapy as adjuvant treatment following tumour resection for patients with stage IB (tumours ≥ 4 cm) to IIIA* anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

...US Food and Drug Administration has accepted its supplemental new drug application (sNDA) seeking approval for the ALK inhibitor Alecensa (alectinib) as adjuvant therapy for early-stage ALK-positive non-small cell lung cancer...The FDA has granted Roche's sNDA priority review and is assessing it under its Real-Time Oncology Review pilot program...

Roche...announced today that the Phase III ALINA study evaluating Alecensa® (alectinib), compared with platinum-based chemotherapy, met its primary endpoint of disease-free survival (DFS) at a prespecified interim analysis. Alecensa demonstrated a statistically significant and clinically meaningful improvement in DFS as adjuvant therapy in people with completely resected stage IB (tumour ≥4cm) to IIIA (UICC/AJCC 7th edition) anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

Pts had stage IIIB/IV ALK+ NSCLC by central IHC and ECOG PS 0–2…a durable PFS benefit was seen for ALC vs CRZ (HR 0.33, 95% CI 0.23–0.49; median PFS [INV] 41.6 vs 11.1 m) and a clinically meaningful improvement in OS (HR 0.60, 95% CI 0.37–0.99; 5-year OS rate 66.4 vs 56.0%....PFS/OS benefit of ALC occurred in pts with or without CNS mets at baseline (Table) and across pre-specified subgroups.....With ≥5 years follow-up, 1L alectinib 600mg BID continues to provide clinical benefit to Asian pts with advanced ALK+ NSCLC, with no new safety concerns.

...phase II or III randomized controlled trials (RCTs) in ALK inhibitor-naïve ALK-positive NSCLC patients...brigatinib significantly reduced the risk of disease progression or death...No significant differences were observed between brigatinib and alectinib in IRC-assessed (HR, 0.98; 95% CI, 0.61-1.57) or investigator-assessed PFS (HR, 1.01; 95% CI, 0.64-1.58) for overall patients...

ALK+ NSCLC (by IHC and FISH or RT-PCR) patients were randomized 1:1 either to receive ALC (300 mg BID, n = 103) or CRZ (250 mg BID, n = 104)....In the final PFS analysis, ALC continued to demonstrate the superiority in IRF-PFS in ALK-inhibitor naïve ALK+ NSCLC...

Roche...announced that the US Food and Drug Administration (FDA) has accepted the company’s supplemental New Drug Application (sNDA) and granted Priority Review for Alecensa (alectinib) as an initial (first-line) treatment for people with anaplastic lymphoma kinase (ALK)-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for the first-line treatment of ALK positive non-small cell lung cancer (NSCLC) to Alecensa, a highly selective ALK inhibitor created by Chugai.

ALK+ NSCLC pts were randomized 1:1 either to receive ALC (300 mg b.i.d.) or CRZ (250 mg b.i.d.)...The PFS HR of ALC arm to CRZ arm was 0.34 (99.6826% CI: 0.17-0.70, stratified log-rank p<0.0001)....At J-ALEX IA, ALC demonstrated significantly prolonged PFS compared with CRZ...

The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point.

ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients...Independent Review Committee-assessed PFS was also significantly longer with alectinib [HR 0.32 (95% CI: 0.17-0.59); median PFS was 7.1 months (95% CI: 6.3-10.8) with alectinib and 1.6 months (95% CI: 1.3-4.1) with chemotherapy]. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001).

Investigator-assessed progression-free survival was significantly prolonged with alectinib versus crizotinib (hazard ratio [HR] 0·22, 95% CI 0·13-0·38; p<0·0001; median progression-free survival not estimable vs 11·1 months)....Our results align with ALEX, confirming the clinical benefit of 600 mg of alectinib twice per day as a first-line treatment for ALK-positive non-small-cell lung cancer.

...Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test...

...Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. ALK positivity must have been determined by a validated fluorescence in situ hybridization (FISH) test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3)...

...Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test. Sufficient tumor tissue available to perform ALK IHC is required. Ventana IHC testing will be performed at the designated central laboratory...

In this preliminary analysis from NAUTIKA1, neoadjuvant alectinib demonstrated major pathological response and was well tolerated in patients with ALK+ NSCLC.

The data of 38 patients who were diagnosed with anaplastic lymphoma kinase-positive non small cell lung carcinoma in our clinic between 2016 and 2021…The progression rate was lower in alectinib than the crizotinib patients…

We sought to assess the overall treatment pattern characteristics, safety, and effectiveness outcomes of real-world patients with ALK-positive aNSCLC receiving ALK TKIs….alectinib was associated with favorable survival outcomes with longer time to adverse events (AE) requiring medical interventions, disease progression, and death, in the context of real-world use.

The aim of the present study was to investigate the efficacy and safety of ALKis in ALK-positive NSCLC….Moreover, alectinib was significantly more effective than crizotinib (1.54, 1.02 to 2.5) in achieving the best ORR.

In this retrospective study, pts were eligible if they had advanced ALK+ NSCLC with CNS relapse on standard dose alectinib (600 mg twice daily) and subsequently received dose-escalated alectinib (900 mg twice daily)....CNS disease control rate (DCR) was 92.0% (95% CI, 74.0-99.0), with median CNS duration of response (DoR) of 5.3 mos (95% CI, 3.4-8.3) and median CNS PFS of 7.1 mos (95% CI, 4.4-13.7)....Dose intensification of alectinib demonstrated meaningful efficacy and tolerability in pts with metastatic ALK+ NSCLC who had experienced CNS disease relapse on standard dose alectinib...

To compare the efficacy and safety of alectinib with other ALK inhibitors in treating patients with metastatic or locally advanced ALK-positive NSCLC....Subgroup analysis by brain metastasis at baseline showed the superiority of alectinib over crizotinib and a similar effect compared with second-and third-generation inhibitors.

Observational and descriptive study of patients with advanced NSCLC and ALK+ treated with alectinib in the period 2019-2022….The ORR was 57.2%. Complete response ocurred in 28.6% of patients. The median response to treatment was 16 months and the median PFS was 16 months.

Out of 100 ALK-positive aNSCLC patients treated with ALK TKIs, median age was 60 years and 62% were female...median Overall Survival (mOS) from start of first ALK TKI was 28 months (CI95% 18-NR). In first line, exposure to alectinib was associated with numerically higher mOS (36 months) when compared to crizotinib (18 months, HR = 0.58, CI95% 0.2-1.6).

All ALK+ advanced NSCLC pts initiating alectinib…The best response was complete (CR), partial (PR) and stable (SD) in 21%, 58% and 17%.

Adults with advanced ALK-positive NSCLC who received first-line alectinib (from December 11, 2015) or crizotinib (from January 1, 2014) were included from a real-world database…rwPFS (weighted hazard ratio [wHR] = 0.46, 95% confidence interval [CI]: 0.33-0.65) and real-world overall survival (wHR = 0.46, 95% CI: 0.31-0.69) were significantly improved with alectinib versus crizotinib....Outcomes were significantly improved with first-line alectinib versus crizotinib in patients with advanced ALK-positive NSCLC in the U.S. real-world setting.

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.

The first five patients with ALK+ NSCLC who have undergone neoadjuvant treatment and surgery were included in this analysis (data as of 22 February 2022). All patients completed at least 8 weeks of neoadjuvant treatment (median treatment duration: 8.14 weeks [range: 8.0-8.7]), had surgery during the defined protocol window (Day 57 [+10 days]), and had a complete resection (R0 resection rate: 100%) without delays or major complications....In this preliminary analysis from the ALK+ cohort of NAUTIKA1, alectinib was well tolerated in patients with ALK+ NSCLC and is considered feasible for neoadjuvant treatment.

This multicentre retrospective study was conducted to analyse the clinical characteristics, treatment approaches, associated toxicities and efficacy outcomes of alectinib in 120 patients with advanced ALK+ NSCLC...After a median duration of alectinib treatment of 9.6 months, the objective response rate (ORR) was 54.5%, disease control rate (DCR) was 80%, median progression-free survival (PFS) was 9.4 months and median overall survival (OS) was 24.1 months.

This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib….A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively.

Our results revealed alectinib had better PFS and higher intracranial efficacy compared to crizotinib in ALK-positive NSCLC…

We retrospectively analyzed the treatment history of 104 patients with ALK[+] NSCLC....In particular, the ORR of Alectinib and Brigatinib was significantly higher than that of Ceritinib and Ensartinib (P < 0.000), while the mPFS of Alectinib was significantly better than Ensartinib (P = 0.029)....For patients with CNS metastases, treatment with Alectinib and Brigatinib results in higher ORR and PFS.

Median overall progression-free survival (PFS) was 32.8 months (95% CI 24.4– 41.2 months) in patients treated with alectinib and 8.0 months (95% CI 7.3– 8.7 months) in patients treated with crizotinib….Compared with crizotinib, alectinib showed superior efficacy and lower toxicity in the treatment of ALK-positive patients with NSCLC and symptomatic and synchronic brain metastases.

Compared with crizotinib, alectinib exhibited superior efficacy in PFS (HR [hazard ratio]: 0.35, [0.25-0.49], p < 0.00001), OS (HR: 0.66, [0.47-0.92], p = 0.02)...In both antitumor efficacy and safety, alectinib appears to be superior to crizotinib for the treatment of 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 alectinib...All patients included in the study had at least one radiological evaluation, and ORR in the overall population was 47.5% (2CR + 27PR) (Table 6). A radiological response was found in 28 patients (60.9%, 1CR + 27PR) with target lesions. Median maximum tumor shrinkage rate was 39% (Figure 1c) as over 30% of patients with measurable lesions were found to have tumor reduction of over 50% (Figure 1d)....Sequential therapy with first-line crizotinib followed by alectinib demonstrated long-term benefits.

A total of 120 patients with ALK-positive NSCLC were enrolled and randomly assigned to receive crizotinib treatment (54 patients, the control group) or alectinib treatment (66 patients, the research group)….Alectinib was clinically more efficacious and safer than crizotinib for ALK-positive NSCLC treatment.

Compared with ceritinib RWD, alectinib-exposed patients had significantly longer OS in alectinib trials (adjusted hazard ratio [HR], 0.59; 95% CI, 0.44-0.75; P < .001) and alectinib RWD (HR, 0.46; 95% CI, 0.29-0.63; P < .001) after adjustment for baseline confounders....Alectinib exposure was associated with longer OS compared with ceritinib in patients with ALK-positive NSCLC...

Adult pts with advanced ALK+ NSCLC who received 1L ALC (from 11 Dec 2015) or CRZ (from 1 Jan 2014) were included...In the RWD cohort, rwPFS and rwOS were significantly improved with ALC vs CRZ (Table)....Outcomes were significantly improved with 1L ALC vs CRZ in pts with advanced ALK+ NSCLC in the real-world setting.

...mPFS2 for alectinib is 12 months (95%CI 2,3 – 21,6)….treatment with alectinib in the first line gives better survival benefit than earlier generation ALK TKIs.

This study aims to evaluate the different efficacies of alectinib and crizotinib on progression-free survival (PFS), central nervous system (CNS) progression and adverse events (AEs) in NSCLC patients with ALK-positive….Alectinib showed significant PFS superiority over crizotinib. The pooled HR =0.41 (95% CI: 0.29-0.53) indicated that the alectinib therapy group did have significantly longer PFS than that of the crizotinib group.

Studies about the efficacy of alectinib versus crizotinib in the treatment of ALK-positive non-small cell lung cancer...The results of meta-analysis showed that: the overall response rate [OR = 2.07, 95% CI (1.41, 3.06), P = 0.0002], the progression free survival [HR = 0.34, 95% CI (0.21, 0.55), P <0.0001], the partial response [OR = 1.71, 95% CI (1.19, 2.46), P = 0.003], P = 0.001], in alectinib group were higher than that of crizotinib group.

Of the 65 patients with ALK-positve NSCLC who underwent treatment failure of crizotinib, 43 (66.2%) received alectinib and 22 (33.8%) received ceritinib as the subsequent treatment….Patients receiving alectinib treatment, compared to ceritinib, showed a similar 12-month PFS rate (61.0% [95% confidence interval, 47.1 to 78.9%] vs. 54.5% [95% CI, 37.3 to 79.9%]); HR for disease progression or death, 0.61 (95% CI, 0.31–1.17; p = 0.135) and median PFS (20.1 vs. 13.9 months; log-rank test p = 0.100, Fig. 1a) than those receiving ceritinib treatment....A numerically higher response rate was noted in the patients who received alectinib treatment (73.2 vs. 50.0%, p = 0.096; Table 2).

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%.

In this retrospective study, ALK+ NSCLC patients...intracranial overall response rate(ic-ORR) was 82% (9/11), 76.5% (13/17), 43% (3/7) in each cohort….Our results indicated that Alectinib showed substantial intracranial activity in ALK-positive patients...

...patients with ALK-positive NSCLC initiating alectinib(600 mg twice daily)...The ORR was 89.7%(35/39) and 2 patients had a complete response. Among 23 patients with measurable CNS lesions at baseline, a CNS response occurred in 22 of 23 patients (95.6%);4 patients had a complete CNS response....study confirms the efficacy and safety of alectinib in real-world advanced ALK+ NSCLC...

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 the ALK- and ROS1-positive groups, respectively.

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.

Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases.

This study assessed the efficacy of alectinib in patients with ALK-positive NSCLC and analyzed the prognostic factors….the median PFS of patients undergoing second-line treatment was 15.0 months [95% confidence interval (CI): 0.00-32.23].

A 41-year-old man was pathologically diagnosed with locally advanced ALK-positive stage IIIB NSCLC. Alectinib was prescribed to induce tumor downstaging and facilitate the subsequent surgical resection. The tumor was successfully downstaged and pathological complete response was achieved.

We hereby report the case of a 90-year-old patient with anaplasic lymphoma kinase-rearranged lung cancer...alectinib was administered by percutaneous gastrostomy….Total tumor regression was 28%, 37%, and 60% compared with the first baseline CT-scan after 1, 3, and 6 months of treatment respectively...

Patient 1 was a 46-year-old woman diagnosed with non-small cell lung cancer with an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene (ALK+)….Alectinib was initiated as a second line therapy,...Good response was consequently achieved, characterized with improved overall performance and without significant adverse events.