November 20, 2020 - Osimertinib in combination with platinum plus pemetrexed was well tolerated in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer.
Osimertinib (Tagrisso) in combination with platinum plus pemetrexed was well tolerated in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer (NSCLC), according to preliminary safety results from the OPAL study (NEJ032C/LOGIK1801).1
Ryo Morita, MD, chief of respiratory medicine, at Akita Kousei Medical Center in Akita City, Japan, said that that investigators have detected no new safety signals in the phase 2, multicenter trial during a presentation at the ESMO Asia Virtual Congress 2020.
“The follow-up is ongoing and we believe that the results of the OPAL study will provide valuable information regarding the safety and preliminary efficacy of treatment for the FLAURA 2 study and will impact the future treatment strategy for EGFR-mutated NSCLC.”
Frontline osimertinib monotherapy is currently the standard of care for patients with previously untreated EGFR-mutated NSCLC. Despite its efficacy as a single agent in the first line, patients experience disease progression after approximately 19 months on treatment. OPAL is the first study to explore the safety and efficacy of osimertinib in combination with platinum-based chemotherapy in patients with treatment-naïve EGFR-mutated advanced NSCLC. Investigators hypothesize that the combination will help prolong response based on data from trials such as the NEJ009 study in which gefitinib (Iressa) in combination with carboplatin plus pemetrexed demonstrated a better response rates and progression-free survival over gefitinib alone.2,3
Investigators recruited 67 across 24 Japanese medical centers. Patients were assigned to 80 mg daily osimertinib plus 75 mg/m2 cisplatin or carboplatin (target above the curve = 5), followed by 500 mg/m2pemetrexed administered every 3 weeks for up to 4 cycles. Patients who did not experience disease progression after 4 cycles of induction therapy continued osimertinib/pemetrexed until progression or unacceptable toxicity. Thirty-four patients were assigned to the cisplatin arm while 33 were included in the carboplatin arm.1
As of the March 31, 2020, data cutoff, 5 (14.7%) patients in the cisplatin arm discontinued treatment due to adverse events (AEs) compared with 1 (3.0%) in the carboplatin arm. All patients in the study experienced AEs, although grade 3 or higher AEs were more common in the carboplatin cohort (84.8% vs 70.6%, respectively).
In the cisplatin arm, lymphocyte count decreased (32.4%) followed by neutropenia (23.5%) and anemia (8.8%) were the most common grade 3 or higher AEs. In the carboplatin arm, the most common grade 3 or higher AE was neutropenia (51.5%) followed by thrombocytopenia (39.4%), anemia (27.3%), and lymphocyte count decreased (27.3%).
Twenty-eight patients in both cohorts remain on treatment with 1 patient in each group discontinuing due to disease progression.
Osimerinib is currently the standard of care for patients with previously untreated EGFR-mutated NSCLC based on the results of the phase 3 FLAURA trial (NCT02296125). Patients with locally advanced or metastatic EGFR-mutant NSCLC were assigned to frontline treatment with osimertinib (n = 279) versus first-generation erlotinib (Tarceva) or gefitinib (n = 277). Results showed osimertinib induced superior progression-free survival in the entire population (HR, 0.46; P < .001), in patients with central nervous system (CNS) metastases (HR, 0.47; P <.001), and those without CNS metastases (HR, 0.46; P <.001).4
Data for the secondary end point of overall survival (OS) also favored the osimertinib. The median OS was 38.6 months (95% CI, 34.5-41.8) versus 31.8 months (95% CI, 26.6-36.0) in the comparator group (HR, 0.80; 95.05% CI, 0.64-1.00; P =.046). At 3 years, 28% of patients remained on treatment in the osimertinib cohort versus 9% in the comparator cohort.
Investigators observed grade 3 or higher AEs in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. Twenty-seven percent of patients in both groups experienced serious AEs.
Investigators of the phase 3 FLAURA 2 study (NCT04035486) will randomize approximately 586 patients to receive osimertinib alone or osimertinib with either pemtrexed and cisplatin or carboplatin.
In October 2020, the FDA accepted a supplemental new drug application from AstraZeneca, the manufacturer of osimertinib, and granted the anti-EGFR tyrosin kinase inhibitor a priority review for the adjuvant treatment of patients with early-stage EGFR-mutated NSCLC following complete tumor resection with curative intent. Results from the double-blind, randomized, placebo-controlled ADAURA trial (NCT02511106) presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program showed that the disease-free survival was not reached with osimertinib (95% CI, 38.8–not calculated) versus 20.4 months (95% CI, 16.6-24.5) with placebo (HR, 0.17; 95% CI, 0.12-0.23; P < .0001) in patients with stage II/IIA disease.5