alectinib
Sources réglementaires consultées
Indications approuvées
- Adultes atteints de CBNPC ALK positif confirmé par test : traitement adjuvant après résection si la tumeur mesure ≥4 cm ou si ganglions positifs, et maladie métastatique.
Contre-indications
Absolues
- CIMA : hypersensibilité à la substance active ou aux excipients ; l’étiquette FDA n’établit aucune contre-indication formelle.
Mises en garde cliniques
- Surveiller la fonction hépatique toutes les 2 semaines pendant 3 mois puis mensuellement. Arrêter en cas de PID/pneumopathie confirmée liée au traitement. Atteinte rénale grade 3 : suspendre jusqu’à ≤grade 1 puis reprendre à dose réduite ; grade 4 : arrêter. — OpenFDA, set_id 42c49deb-713b-427a-9670-08af08adcffb
- Contrôler CPK toutes les 2 semaines pendant le premier mois et en cas de symptômes musculaires. En cas d’anémie hémolytique, suspendre puis arrêter si confirmée. Utiliser photoprotection SPF ≥50 pendant et 7 jours après. — OpenFDA, set_id 42c49deb-713b-427a-9670-08af08adcffb
- En cas de bradycardie symptomatique, suspendre, revoir les médicaments concomitants et reprendre à dose réduite ou arrêter selon gravité et récidive. — OpenFDA, set_id 42c49deb-713b-427a-9670-08af08adcffb
Effets indésirables
Communs (≥1%)
hépatotoxicité · constipation · fatigue · myalgie · œdème · éruption cutanée · toux
Grossesse et allaitement
Les femmes doivent utiliser une contraception pendant et 5 semaines après ; les hommes pendant et 3 mois après. Ne pas allaiter pendant ni 1 semaine après.
Bibliographie récente (PubMed)
Lung cancer remains the leading cause of cancer-related mortality worldwide. Since 2024, the non-small-cell lung cancer (NSCLC) landscape has undergone a transformative shift, driven by 11 FDA approvals. Recent advances in molecular profiling, targeted therapies, and immunotherapies have revolutionized NSCLC management, ushering in an era of personalized treatment with improved patient outcomes. The increased adoption of low-dose computed tomography (LDCT) for screening has enhanced early detection, enabling intervention at more curable stages. Molecular diagnostics now play a pivotal role in guiding treatment strategies, with actionable genomic alterations (AGAs) informing the use of EGFR, ALK, ROS1, KRAS, NRG1, and other targeted inhibitors in both early and advanced settings. For instance, targeted therapies are increasingly being integrated into early-stage management, with adjuvant osimertinib for EGFR-mutated NSCLC and alectinib for ALK-positive NSCLC demonstrating substantial survival benefits. Immunotherapy, particularly immune checkpoint inhibitors, has become a cornerstone of treatment for AGA-negative NSCLC, either as monotherapy or in combination with chemotherapy, and is increasingly being utilized in the perioperative setting. Furthermore, emerging therapies such as bispecific antibodies, antibody-drug conjugates (ADCs), and novel immunotherapeutic agents show promise in addressing resistance mechanisms and improving outcomes in advanced-stage disease. Although new challenges arise, the evolving NSCLC treatment paradigm continues to prioritize precision medicine, offering hope for prolonged survival and enhanced quality of life for patients.
Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, ALK-positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking. We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, ALK-positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles. The primary end point was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat population. Other end points included central nervous system (CNS) disease-free survival, overall survival, and safety. In total, 257 patients were randomly assigned to receive alectinib (130 patients) or chemotherapy (127 patients). The percentage of patients alive and disease-free at 2 years was 93.8% in the alectinib group and 63.0% in the chemotherapy group among patients with stage II or IIIA disease (hazard ratio for disease recurrence or death, 0.24; 95% confidence interval [CI], 0.13 to 0.45; P<0.001) and 93.6% and 63.7%, respectively, in the intention-to-treat population (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Alectinib was associated with a clinically meaningful benefit with respect to CNS disease-free survival as compared with chemotherapy (hazard ratio for CNS disease recurrence or death, 0.22; 95% CI, 0.08 to 0.58). Data for overall survival were immature. No unexpected safety findings were observed. Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free s
ALEX, a global, randomized, phase III trial evaluated alectinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). This final analysis provides mature overall survival (OS), duration of response (DOR) and long-term safety data. Treatment-naïve patients with stage III/IV ALK-positive NSCLC were randomly assigned to receive alectinib [600 mg twice daily (b.i.d.)] or crizotinib (250 mg b.i.d.) until disease progression, unacceptable toxicity, withdrawal, or death. Primary endpoint was investigator-assessed progression-free survival (previously reported). Key secondary endpoints included OS, DOR and safety. A total of 303 patients (alectinib, n = 152; crizotinib, n = 151) were enrolled. At the updated data cut-off (28 April 2025), after a median follow-up of 53.5 (alectinib) and 23.3 (crizotinib) months, median OS was 81.1 [95% confidence interval (CI) 62.3 months-not estimable] versus 54.2 (95% CI 34.6-75.6 months) months, respectively [hazard ratio (HR) 0.78; 95% CI 0.56-1.08]. Improvement in median OS was observed with alectinib in patients with and without central nervous system (CNS) metastases at baseline [with CNS metastases: 63.4 (n = 59) versus 30.9 (n = 53) months with alectinib versus crizotinib, respectively (HR 0.68; 95% CI 0.40-1.15); without CNS metastases: 94.0 (n = 93) versus 69.8 (n = 98) months (HR 0.87; 95% CI 0.58-1.32)]. Median DOR in confirmed responders was longer with alectinib (42.3 months, 95% CI 31.3-51.3 months) versus crizotinib [11.1 months, 95% CI 7.9-13.0 months (HR 0.41; 95% CI 0.30-0.56)]. Long-term safety (median duration of alectinib treatment, 28.1 months) remained consistent with earlier reports, with no new or unexpected safety concerns identified. These final OS data show the sustained long-term systemic and intracranial efficacy of alectinib in the first-line treatment of ALK-positive NSCLC and confirm alectinib as a standard of care in this setting.
Next-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) (alectinib, brigatinib, and lorlatinib) demonstrate superior progression-free survival (PFS) over chemotherapy or crizotinib as first-line (1L) treatment of ALK-positive advanced non-smallcell lung cancer (NSCLC). We conducted network meta-analyses (NMAs) comparing the relative efficacy of lorlatinib with other ALK TKIs in this indication. Evidence identified from a systematic literature review and subsequent updates formed the basis of our evidence. The primary analysis investigated PFS by independent review committee (IRC) in the intent-to-treat (ITT) population. Secondary outcomes included PFS among subgroups, intracranial time to progression (IC TTP), adverse events, and discontinuation due to adverse events. For each of the outcomes, Bayesian proportional hazards NMAs estimated the relative treatment effects. Additionally, we compared the design and results of eight published NMAs conducted for 1L ALK + advanced NSCLC to date. We formed a network of 10 trials, allowing indirect treatment comparisons. Two trials directly compared alectinib (600 mg twice daily) to crizotinib and one trial directly compared lorlatinib to crizotinib. The results of the NMA show that the hazard ratios (95 % credible interval [CrI]) for ITT PFS IRC were 0.61 (95 % CrI: 0.39, 0.97) when comparing lorlatinib with alectinib (600 mg twice daily) and 0.57 (95 % CrI: 0.35, 0.93) when comparing lorlatinib with brigatinib. In the review of published NMAs, HRs for lorlatinib versus alectinib (600 mg twice daily) and brigatinib were compared. This comparison confirmed that each published NMA yielded similar results. Our NMA analysis adds to existing findings and supplements data gaps from other published NMAs. Findings from eight published NMAs consistently supported lorlatinib as a clinically effective 1L treatment for ALK + advanced NSCLC patients compared to other TKIs. No information is available on the clin