Data reinforce adjuvant osimertinib as ‘practice-changing treatment’ in NSCLC subset
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Adjuvant osimertinib induced clinically meaningful reductions in central nervous system disease recurrence and death among patients with EGFR-mutated non-small cell lung cancer, according to data presented at the ESMO Virtual Congress 2020.
“Approximately 30% of patients with NSCLC present with resectable disease at diagnosis for which surgery with curative intent is the primary treatment ... however, rates of disease recurrence following surgery remain high across disease stages, regardless of postoperative chemotherapy use,” Masahiro Tsuboi, MD, researcher in the department of thoracic surgery and oncology at National Cancer Center Hospital East in Kashiwa, Japan, said during his presentation. “EGFR tyrosine kinase inhibitors are standard of care for patients with EGFR-metastatic NSCLC and previous studies have suggested there may be a role for EGFR TKIs in the resected setting.”
For the double-blind, multinational phase 3 ADAURA trial, Tsuboi and colleagues assessed the safety and efficacy of osimertinib (Tagrisso, AstraZeneca), a third-generation EGFR TKI, compared with placebo for patients with completely resected EGFR-mutated NSCLC.
Researchers randomly assigned patients 1:1 to 80 mg once-daily osimertinib (n = 339; median age, 64 years; 68% women; 64% Asian) or placebo (n = 343; median age, 62 years; 72% women; 64% Asian). Treatment continued for 3 years.
Investigator-assessed DFS among patients with stage II and stage IIIA disease served as the primary endpoint. Secondary endpoints included DFS in the overall population, OS and safety.
As HemOnc Today previously reported, results of an unplanned interim analysis showed osimertinib significantly improved DFS among patients with stage II to IIIA disease (median not reached vs. 19.6 months; HR = 0.17).
In the current study, researchers reported data from a prespecified exploratory analysis of disease recurrence patterns among all patients with stage IB to stage IIIA disease.
Median follow-up was 22 months.
Results, which were simultaneously published in The New England Journal of Medicine, showed a significant improvement in DFS among those assigned osimertinib (median not reached vs. 27.5 months; HR = 0.2; 99.12% CI, 0.14-0.3). DFS events occurred among 11% of patients in the osimertinib group vs. 46% of those assigned placebo.
Osimertinib-treated patients were more likely to have local or regional recurrence, with only 38% of patients in that group having metastatic recurrence compared with 61% of patients assigned placebo.
Researchers observed clinically meaningful improvements in CNS DFS with osimertinib (median, not reached vs. 48.2 months; HR = 0.18; 95% CI, 0.1-0.33), which corresponded to an 82% decrease in risk for CNS disease recurrence or death. The conditional probability of 12-month CNS recurrence was less than 1% with osimertinib compared with 7% with placebo.
Although OS data were immature, nine patients in the osimertinib group had died at the time of data cutoff vs. 20 patients in the placebo group.
No new safety concerns were observed, according to Tsuboi.
“The reduced risk for local and distant recurrence and improved CNS DFS in this study reinforce adjuvant osimertinib as a highly effective, practice-changing treatment for patients with stage IB to stage IIIA EGFR-metastatic NSCLC following complete tumor resection,” Tsuboi said.
References:
- Tsuboi M, et al. Abstract LBA1. Presented at: European Society for Medical Oncology Annual Meeting (virtual); Sept. 19-21, 2020.
- Wu YL, et al. N Eng J Med. 2020;doi:101056/NEJMoa2027071.
Perspective
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Johan F. Vansteenkiste, MD, PhD
The aim of treatment for patients in the stage IV setting is durable tumor control, measured by treatment-related adverse events and control of CNS disease. For patients with early-stage disease, improving cure rates is our aim mesaured by control of CNS disease and good tolerability.
This is a well-done study by Tsuboi and colleagues that was conducted in a baseline setting with complete resection plus adjuvant chemotherapy if indicated. These data are impressive, but early and immature. Of note, superior CNS control was observed with osimertinib. Minimal residual disease after surgery can be eliminated by cytotoxic chemotherapy and is likely to be eliminated by cytotoxic CD8-positive cells.
DFS may not be translated into better cure rates. I would like to see at least a 3-year OS difference. There is uncertainty about the role of osimertinib for everyone or at the time of relapse. Moreover, a substantial proportion of these patients are cured by surgery alone, so if we give osimertinib to every patient, it means about a 50% diarrhea rate and 25% skin problem rate for median duration of 22 months for all patients. There also is financial toxicity associated with osimertinib, so there is a crucial role here for measuring minimal residual disease for a selection of these patients. For adjuvant studies, there needs to be a lot of patients and patience.
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Tsuboi M, et al. Abstract LBA1. Presented at: European Society for Medical Oncology Annual Meeting (virtual); Sept. 19-21, 2020.
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