Found 1 Presentation For Request "1173p"
1173P - Induction osimertinib in EGFR-mutant stage IIIA/B NSCLC
- Waleed Kian (Beer Sheva, Israel)
Abstract
Background
Definitive chemoradiation (CRT) followed by durvalumab is the standard of care in stage III NSCLC. Osimertinib showed high efficacy in metastatic and resectable settings and is currently assessed in unresectable IIIA/B. This study aimed at testing the efficacy of osimertinib as induction therapy before definitive radiotherapy (RT) in EGFRm stage III patients to induce tumor shrinkage and reduction of the radiation field.
Methods
This phase 2 open-label study enrolled EGFRm NSCLC stage IIIA/B patients. Osimertinib (80 mg) was given daily for a maximum of 12 weeks followed by definitive RT and/or surgery. Response to therapy was assessed by PET-CT at weeks 3, 6, and 12. In case of response, patients were referred to sequential definitive RT at week 12 while in case of progression, patients were referred to CRT. After RT+/- surgery or CRT, patients were followed (no adjuvant therapy). ORR is the primary endpoint, secondary endpoints are: mPFS, gross tumor volume (GTV) and planned target volume (PTV) before and after treatment. All the patients will be followed for 2 years.
Results
This preliminary analysis includes 13 patients (11 female; age 73.0 ± 5.4 years) with a median follow-up of 13.5 months. All non-smokers with adenocarcinoma. 9 patients harbored exon 19 del, 3 L858R, and 1 had a rare mutation. T status was T1, T2, T3, and T4 in 2, 9, 1, and 1 and N status was N2 and N3 in 10 & 3 patients respectively. Thus, stage IIIA, B, and C were in 5, 5, and 3 patients. Among 9 patients who have completed 12 weeks of osimertinib therapy, ORR was 100%, (2 CR, 7 PR, 0 SD or PD), 3 are still on osimertinib, and 1 withdrew (unrelated adverse events). Following osimertinib induction, 6 patients completed RT & 1 underwent surgery (pT1aN0) without RT. The other 2 pts are still under RT. Pre-osimertinib GTV & PTV were 20.2 ± 42.9 cm3 and 196.4 ± 241.5 cm3 respectively. Both were reduced to 12.8±21.8 cm3 (-36.7%) and 181.9±113.0 cm3 (-7.4%), respectively. Data are immature for PFS. No safety issues reported.
Conclusions
Osimertinib induction in stage III EGFRm NSCLC is feasible and led to tumor shrinkage in 92% of the cases, resulting in a significant reduction of the radiation field and enabling preservation of the lung tissue radiation-induced toxicity. This chemotherapy-free novel approach should be further investigated as an alternative to CRT in this setting for EGFRm patients.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca, N. Peled.
Disclosure
N. Peled: Financial Interests, Institutional, Funding, This is an investigator-initiated study, funded by AstraZeneca, who did not have a role in collection, analysis, interpretation, or writing of this report. All other authors have declared no conflicts of interest.