Osimertinib plus chemotherapy

A multicenter, randomized, open-label, phase III trial (FLAURA2 [NCT04035486]) compared osimertinib plus chemotherapy with osimertinib alone in patients with advanced NSCLC and EGFR variants (EGFR exon 19 deletion or EGFR L858R variant). Patients had not previously received treatment for advanced disease. Patients received osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg/m2 of body-surface area] plus either cisplatin [75 mg/m2] or carboplatin [pharmacologically guided dose, area under the curve (AUC) = 5]) or osimertinib monotherapy (80 mg once daily). Chemotherapy in the combination arm was given for four 21-day cycles and was followed by osimertinib and pemetrexed (500 mg/m2) maintenance every 3 weeks. A total of 557 eligible patients were randomly assigned in a 1:1 ratio. The primary end point was investigator-assessed PFS.[51]Analysis of OS, a secondary end point, requires further follow-up (data maturity, 27%).

A multicenter, randomized, open-label, phase III trial (FLAURA2 [NCT04035486]) compared osimertinib plus chemotherapy with osimertinib alone in patients with advanced NSCLC and EGFR variants (EGFR exon 19 deletion or EGFR L858R variant). Patients had not previously received treatment for advanced disease. Patients received osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg/m2 of body-surface area] plus either cisplatin [75 mg/m2] or carboplatin [pharmacologically guided dose, area under the curve (AUC) = 5]) or osimertinib monotherapy (80 mg once daily). Chemotherapy in the combination arm was given for four 21-day cycles and was followed by osimertinib and pemetrexed (500 mg/m2) maintenance every 3 weeks. A total of 557 eligible patients were randomly assigned in a 1:1 ratio. The primary end point was investigator-assessed PFS.[51]Analysis of OS, a secondary end point, requires further follow-up (data maturity, 27%).

PFS was 25.5 months (24.7–not calculable) for patients in the osimertinib-plus-chemotherapy group and 16.7 months (14.1–21.3) for patients in the osimertinib-monotherapy group (HR, 0.62; 95% CI, 0.49–0.79; P < .001).[51][Level of evidence B1] PFS was assessed according to blinded independent central review and was consistent with the primary analysis (HR, 0.62; 95% CI, 0.48–0.80).

A multicenter, randomized, open-label, phase III trial (FLAURA2 [NCT04035486]) compared osimertinib plus chemotherapy with osimertinib alone in patients with advanced NSCLC and EGFR variants (EGFR exon 19 deletion or EGFR L858R variant). Patients had not previously received treatment for advanced disease. Patients received osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg/m2 of body-surface area] plus either cisplatin [75 mg/m2] or carboplatin [pharmacologically guided dose, area under the curve (AUC) = 5]) or osimertinib monotherapy (80 mg once daily). Chemotherapy in the combination arm was given for four 21-day cycles and was followed by osimertinib and pemetrexed (500 mg/m2) maintenance every 3 weeks. A total of 557 eligible patients were randomly assigned in a 1:1 ratio. The primary end point was investigator-assessed PFS.[51]Analysis of OS, a secondary end point, requires further follow-up (data maturity, 27%).

At 24 months, 57% (95% CI, 50%–63%) of the patients in the osimertinib-plus-chemotherapy group and 41% (95% CI, 35%–47%) of those in the osimertinib-alone group were alive and progression-free.

A multicenter, randomized, open-label, phase III trial (FLAURA2 [NCT04035486]) compared osimertinib plus chemotherapy with osimertinib alone in patients with advanced NSCLC and EGFR variants (EGFR exon 19 deletion or EGFR L858R variant). Patients had not previously received treatment for advanced disease. Patients received osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg/m2 of body-surface area] plus either cisplatin [75 mg/m2] or carboplatin [pharmacologically guided dose, area under the curve (AUC) = 5]) or osimertinib monotherapy (80 mg once daily). Chemotherapy in the combination arm was given for four 21-day cycles and was followed by osimertinib and pemetrexed (500 mg/m2) maintenance every 3 weeks. A total of 557 eligible patients were randomly assigned in a 1:1 ratio. The primary end point was investigator-assessed PFS.[51]Analysis of OS, a secondary end point, requires further follow-up (data maturity, 27%).

An objective response (complete or partial) occurred in 83% of patients who received osimertinib plus chemotherapy and 76% of patients who received osimertinib alone.

A multicenter, randomized, open-label, phase III trial (FLAURA2 [NCT04035486]) compared osimertinib plus chemotherapy with osimertinib alone in patients with advanced NSCLC and EGFR variants (EGFR exon 19 deletion or EGFR L858R variant). Patients had not previously received treatment for advanced disease. Patients received osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg/m2 of body-surface area] plus either cisplatin [75 mg/m2] or carboplatin [pharmacologically guided dose, area under the curve (AUC) = 5]) or osimertinib monotherapy (80 mg once daily). Chemotherapy in the combination arm was given for four 21-day cycles and was followed by osimertinib and pemetrexed (500 mg/m2) maintenance every 3 weeks. A total of 557 eligible patients were randomly assigned in a 1:1 ratio. The primary end point was investigator-assessed PFS.[51]Analysis of OS, a secondary end point, requires further follow-up (data maturity, 27%).

The median DOR was 24.0 months (95% CI, 20.9–27.8) in the osimertinib-plus-chemotherapy group and 15.3 months (95% CI, 12.7–19.4), in the osimertinib-alone group.

A multicenter, randomized, open-label, phase III trial (FLAURA2 [NCT04035486]) compared osimertinib plus chemotherapy with osimertinib alone in patients with advanced NSCLC and EGFR variants (EGFR exon 19 deletion or EGFR L858R variant). Patients had not previously received treatment for advanced disease. Patients received osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg/m2 of body-surface area] plus either cisplatin [75 mg/m2] or carboplatin [pharmacologically guided dose, area under the curve (AUC) = 5]) or osimertinib monotherapy (80 mg once daily). Chemotherapy in the combination arm was given for four 21-day cycles and was followed by osimertinib and pemetrexed (500 mg/m2) maintenance every 3 weeks. A total of 557 eligible patients were randomly assigned in a 1:1 ratio. The primary end point was investigator-assessed PFS.[51]Analysis of OS, a secondary end point, requires further follow-up (data maturity, 27%).

Grade 3 or higher adverse events from any cause were more common with the combination (64%) than with monotherapy (27%); this is consistent with known chemotherapy-related adverse events. Osimertinib plus pemetrexed with a platinum-based agent had a safety profile that was consistent with the established profiles of these agents.