The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended osimertinib for the adjuvant treatment of adult patients with stage IB, II, or IIIA EGFR-mutated non–small cell lung cancer following complete tumor resection with curative intent.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended osimertinib (Tagrisso) for the adjuvant treatment of adult patients with stage IB, II, or IIIA EGFR-mutated non–small cell lung cancer (NSCLC) following complete tumor resection with curative intent.1
The indication would include patients whose tumors have exon 19 deletions or exon 21 (L858R) mutations.
The positive opinion was based on phase 3 findings of the ADAURA trial, in which osimertinib demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared with placebo in the primary analysis population of patients with stage II and IIIA EGFR-mutant disease, and also in the overall group of patients with stage IB to IIIA NSCLC.2
In those with stage II and IIIA NSCLC, the median DFS with osimertinib had not yet been reached in patients who received osimertinib compared with 19.6 months in those who received placebo (HR, 0.17; 99.06% CI, 0.11-0.26; P <.0001). The median DFS was not yet reached vs 27.5 months in the investigative and control arms, respectively, in the overall population (HR, 0.20; 99.12% CI, 0.14-0.30; P <.0001).
“With no targeted treatment options currently available for early-stage lung cancer patients after surgery in the EU, recurrence rates remain unacceptably high,” said Dave Fredrickson, executive vice president, Oncology Business Unit. “This positive recommendation is a vital step towards introducing a targeted treatment option for these patients for the first time. It also reinforces the urgency to test all lung cancer patients for tumor mutations before making any treatment decisions to ensure that as many patients as possible can benefit from innovative therapies, like Tagrisso, when they become available.”
In the phase 3 ADAURA trial, investigators enrolled 682 patients with NSCLC that harbored EGFR exon 19 deletions or exon 21 L858R mutations, who had complete tumor resection, with or without previous adjuvant chemotherapy. Patients were randomized 1:1 to receive either oral osimertinib at 80 mg once daily or placebo following recovery from surgery and standard adjuvant chemotherapy, if administered.
To be eligible for enrollment, patients needed to have resectable tumors that was stage IB to IIIA, predominant nonsquamous histology, and the aforementioned mutations, which were prospectively detected from tumor tissue via the cobas EGFR Mutation Test in a central laboratory.
The primary objective of the trial is DFS per investigator assessment. Secondary end points comprise DFS in the overall population; DFS at 2, 3, 4, and 5 years; overall survival (OS), safety, and health-related quality of life.
Preliminary findings were presented during the 2020 ASCO Virtual Scientific Program. Here the median DFS in patients with stage II to IIIA disease had not yet been reached with osimertinib arm vs 20.4 months with placebo (HR, 0.17; 95% CI, 0.12-0.23; P <.0001).3
At 2 years, the DFS rates in stage IB disease were 87% vs 73% (HR, 0.50; 95% CI, 0.25-0.96), respectively, in patients who received osimertinib vs placebo. These rates were 91% vs 56%, respectively, in those with stage II disease (HR, 0.17; 95% CI, 0.08-0.31) and 88% vs 32%, respectively, in those with stage IIIA disease (HR, 0.12; 95% CI, 0.07-0.20).
Overall survival (OS) data remain immature; 29 patients died overall (9 on osimertinib and 20 on placebo). The median OS has not yet been reached in either arm (HR, 0.40; 95% CI, 0.18-0.90).
Regarding safety, the most frequent adverse effects in those who received osimertinib included laboratory abnormalities such as lymphopenia, leukopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough.
In December 2020, the FDA approved osimertinib for use in this setting, as detected by an FDA-approved test, also based on the ADAURA findings. Most recently, in April 2020, the China National Medical Products Administration approved the third-generation TKI for use in the adjuvant setting of patients with early-stage NSCLC with EGFR exon 19 deletions or exon 21 mutations, following tumor resection with curative intent, with or without adjuvant chemotherapy as recommended by the patient’s physician.