Intracranial Outcomes of De Novo Brain Metastases Treated With Osimertinib Alone in Patients With Newly Diagnosed EGFR-Mutant NSCLC

Author(s): Brandon S. Imber, MD, MA¹; Ryka Sehgal, MD²; Rachel Saganty, MD¹; Anne S. Reiner, MPH³; A. Turan Ilica, MD⁴; Emily Miao, PharmD¹; Bob T. Li, MD⁵; Gregory J. Riely, MD⁵; Helena A. Yu, MD⁵; Katherine S. Panageas, DrPH³; Robert J. Young, MD⁴; Luke R.G. Pike, MD, DPhil¹; Nelson S. Moss, MD¹

Source: https://doi.org/10.1016/j.jtocrr.2023.100607

Dr. Maen Hussein's Thoughts

Although Osimertinib in another trial (article from a previous month) had also impressive response first-line osimertinib initiation of 25 days. In total, 136 previously untreated brain metastases were tracked from baseline. Overall, 105 lesions (77.2%) had complete response and 31 had partial response reflecting best objective response of 100%.

INTRODUCTION

Patients with EGFR-mutant NSCLC have a high incidence of brain metastases. The EGFR-directed tyrosine kinase inhibitor osimertinib has intracranial activity, making the role of local central nervous system (CNS)-directed therapies, such as radiation and surgery, less clear.

METHODS

Patients with EGFR-mutant NSCLC and brain metastases who received osimertinib as initial therapy after brain metastasis diagnosis were included. Individual lesion responses were assessed using adapted RANO-BM criteria. CNS progression and local progression of brain metastasis from osimertinib start were analyzed using cumulative incidence treating death as a competing risk. Overall survival was estimated using Kaplan-Meier methodology.

RESULTS

There were 36 patients who had a median interval from brain metastasis diagnosis to first-line osimertinib initiation of 25 days. In total, 136 previously untreated brain metastases were tracked from baseline. Overall, 105 lesions (77.2%) had complete response and 31 had partial response reflecting best objective response of 100%. Best response occurred at a median of 96 days (range: 28–1113 d) from baseline magnetic resonance imaging. This reflects a best objective response rate of 100%. Two-year overall survival was 80%. CNS progression rates at 1-, 2-, and 3-years post-osimertinib were 21%, 32%, and 41%, respectively. Lesion-level local failure was estimated to be 0.7% and 4.7% at 1- and 2-years post-osimertinib, respectively. No clinicodemographic factors including brain metastasis number were associated with post-osimertinib progression.

CONCLUSIONS

Intracranial response to osimertinib is excellent for patients with EGFR-mutant NSCLC with de novo, previously untreated brain metastases. Very low local failure rates support a strategy of upfront osimertinib alone in selected patients.

Author Affiliations

¹Department of Radiation Oncology and Multidisciplinary Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, New York;²Department of Neurosurgery and Multidisciplinary Brain Metastasis Center, Memorial Sloan Kettering Cancer Center, New York, New York;³Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York;⁴Division of Neuroradiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;⁵Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York and Weill Cornell Medical College, New York, New York

Neoadjuvant PD-1 and PD-L1 Blockade With Chemotherapy for Borderline Resectable and Unresectable Stage III Non–Small Cell Lung Cancer

The phase II trial of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy in borderline resectable and unresectable stage III NSCLC showed a significant improvement in event-free survival (EFS) with the combination (24.1 vs 10.6 months) compared to chemotherapy alone, with a hazard ratio (HR) of 0.62. Major pathological response rates were higher with immunotherapy (44.7% vs 22.3%), and no new safety signals were noted. The regimen improved surgical resection rates (68% vs 52%) without increasing perioperative complications. This validates chemoIO in the neoadjuvant setting particularly in whom we wish to pursue resection or avoid chemoradiation. It would be great to see this compared to chemoradiation followed by immunotherapy rather than chemotherapy alone.

Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer

Results showed the median event-free survival (EFS) was 54.8 months with nivolumab plus ipilimumab vs 20.9 months with chemotherapy. Three-year EFS rates were 56% vs 44%. Three-year overall survival (OS) rates were 73% vs 61% pathologic complete response rates were 20.4% vs 4.6%. This was three cycles of nivolumab and one dose of ipilimumab vs chemotherapy.

Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study

Dato showed a confirmed overall response rate (ORR) of 42.7% with a complete response (CR) of 4.3%. The median duration of response was 7.0 months, with a disease control rate of 86.3% and a median overall survival (OS) of 15.6 months. This could be another option for EGFR mutant patients who had multiple lines of therapy.

Thoracic Radiotherapy Improves the Survival in Patients With EGFR-Mutated Oligo-Organ Metastatic Non–Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial

Patients were treated with thoracic and extrathoracic radiation to oligometastatic sites and it seems to help with improving survival, something to consider especially with SBRT now. Do our radiation oncologists have additional input?

A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor–Naïve EGFR-Mutant Metastatic Non–Small Cell Lung Cancer (RAMOSE trial)

Improved progression-free survival (PFS), now we have osimertinib and ramucirumab, amivantamab and Lazertinib (PFS 24.8 vs 23 months but NOT head to head).