In ASCO 2023, the highly anticipated results of the Adora study were unveiled, providing valuable insights into the efficacy and impact of adjuvant osimertinib in patients with resected stage one to stage three non-small cell lung cancer (NSCLC). This study presented the final overall survival data, complementing the previously reported disease-free survival data from 2020.
The findings, which were presented in the plenary session, shed light on the remarkable potential of osimertinib in improving patient outcomes and redefining treatment approaches for NSCLC.
The Adora Study
The Adora study was designed to investigate the efficacy of adjuvant osimertinib in patients with resected stage one to stage three NSCLC. It is important to note that the staging criteria have evolved since the study’s initiation, with today’s staging classifying the resected cases as stage two and stage three NSCLC.
This study specifically targeted a subset of patients whose tumors harbored an epidermal growth factor receptor (EGFR) mutation. Patients with the two most common mutations, known as Exon 19 deletions and L858R mutations, were randomly assigned to receive either osimertinib, a targeted therapy directed against the EGFR mutation, or a placebo.
Randomization occurred following surgery and completion of adjuvant chemotherapy. It is worth mentioning that while adjuvant chemotherapy was not mandatory, the majority of patients with stage two and stage three disease did receive it.
Unveiling the Results
The treatment duration in the Adora study spanned three years, comparing adjuvant osimertinib with a placebo. In terms of disease-free survival, the 2020 data revealed a significant improvement, with a hazard ratio of 0.2 for stage 1B to stage 3A. Upon updating the results in 2023, the hazard ratio remained strong, albeit slightly changed to 0.27. The focus of the recent update was on the overall survival outcomes, providing crucial information for clinicians and researchers.
The groundbreaking finding from the Adora study is that osimertinib led to a 50% reduction in death compared to placebo. Patients who received osimertinib exhibited a hazard ratio of 0.49, indicating a significant improvement in overall survival.
This compelling data has the potential to reshape clinical practice, as osimertinib’s remarkable ability to penetrate the central nervous system (CNS) has already contributed to a reduction in CNS metastases. Clinicians have increasingly adopted osimertinib due to its demonstrated efficacy in mitigating the morbidity associated with CNS metastasis.
What makes this study truly groundbreaking is that it is the first to demonstrate an overall survival improvement with an adjuvant tyrosine kinase inhibitor (TKI) in this setting.
The hazard ratio of 0.49 remained consistent across the key population of stage two and stage 3A NSCLC patients, which were the primary focus of the study. Furthermore, additional data presented in the study explored the use of adjuvant chemotherapy. Interestingly, the study revealed that the receipt of adjuvant chemotherapy did not significantly impact overall survival as long as patients received osimertinib as part of their treatment.
by: Tom John, MBBS, PhD, FRACP – Peter MacCallum Cancer Centre
Tom John is a medical oncologist specializing in thoracic malignancies, with a particular focus on lung cancer and mesothelioma, and his groundbreaking clinical trials and translational research have significantly impacted the field, leading to advancements in therapies and publications in prestigious journals such as the NEJM.
You can wath the interview here:
Toxicity and Discontinuation Rates
An essential aspect of any treatment evaluation is assessing its safety and tolerability. The Adora study provided valuable insights into the toxicity profile and discontinuation rates associated with osimertinib.
Notably, most instances of toxicity occurred within the first 12 months of treatment, with the most common side effects being diarrhea and rash. The rate of discontinuations was recorded at 13%, indicating a reasonable rate of dose interruption. While 27% of patients experienced treatment interruption, the actual rate of treatment discontinuation remained low.
Implications and Future Directions
Based on the findings of the Adora study, patients with resected stage two and three NSCLC, and tumors harboring an EGFR mutation, should be seriously considered for adjuvant osimertinib. Typically, these patients would receive osimertinib after completing chemotherapy, aligning with the majority of patients in the Adora study.
The study’s significant revelation is that the receipt or omission of adjuvant chemotherapy did not significantly impact overall survival, marking a significant advancement in the field. This pivotal study underscores the practice-changing potential of osimertinib and its role in transforming the treatment landscape for NSCLC.
Conclusion
The Adora study presented in ASCO 2023 provided critical insights into the efficacy and impact of adjuvant osimertinib in resected stage one to stage three NSCLC patients with EGFR mutations. With its impressive reduction in the risk of death and ability to penetrate the CNS, osimertinib has demonstrated its potential to revolutionize the treatment approach for NSCLC.
Ongoing research and clinical trials continue to explore the use of osimertinib in various settings, such as neoadjuvant or adjuvant therapy, and the investigation of resistance mechanisms. As the field progresses, osimertinib holds the promise of further advancements and the potential to transform the lives of even more patients in the future.