Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: A Phase II Multicenter Study

Author(s): Collin M. Blakely, MD, PhD^1,2; Anatoly Urisman, MD, PhD^2,3; Matthew A. Gubens, MD, MS^1,2; Claire K. Mulvey, MD^1,2; Greg M. Allen, MD, PhD^1,2; Stephen C. Shiboski, PhD⁴; Julia K. Rotow, MD⁵; Turja Chakrabarti, MD, MS^1,2; D. Lucas Kerr, BS^1,2; Jacqueline V. Aredo, MD, MS¹; Bianca Bacaltos, MS²; Megan Gee, BS²; Lisa Tan, BS²; Kirk D. Jones, MD³; W. Patrick Devine, MD, PhD^3,6; Robert C. Doebele, MD, PhD⁷; Dara L. Aisner, MD, PhD⁸; Tejas Patil, MD⁷; Erin L. Schenk, MD, PhD⁷; Trever G. Bivona, MD, PhD⁹; Jonathan W. Riess, MD, MS¹⁰; Melissa Coleman, MD^2,11; Johannes R. Kratz, MD^2,11; David M. Jablons, MD^2,11

Source: https://doi.org/10.1200/JCO.24.00071

Dr. Anjan Patel's Thoughts

Neoadjuvant Osimertinib did not have a significant impact on major pathologic response and there were no ypCR’s after a median of ~8 weeks of therapy. I do think this shows a measurable response, enough such that I would consider Osi in a patient with “borderline resectable” disease.

PURPOSE

To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non–small cell lung cancer (NSCLC).

PATIENTS AND METHODS

This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.

RESULTS

A total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).

CONCLUSION

Treatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

Author Affiliations

¹Department of Medicine, University of California, San Francisco, San Francisco, CA; ²Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; ³Department of Pathology, University of California, San Francisco, San Francisco, CA; ⁴Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA; ⁵Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA; ⁶Institute for Human Genetics, University of California, San Francisco, San Francisco, CA; ⁷Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO; ⁸Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO; ⁹Chan Zuckerberg Biohub, San Francisco, CA; ¹⁰Department of Medicine, University of California Davis, Sacramento, CA; ¹¹Department of Surgery, University of California, San Francisco, San Francisco, CA

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