The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Osimertinib significantly improved disease-free survival in patients with stage Ib-IIIa EGFR-positive non-small cell lung cancer (NSCLC) after complete tumor resection, according to a late-breaking abstract presented during the plenary session at the ASCO20 Virtual Scientific Program.

Adjuvant osimertinib resulted in a 79% reduction in the risk of disease recurrence or death compared with placebo (hazard ratio (HR)=0.21; 95% CI, 0.16-0.28; P <.0001). At 2-years, 89% of patients who received osimertinib were alive and did not experience cancer recurrence.

“Adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB/II/IIIa EGFR mutation-positive NSCLC after complete tumor resection,” said Roy S. Herbst, MD, of Yale School of Medicine and Yale Cancer Center, in New Haven, during a press conference. “It is metastasis, the spread of tumor, that kills patients. Drugs such as this, based on biology, given to patients at the earliest possible time to prevent those metastasis, allow patients to live longer with better quality of life.”

The phase 3 ADAURA trial (ClinicalTrials.gov Identifier: NCT02511106) included 682 patients with EGFR-mutated NSCLC who had complete resection of the disease. Patients were randomly assigned to third-generation EGFR-TKI osimertinib 80 mg once daily or placebo for up to 3 years. If patients were candidates for chemotherapy, they started before going on oral osimertinib. The primary endpoint was disease-free survival in patients with stage II-IIIa patients.  


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An independent data monitoring committee unblinded the trial due to early efficacy.

For patients with stage II-IIIa disease, the median disease-free survival was not yet reached for osimertinib compared with 20.4 months for placebo. Osimertinib resulted in an 83% reduction in risk for disease recurrence (HR=0.17; 95% CI, 0.12-0.23; P <.0001). The median disease-free survival at 2 years for patients with stage II-IIIa disease was 90% with osimertinib compared with 44% with placebo.

“The ADAURA placebo arm reminds us again that even following successful surgery and chemotherapy as appropiate there remains a high degree of disease recurrence in resectable early-stage lung cancer,” Dr. Herbst explained.

A key secondary endpoint of the trial was disease-free survival adding in stage Ib patients. Among this larger group of patients, the median disease-free survival was not reached for osimertinib compared with 28.1 months for placebo. Osimertinib resulted in a 79% reduced risk for disease recurrence. The median disease-free survival at 2 years was 89% for osimertinib compared with 53% for placebo.

A subgroup analysis showed that osimertinib resulted in improved disease-free survival in every category examined, including sex, age, smoking status, race, stage of disease, and EGFR mutation type.

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“A consistent improvement was seen regardless of whether patients had seen prior adjuvant chemotherapy,” Dr Herbst remarked. “All results are favoring the study drug: osimertinib.”

Analysis of disease-free survival by stage showed that 2-year disease-free survival rates for osimertinib were consistent across all stages at 87%, 91%, and 88% for stage Ib, II, and IIIa, respectively. In contrast the 2-year disease-free survival rates decreased with increasing disease stage for the placebo arms.

The median duration of exposure for osimertinib was 22.3 months compared with 18.4 months with placebo. Osimertinib was well tolerated with a safety profile consistent with its known safety profile. There were no adverse events leading to death in the osimertinib arm. Grade 1/2 interstitial lung disease was reported in 3% of patients who received osimertinib. Corrected QT prolongation was reported in 7% of patients assigned osimertinib and 1% of patients assigned placebo.

Survival follow-up is ongoing.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2020 meeting by visiting the conference page.

Reference

Herbst RS, Tsuboi M, John T, et al. Osimertinib as adjuvant therapy in patients (pts) with stage IB-IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr LBA5.