周一“星”视角|奥希替尼新辅助治疗Ⅰ-ⅢA期EGFR突变的NSCLC；未进行PET/CT分期与III期NSCLC生存率降低相关

01

Collin M. Blakely1,2, Anatoly Urisman2,3, Matthew A. Gubens1,2, Claire K. Mulvey1,2, Greg M. Allen1,2, Stephen C. Shiboski4, Julia K. Rotow5, Turja Chakrabarti1,2, D. Lucas Kerr1,2, Jacqueline V. Aredo1, Bianca Bacaltos2, Megan Gee2, Lisa Tan2, Kirk D. Jones3, W. Patrick Devine3,6, Robert C. Doebele7, Dara L. Aisner8, Tejas Patil7, Erin L. Schenk7, Trever G. Bivona1,2,9, Jonathan W. Riess 10, Melissa Coleman2,11, Johannes R. Kratz2,11, David M. Jablons2,11

1 Department of Medicine, University of California, San Francisco, San Francisco, CA

2 Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA

3 Department of Pathology, University of California, San Francisco, San Francisco, CA

4 Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA

5 Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA

6 Institute for Human Genetics, University of California, San Francisco, San Francisco, CA

7 Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO

8 Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO

9 Chan Zuckerberg Biohub, San Francisco, CA

10 Department of Medicine, University of California Davis, Sacramento, CA

11 Department of Surgery, University of California, San Francisco, San Francisco, CA

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.

[CITATION]: Blakely CM, Urisman A, Gubens MA, et al. Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study. J Clin Oncol. 2024 Jul 19:JCO2400071. 

[DOI]: 10.1200/JCO.24.00071

[IF]: 42.1

02

Gabriela Krakorova1, Petr Domecky2,3, Jiri Blazek1, Milos Pesek1, Ondrej Venclicek4, Libor Havel5, Michal Hrnciarik6, Jana Krejci7, Andrea Mullerova8, Miloslav Marel9, Jaroslav Duba2, Martin Svaton1

1 Department of Pneumology and Phthisiology, Faculty of Medicine and University Hospital in Pilsen, Charles University, Pilsen, Czech Republic.

2 OAKS Consulting s.r.o., Prague, Czech Republic.

3 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.

4 Department of Respiratory Diseases, Faculty of Medicine and University Hospital Brno, Masaryk University, Brno, Czech Republic.

5 Department of Respiratory Medicine, Thomayer Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

6 Pulmonary Department, University Hospital Hradec Kralove, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.

7 Department of Pneumology, Bulovka Hospital, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.

8 Department of Respiratory Medicine, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

9 Department of Pulmonology, University Hospital Motol, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.

Background: 

Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous stage due to its subgroups (IIIA–IIIC) comprising both resectable and unresectable tumors. Accurate determination of the extent of the disease is essential for excluding stage IV and choosing the optimal treatment regimen. Whole body positron emission tomography and computed tomography scan (PET/CT) is recommended as an initial staging imaging in locally advanced NSCLC. Despite international guidelines for NSCLC diagnosis and treatment, they are not always adhered to due to various reasons. Even in such a groundbreaking study, the phase 3 trial PACIFIC investigating the efficacy of durvalumab as consolidation therapy in patients with stage III NSCLC PET/CT was not mandatory. With the premise that whole body PET/CT of the trunk is essential for diagnosing stage III NSCLC, we performed a retrospective study evaluating the relationship of the use of PET/CT versus conventional staging with CT of the chest and abdomen, in terms of survival.

Methods: 

This retrospective study of stage III NSCLC patients used the Czech lung cancer registry LUCAS, which was established in June 2018. As of the data export (up to February 9, 2022), a total of 703 patients were eligible for the analysis. Overall survival (OS) was compared using Kaplan-Meier analysis and a Cox regression model. Continuous variables were tested using the Mann-Whitney test, and categorical variables using the Pearson’s Chi-square or Fisher’s exact test.

Results: 

A total of 703 patients were included in the cohort with an average age of 69 years. PET/CT was performed on 354 patients, and conventional staging using chest and abdominal CT on 349 patients. The median OS among patients with PET/CT was 20.9 months [95% confidence interval (CI): 18.1–23.7], and it was statistically significantly higher (P < 0.001) than among patients without PET/CT, where the median OS was 9.0 months (95% CI: 7.3–10.6). The observed effect of PET/CT was also statistically significant when comparing individual stages (IIIA, IIIB, IIIC). The multivariate Cox model confirmed the use of PET/CT as an independent prognostic factor. The most common reason for omission of PET/CT was the local or time unavailability of the examination.

Conclusions: 

Omission of PET/CT can mean a significant decrement in survival for the patients in stage III NSCLC, likely due to poor staging and suboptimal treatment. Routine use of PET/CT is strictly recommended for the optimal management of stage III NSCLC patients even outside the high-income countries.

[CITATION]: Gabriela Krakorova, Petr Domecky, Jiri Blazek, et al. Omission of staging PET/CT linked to reduced survival in stage III non-small cell lung cancer: insights from the LUCAS project real-world data. Transl Lung Cancer Res. 2024 Jul 30;13(7):1495-1504.

[DOI]: 10.21037/tlcr-24-108

[IF]: 4.0