Adjuvant osimertinib in resected EGFR-mutant NSCLC - AstraZeneca
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Here is the REAL @Plenary_Session on #ADAURA #ASCO23 #ASCO2023 38.5% of people who had recurrence got OSI (very low!) That just...
Hey @JackWestMD, did you already see p25 of the #ADAURA supplementary appendix? Curious of your thoughts given 88% of pts in the placebo arm who developed progression and...
Before we all continue to pile on #ADAURA, can someone tell me % of patients who received Immunotherapy upon progression on IM-010 or KN-91. See figure. I will remind you that...
My analysis of ADAURA now on youtube in high resolution #ASCO23 ADAURA OS - Control arm participants who progressed got poor medical car... via @YouTube
Please check out this cost effectiveness analysis done by @LemmonOnc and I based on various projected final ADAURA OS results. We calculated that adjuvant osimertinib would be cost effective...
So only 79 of 343 patients (23%) in placebo arm got subsequent osimertinib in #ADAURA. Would love to see OS results subgrouped by those who got subsequent osi versus those who did...
"I have to start with #ADAURA because the Cheerleaders are out there in full force." Bring the truth, VP! Oncology has too many Cheerleaders. Put down the pom-poms and...
The average wholesale price of Osimertinib: $440,000. Shouldn't we ensure this OS benefit is real by running a trial with an appropriate control arm before bankrupting...
ADAURA; look at NEJM supplementary ; 7% 5y landmark advantage for those who got adjuvant chemo. My view will be to recommend adjuvant chemo before adjuvant osimertinib #ASCO23...
Thanks to @VivekSubbiah for giving @JackWestMD and I a chance to channel our debates into surprising consensus! #LCSM Lessons from ADAURA: Can we improve on a...
ADAURA is a landmark Phase III, double-blind, placebo-controlled trial that established adjuvant osimertinib (Tagrisso) as the standard of care for patients with completely resected stage IB-IIIA EGFR-mutant non-small cell lung cancer. The trial randomized 682 patients across 26 countries to receive osimertinib 80 mg daily or placebo for up to 3 years following surgery, with or without prior adjuvant chemotherapy. ADAURA is the first trial to demonstrate that a targeted EGFR therapy in the adjuvant setting translates a disease-free survival benefit into a statistically significant overall survival benefit.
Phase III, international, double-blind, 1:1 randomized, placebo-controlled trial in patients with completely resected stage IB-IIIA EGFR-mutant (exon 19 deletion or L858R) non-squamous NSCLC. EGFR mutations were identified prospectively using the cobas EGFR Mutation Test. Adjuvant chemotherapy was permitted but not mandated.
Adults with completely resected stage IB-IIIA (AJCC 7th edition) NSCLC harboring EGFR exon 19 deletions or L858R mutations, with WHO performance status 0-1. Approximately 60% of patients received adjuvant chemotherapy prior to randomization. Stratified by disease stage, mutation type, and race.
Osimertinib 80 mg orally once daily versus placebo for up to 3 years or until disease recurrence or unacceptable toxicity.
Primary endpoint: investigator-assessed disease-free survival (DFS) in patients with stage II-IIIA disease. Key secondary endpoints: DFS in the overall population (stage IB-IIIA), overall survival (OS), health-related quality of life, and safety. CNS DFS was a prespecified exploratory endpoint.
Osimertinib demonstrated a profound DFS benefit versus placebo. In the primary population (stage II-IIIA), DFS HR was 0.17 (99.06% CI: 0.11-0.26; p<0.001), representing an 83% reduction in the risk of recurrence or death. Median DFS was not reached with osimertinib versus 19.6 months with placebo. Updated analysis at 4 years showed sustained benefit with DFS HR of 0.23 (95% CI: 0.18-0.30). CNS DFS HR was 0.24 (95% CI: 0.14-0.42), demonstrating significant protection against brain metastases.
The planned final OS analysis demonstrated a statistically significant survival benefit. In stage II-IIIA patients, OS HR was 0.49 (95.03% CI: 0.33-0.73; p=0.0004), with 5-year OS rates of 85% versus 73%. In the overall population (stage IB-IIIA), OS HR was 0.49 (95.03% CI: 0.34-0.70; p<0.0001), with 5-year OS rates of 88% versus 78%. Osimertinib is the only EGFR TKI to demonstrate a significant OS benefit in the adjuvant setting.
The safety profile was consistent with known osimertinib toxicity. Most common adverse events were diarrhea (46% vs 20%), paronychia (25% vs 1%), and dry skin (23% vs 6%). Grade 3+ adverse events occurred in 20% of osimertinib patients versus 13% with placebo. Treatment discontinuation due to AEs was 11% versus 3%. No fatal AEs were reported with osimertinib. Extended follow-up showed no new safety signals, with grade 3+ AEs of 23% versus 14%.
ADAURA established adjuvant osimertinib as the standard of care for resected stage IB-IIIA EGFR-mutant NSCLC, with both DFS and OS benefits. The results underscore the importance of early EGFR mutation testing at diagnosis. Key clinical debates include the optimal treatment of stage IB patients, whether adjuvant chemotherapy adds benefit on top of osimertinib (subgroup analyses suggest it may not), the 3-year treatment duration question, and post-recurrence treatment strategies. ADAURA-2 (stage IA), NeoADAURA (neoadjuvant), and TARGET (5-year duration) are ongoing to address these questions.
