Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC
Osimertinib in adjuvant, now after chemotherapy and radiation, next… Neoadjuvant??? Trials are ongoing.
This is here till progression.
First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations – The UNICORN Phase 2 Nonrandomized Clinical Trial
Author(s): Yusuke Okuma, MD, PhD1; Kaoru Kubota, MD, PhD2; Mototsugu Shimokawa, PhD3; Kana Hashimoto, MD4; Yosuke Kawashima, MD5; Tomohiro Sakamoto, MD, PhD6; Hiroshi Wakui, MD, PhD7; Shuji Murakami, MD, PhD8; Kyoichi Okishio, MD, PhD9; Kenji Hayashihara, MD, PhD10; Yuichiro Ohe, MD, PhD1
Source: JAMA Oncol. 2024;10(1):43-51. doi:10.1001/jamaoncol.2023.5013
Dr. Anjan Patel's Thoughts
This study demonstrates activity of osimertinib in uncommon EGFR mutations. Of note, these were non-exon-20 mutations and included some with compound mutations. Response rates were reasonable and this justifies using targeted therapy in these uncommon subgroups.
IMPORTANCE
Non–small cell lung cancer (NSCLC) with uncommon EGFR mutations is a rare subgroup, composing 14% of all EGFR mutations.
OBJECTIVE
To determine the usefulness of osimertinib in previously untreated patients with metastatic NSCLC harboring uncommon EGFR mutations, excluding exon 20 insertion mutations.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, open-label, single-group, phase 2 nonrandomized clinical trial enrolled patients from April 10, 2020, to May 31, 2022, with a follow-up of 6 months from the date the last patient was enrolled. The study enrolled 42 patients with uncommon EGFR mutations, of whom 40 were eligible.
INTERVENTION
Osimertinib, 80 mg once daily, was administered orally to patients.
MAIN OUTCOMES AND MEASURES
The primary end point was the overall response rate (ORR). The secondary end points were disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), duration of response (DoR), and safety of osimertinib. Patients were included in the study on an intention-to-treat basis.
RESULTS
Of the 40 eligible patients, 22 were men (55.0%) and the median age was 72 years (range, 39.0-88.0 years). The most common mutations were G719X (20 [50.0%]), S768I (10 [25.0%]), and L861Q (8 [20.0%]). The ORR was 55.0% (90% CI, 40.9%-68.5%) and the DCR was 90.0% (95% CI, 76.3%-97.2%). The median PFS was 9.4 months (95% CI, 3.7-15.2 months) after a median follow-up of 12.7 months (range, 2.7-30.7 months). The median TTF was 9.5 months (95% CI, 5.6-30.3 months), median OS was not reached (NR; 95% CI, 19.3 months to NR), and median DoR was 22.7 months (95% CI, 9.5 months to NR). The ORR for patients with solitary or compound uncommon EGFR mutations was 45.5% (90% CI, 26.9%-65.3%) and 66.7% (90% CI, 43.7%-83.7%), respectively. Median PFS for patients with solitary or compound uncommon EGFR mutations was 5.4 months (95% CI, 3.6-22.7 months) and 9.8 months (95% CI, 5.1 months to NR), respectively. Median OS for patients with solitary or compound uncommon EGFR mutations was 23.0 months (95% CI, 12.3 months to NR) and NR, respectively. Median DoR for patients with solitary or compound uncommon EGFR mutations was 22.7 months (95% CI, 3.6-22.7 months) or NR (95% CI, 5.7 months to NR), respectively. Grade 3 or 4 adverse events were reported by 11 patients (27.5%), and 5 patients (12.5%) developed interstitial lung disease. All adverse events were manageable, and there were no treatment-related deaths.
CONCLUSIONS AND RELEVANCE
Osimertinib showed clinical activity with manageable toxic effects among previously untreated patients with metastatic NSCLC harboring uncommon EGFR mutations other than exon 20 insertion mutations. The results support the use of osimertinib as a treatment option for this patient population.
TRIAL REGISTRATION
Japan Registry of Clinical Trials Identifier: jRCTs071200002
Author Affiliations
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; 2Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 3Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; 4Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan; 5Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan; 6Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Tottori University Faculty of Medicine, Yonago, Tottori, Japan; 7Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan; 8Division of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan; 9National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; 10National Hospital Organization Ibarakihigashi National Hospital, Tokai-mura, Naka-gun, Ibaraki, JapanRelated Articles
Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC
Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo in the EGFR mutated patients. Osmiertinib shows efficacy in patients with EGFR mutation who underwent curative surgery or chemoradiotherapy.
Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC
Another possible option for first line NSCLC EGFR mutated (non-exon 20) is Osimertinib (osi). Osi and chemotherapy had less brain metastases. And with Amivantamab and Lazertinib (EGFR inhibitor), the combination had better PFS and OS (HR0.8). Higher toxicity though with 10% discontinuation vs 3% for Osimertinib. This is interim analysis, toxicity was EGFR related mostly.
Perioperative Nivolumab in Resectable Lung Cancer
Perioperative nivolumab (Nivo) showed a 20% 18-month EFPS improvement. This is another option to consider for your patients with stage IIA-IIIB NSCLC. Of note, the study arm received chemo + Nivo x 4 cycles preoperatively, then 12 months of Nivo therapy, and toxicities were as expected.
Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer
FCS medical oncologist and hematologist Ernesto Bustinza-Linares, MD has co-authored an abstract published in the American Society of Clinical Oncology Journal, JCO Precision Oncology, that uncovers a new testing method to determine personalized care options for patients with metastatic non-small cell lung cancer (NSCLC). The abstract’s authors address the limitations of existing guidelines that recommend checkpoint immunotherapy, sometimes in combination with chemotherapy, for treating NSCLC, which often discounts patient variability and immune factors. The findings from the study show that by incorporating additional plasma proteome-based testing, combined with the standard protein inhibitor testing, clear differences in patient outcomes were observed after applying targeted treatments based on the testing results.
