RESUMO
On October 15, 2021, the FDA approved atezolizumab as adjuvant therapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have programmed cell death ligand 1 (PD-L1) expression on ≥1% of tumor cells (TC), as detected by an FDA-approved test. The approval was based on results from the IMpower010 trial, in which 1,005 patients with NSCLC who had completed tumor resection and cisplatin-based adjuvant chemotherapy were randomly assigned 1:1 to receive atezolizumab for 16 cycles or best supportive care. The primary endpoint of disease-free survival (DFS) as assessed by investigator was tested hierarchically in the following analysis populations: stage II-IIIA NSCLC with PD-L1 expression on ≥1% of TCs (PD-L1 ≥ 1% TC); all randomly assigned patients with stage II-IIIA NSCLC; and the intent-to-treat population comprising all randomly assigned patients. At the prespecified interim DFS analysis, IMpower010 demonstrated a statistically significant and clinically meaningful improvement in DFS in the stage II-IIIA PD-L1 ≥ 1% TC analysis population, with an HR of 0.66 (95% confidence interval, 0.50-0.88; P = 0.004) favoring the atezolizumab arm. The safety profile of atezolizumab was generally consistent with known toxicities of anti-PD-(L) antibodies. The VENTANA PD-L1 (SP263) Assay (Ventana Medical Systems, Inc.) was contemporaneously approved as a companion diagnostic device to select patients with NSCLC who are PD-L1 ≥ 1% TC for adjuvant treatment with atezolizumab. Atezolizumab is the first immune checkpoint inhibitor approved by FDA for the adjuvant treatment of NSCLC.
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/patologia , Antineoplásicos/uso terapêutico , Platina/uso terapêutico , Antígeno B7-H1/metabolismo , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
FDA's approval of cemiplimab-rwlc on February 22, 2021, follows prior approvals of pembrolizumab and atezolizumab for similar indications as first-line treatment for patients with programmed death ligand-1 (PD-L1)-high advanced non-small cell lung cancer (NSCLC). Approvals of these anti-PD-L1 agents were supported by statistically significant and clinically meaningful improvements in overall survival (OS) in international, multicenter, active-controlled randomized trials. In KEYNOTE-024, the OS HR was 0.60 [95% confidence interval (CI), 0.41-0.89; P = 0.005] favoring pembrolizumab over platinum-doublet chemotherapy. In IMpower110, the OS HR was 0.59 (95% CI, 0.40-0.89; P = 0.0106) favoring atezolizumab over platinum-doublet chemotherapy. In Study 1624, the OS HR was 0.68 (95% CI, 0.53-0.87; P = 0.0022) favoring cemiplimab-rwlc over platinum-doublet chemotherapy. The progression-free survival (PFS) effect sizes for these anti-PD-L1 antibodies were also comparable across their respective registrational trials, and their safety profiles were consistent with the anti-PD-L1 class adverse event profile. The consistent survival benefits and manageable toxicity profiles of these single-agent anti-PD-L1 antibodies have established them as important treatment options in the PD-L1-high NSCLC treatment landscape. FDA approvals of these anti-PD-L1 antibodies, based on their favorable benefit-risk profiles, present effective chemotherapy-free therapeutic options for patients with advanced PD-L1-high NSCLC in the United States.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Platina/uso terapêutico , Estados UnidosRESUMO
The FDA approved capmatinib and tepotinib on May 6, 2020, and February 3, 2021, respectively. Capmatinib is indicated for patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors have a mutation leading to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Tepotinib is indicated for mNSCLC harboring MET exon 14 skipping alterations. The approvals were based on trials GEOMETRY mono-1 (capmatinib) and VISION (tepotinib). In GEOMETRY mono-1, overall response rate (ORR) per Blinded Independent Review Committee (BIRC) was 68% [95% confidence interval (CI), 48-84] with median duration of response (DoR) 12.6 months (95% CI, 5.5-25.3) in 28 treatment-naïve patients and 41% (95% CI: 29, 53) with median DoR 9.7 months (95% CI, 5.5-13) in 69 previously treated patients with NSCLC with mutations leading to MET exon 14 skipping. In VISION, ORR per BIRC was 43% (95% CI: 32, 56) with median DoR 10.8 months (95% CI, 6.9-not estimable) in 69 treatment-naïve patients and 43% (95% CI, 33-55) with median DoR 11.1 months (95% CI, 9.5-18.5) in 83 previously-treated patients with NSCLC harboring MET exon 14 alterations. These are the first two therapies to be FDA approved specifically for patients with metastatic NSCLC with MET exon 14 skipping.