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

First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations

Progression-free survival (PFS) was higher in the Sun group vs chemotherapy, 10.3 m vs 7.5 m with HR of .65 with higher responses (58.9% vs 31.1%) diarrhea high CK and anemia were the most common side effects. The issue is that amivan was not part of treatment and compared to chemotherapy ami in addition to chemotherapy had 11m PFS also in this trial few had brain mets so no evaluation for CNS protection or treatment. But an oral agent in patients who don’t want to come to the office often.

Selpercatinib in Early-Stage RET Fusion–Positive Non–Small-Cell Lung Cancer

109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib and 61% with placebo (HR for disease recurrence, progression, or death, 0.17 P<0.001). Patients with stage IB, II, or IIIA non–small-cell lung cancer (NSCLC), event-free survival at 2 years was 94% with selpercatinib and 70% with placebo. Genomic testing is expanding now for early stage NSCLC. More study in the adjuvant setting showing promise with targeted therapy.

Ensartinib in Resected ALK-Positive Non–Small-Cell Lung Cancer

It seems the old cliche of more drugs than patients is becoming true for most providers here. The data needs to mature further here but likely this will be another option for Anaplastic lymphoma kinase (ALK)+ non–small-cell lung cancer (NSCLC) patients in the adjuvant setting. It does look like CNS protection benefits are meaningful as well.

Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China

The median overall survival (OS) was 27·9 months with ivonescimab versus 23·7 months with tis.

Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial

Median progression-free survival was significantly longer with sac-TMT plus pembrolizumab than with pembrolizumab alone (not reached vs 5·7 m) this is regardless of PDL-1 expression (1-49 or >50).