|The following article features coverage from the European Society for Medical Oncology 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
The risk of developing disease recurrence in the CNS was reported to be significantly lower and clinically meaningful in patients with completely resected non-small cell lung cancer (NSCLC) treated with osimertinib compared with placebo. The results were drawn from of a prespecified exploratory analysis of data from the phase 3 ADAURA trial and presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.1
Use of small-molecule targeted therapy has proven to be very effective in the setting of advanced/metastatic NSCLC for patients with tumors that have specific actionable genomic alterations, such as EGFR inhibitors for patients with disease characterized by the EGFR-sensitizing mutations, ex19del and L858R. Furthermore, results of previously conducted studies of EGFR inhibitors, such as erlotinib, in patients with completely resected nonmetastatic NSCLC have suggested a role for these agents in the adjuvant setting.
The phase 3 ADAURA trial (ClinicalTrials.gov Identifier: NCT02511106) is a double-blind, placebo-controlled study of 682 adult patients with completely resected stage IB to IIIA nonsquamous NSCLC characterized by an EGFR-sensitizing mutation, most of whom had previously received treatment with adjuvant chemotherapy, and who were subsequently randomly assigned in a 1:1 ratio to receive the third-generation EGFR inhibitor, osimertinib, or placebo.
Previously reported results of this study demonstrated that the hazard ratio for disease-free survival (DFS) in patients with stage II/IIIA disease, the primary study endpoint, was 0.17 (99.06% CI, 0.11-0.26; P <.0001) for those receiving osimertinib compared with placebo.1,2
In this prespecified exploratory analysis of data from the ADAURA trial including 682 patients across 24 countries, the patterns of disease recurrence were investigated. Particular attention was paid to disease recurrence in the CNS given its association with poor prognosis.
At a median follow-up of 22 months, 11% of patients in the osimertinib arm and 46% of those in the placebo arm experienced a DFS event characterized by disease recurrence or death. The presence of distant disease represented disease recurrence in 38% and 61% of those receiving osimertinib and placebo, respectively.
Furthermore, a CNS DFS event occurred in 2% and 11% of those receiving osimertinib and placebo, respectively, with 1% of patients treated with osimertinib and 10% of those receiving placebo experiencing a CNS recurrence.
Median CNS DFS was not reached in the osimertinib arm and was 48.2 months in the placebo arm (hazard ratio [HR], 0.18; 95% CI, 0.10-0.33; P <.0001). This translates into an 82% reduction in risk of CNS disease recurrence or death when osimertinib is used in the adjuvant setting in this patient cohort.
Results for overall survival, a secondary study endpoint, were immature at the time of this analysis.
In his concluding remarks, the presenting author Masahiro Tsuboi, MD, PhD, director of the department of thoracic surgery and oncology, National Cancer Center Hospital East in Japan, stated that “the reduced risk of local and distant recurrence and improved CNS DFS reinforce adjuvant osimertinib as a highly effective, practice-changing treatment for patients with stage IB/II/IIIA EGFR-mutant NSCLC following complete tumor resection.”
While it appears there may be “superior CNS control with osimertinib” in this patient cohort, commented Johan Vansteenkiste, MD, PhD, of the University Hospitals Leuven, Campus Gasthuisberg, Belgium, in a discussion following the main presentation, he also noted that DFS might not translate to better cure rates. The drug also comes with financial toxicity as well as literal toxicity: Dr Vansteenkiste pointed out that 50% of patients receiving osimertinib had diarrhea and approximately 25% had skin problems for a duration of 22 months. Ultimately, he predicted, minimal residual disease (MRD) will have a crucial role in the selection of patients eligible to receive the drug.
ESMO President Solange Peters, MD, asked the discussant group: Could osimertinib become the standard of care in this NSCLC type, even in the absence of mature OS data?
“Of course, Solange, one wants overall survival,” responded Roy Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center in New Haven, Connecticut, and vice chair for developmental therapeutics for the Southwestern Oncology Group (SWIOG) Lung Committee. “But I think right now the compelling nature of these data, in my mind, make [osimertinib] something we should use as we await those results.” Dr Herbst added that by late 2020, “we’ll have quality of life [data].”
And when Dr Peters mentioned some of the concerns that have been raised surrounding unblinding and how treatment crossover in the trial could complicate future survival analyses, Dr Herbst said: “The trial remains blinded at the level of the patient and the doctor — we’ve only unblinded it at the data — and we are committed to a crossover. So actually, an amendment is going through at many places — it should be through at most sites now — where patients will get the osimertinib on recurrence.”
Disclosures: Research funding for this study was provided by AstraZeneca. Some of the authors reported financial relationships with pharmaceutical companies. For a full list of disclosures, please refer to the study abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.
- Tsuboi M, Wu Y-L, He J, et al. Osimertinib adjuvant therapy in patients (pts) with resected EGFR mutated (EGFRm) NSCLC (ADAURA): Central nervous system (CNS) disease recurrence. Presented at: European Society of Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract LBA1.
- Wu Y-L, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. Published online September 19, 2020. doi:10.1056/NEJMoa2027071