osimertinib
Fuentes regulatorias consultadas
Indicaciones aprobadas
- CPNM con EGFR: adyuvancia tras resección con ex19del/L858R; estadio III irresecable sin progresión tras quimiorradiación; enfermedad avanzada/metastásica ex19del/L858R en monoterapia o con pemetrexed y platino; o T790M tras un EGFR-TKI. Confirma el biomarcador correspondiente antes de tratar.
Contraindicaciones
Absolutas
- CIMA: hipersensibilidad al principio activo o excipientes y uso concomitante de hipérico; la etiqueta FDA no establece contraindicaciones formales.
Advertencias clínicas
- Interrumpe ante sospecha de EPI. Fuera de la rama con quimiorradiación definitiva reciente basada en platino, suspende si se confirma. Tras esa quimiorradiación, en grado 1 continúa o interrumpe y reinicia según la situación clínica; en grado ≥2 suspende definitivamente. — OpenFDA, set_id 5e81b4a7-b971-45e1-9c31-29cea8c87ce7
- Con osimertinib más pemetrexed/platino, evalúa FEVI al inicio y durante el tratamiento en todos los pacientes; en monoterapia, hazlo si existen factores de riesgo cardiaco. Controla ECG y electrolitos cuando haya riesgo de QT. — OpenFDA, set_id 5e81b4a7-b971-45e1-9c31-29cea8c87ce7
- Ante sospecha de anemia aplásica, interrumpe; si se confirma, suspende definitivamente. Ante sospecha de eritema multiforme mayor, SJS o NET, interrumpe y suspende si se confirma. En vasculitis cutánea, interrumpe, evalúa afectación sistémica y dermatológica y considera suspensión si no hay otra causa. — OpenFDA, set_id 5e81b4a7-b971-45e1-9c31-29cea8c87ce7
Interacciones medicamentosas
- SeveraInductores potentes de CYP3A
Mecanismo: Reducen la exposición a osimertinib.
Recomendación: Evita; si es inevitable, aumenta a 160 mg/día y vuelve a 80 mg 3 semanas después de retirarlo.
OpenFDA, set_id 5e81b4a7-b971-45e1-9c31-29cea8c87ce7
- SeveraSustratos BCRP/P-gp o fármacos que prolongan QT
Mecanismo: Osimertinib puede aumentar la exposición a sustratos y sumar riesgo de QT.
Recomendación: Vigila toxicidad de sustratos de margen estrecho y evita fármacos QT cuando sea posible; si no, controla ECG/electrolitos.
OpenFDA, set_id 5e81b4a7-b971-45e1-9c31-29cea8c87ce7
Eventos adversos
Comunes (≥1%)
diarrea · exantema · dolor musculoesquelético · toxicidad ungueal · piel seca · estomatitis · fatiga
Embarazo y lactancia
Verifica embarazo. Las mujeres deben usar anticoncepción durante y 6 semanas después; los hombres, durante y 4 meses después. No amamantes durante ni 2 semanas después.
Bibliografía reciente (PubMed)
Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI-sensitizing and EGFR T790M resistance mutations. Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy. In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced non-small-cell lung cancer (NSCLC) who had not previously received treatment for advanced disease to receive osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg per square meter of body-surface area] plus either cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or to receive osimertinib monotherapy (80 mg once daily). The primary end point was investigator-assessed progression-free survival. Response and safety were also assessed. A total of 557 patients underwent randomization. Investigator-assessed progression-free survival was significantly longer in the osimertinib-chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; P<0.001). At 24 months, 57% (95% CI, 50 to 63) of the patients in the osimertinib-chemotherapy group and 41% (95% CI, 35 to 47) of those in the osimertinib group were alive and progression-free. Progression-free survival as assessed according to blinded independent central review was consistent with the primary analysis (hazard ratio, 0.62; 95% CI, 0.48 to 0.80). An objective (complete or partial) response was observed in 83% of the patients in the osimertinib-chemotherapy group and in 76% of those in the osimertinib group; the median response duration was 24.0 months (95% CI, 20.9 to 27.8) and 15.3 months (95% CI, 12.7 to 19.4), respectively. The incidence of grade 3 or higher adverse events from any cause was higher with the combination than with monotherapy - a finding driv
Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3%
Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55
Previous results from this phase 3 trial showed that progression-free survival among participants with previously untreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC) was significantly improved with amivantamab-lazertinib as compared with osimertinib. Results of the protocol-specified final overall survival analysis in this trial have not been reported. We randomly assigned, in a 2:2:1 ratio, participants with previously untreated EGFR-mutated (exon 19 deletion or L858R substitution), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib, osimertinib, or lazertinib. Overall survival (assessed in an analysis of the time from randomization to death from any cause) in the amivantamab-lazertinib group as compared with the osimertinib group was a key secondary end point. Additional end points included safety. A total of 429 participants each were assigned to receive amivantamab-lazertinib or osimertinib. Over a median follow-up of 37.8 months, amivantamab-lazertinib led to significantly longer overall survival than osimertinib (hazard ratio for death, 0.75; 95% confidence interval, 0.61 to 0.92; P = 0.005); 3-year overall survival was 60% and 51%, respectively. At the clinical cutoff date, 38% of participants in the amivantamab-lazertinib group and 28% in the osimertinib group were still receiving the assigned treatment. Adverse events of grade 3 or higher were more common with amivantamab-lazertinib (in 80% of participants) than with osimertinib (in 52%), particularly skin-related events, venous thromboembolism, and infusion-related events; these findings were consistent with the established safety profile of each treatment. No new safety signals were observed with additional follow-up. Amivantamab-lazertinib led to significantly longer overall survival among participants with previously untreated EGFR-mutated advanced NSCLC than osimertinib but was associated with an increased risk of adverse events of g
The primary analysis of this trial showed that first-line treatment with osimertinib plus chemotherapy with a platinum-based agent and pemetrexed led to significantly longer progression-free survival than osimertinib monotherapy among patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC). Results from the planned final analysis of overall survival are needed. In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced NSCLC who had not previously received treatment for advanced disease to receive either osimertinib (80 mg once daily) plus chemotherapy with pemetrexed (500 mg per square meter of body-surface area) and a platinum-based agent (cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or osimertinib monotherapy (80 mg once daily). The key secondary end point was overall survival. A total of 557 patients were randomly assigned to the osimertinib plus platinum-pemetrexed group (279 patients) or the osimertinib monotherapy group (278 patients). The median overall survival was 47.5 months in the osimertinib plus platinum-pemetrexed group and 37.6 months in the osimertinib monotherapy group (hazard ratio for death, 0.77; 95% confidence interval, 0.61 to 0.96; P = 0.02). Grade 3 or higher adverse events of any cause were reported in 70% of the patients in the osimertinib plus platinum-pemetrexed group and in 34% of the patients in the osimertinib monotherapy group; adverse events leading to the discontinuation of osimertinib were reported in 12% and 7%, respectively. Among patients with EGFR-mutated advanced NSCLC, first-line treatment with osimertinib plus platinum-pemetrexed led to significantly longer overall survival than osimertinib monotherapy and was associated with an increased risk of reversible adverse events of grade 3 or higher. (Funded by AstraZeneca; FLAURA2 ClinicalTrials