周一“星”视角|围手术期使用纳武利尤单抗治疗可切除肺癌的价值；非小细胞肺癌患者治疗前情绪压力与免疫检查点抑制剂反应的关系

01

Tina Cascone1, Mark M Awad1, Jonathan D Spicer1, Jie He1, Shun Lu1, Boris Sepesi1, Fumihiro Tanaka1, Janis M Taube1, Robin Cornelissen1, Libor Havel1, Nina Karaseva1, Jaroslaw Kuzdzal1, Lubos B Petruzelka1, Lin Wu 1, Jean-Louis Pujol1, Hiroyuki Ito1, Tudor-Eliade Ciuleanu1, Ludmila de Oliveira Muniz Koch1, Annelies Janssens1, Aurelia Alexandru1, Sabine Bohnet1, Fedor V Moiseyenko1, Yang Gao1, Yasutaka Watanabe1, Cinthya Coronado Erdmann1, Padma Sathyanarayana1, Stephanie Meadows-Shropshire1, Steven I Blum1, Mariano Provencio Pulla1; CheckMate 77T Investigators

1 From the University of Texas M.D. Anderson Cancer Center, Houston (T.C., B.S.); Dana-Farber Cancer Institute, Boston (M.M.A.); McGill University Health Centre, Montreal (J.D.S.); the National Cancer Center-National Clinical Research Center for Cancer-Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.H.), Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (S.L.), and Hunan Cancer Hospital (L.W.) and Xiangya Hospital, Central South University (Y.G.), Changsha - all in China; the University of Occupational and Environmental Health, Kitakyushu (F.T.), Kanagawa Cancer Center, Yokohama (H.I.), and Saitama Cancer Center, Saitama (Y.W.) - all in Japan; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore (J.M.T.); Erasmus MC Cancer Institute, Rotterdam, the Netherlands (R.C.); Thomayer Hospital (L.H.) and Charles University (L.B.P.) - both in Prague, Czech Republic; St. Petersburg State Budgetary Healthcare Institution, Clinical Oncology Dispensary (N.K.), and St. Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (F.V.M.) - both in St. Petersburg, Russia; Jagiellonian University Collegium Medicum, John Paul II Hospital, Krakow, Poland (J.K.); Montpellier Regional University Hospital, Montpellier, France (J.-L.P.); Prof. Dr. Ion Chiricuta and Universitatea de Medicina si Farmacie Iuliu Hatieganu, Cluj-Napoca (T.-E.C.), and Institutul Oncologic București Prof. Dr. Alexandru Trestioreanu, Bucharest (A.A.) - both in Romania; Hospital Israelita Albert Einstein, São Paulo (L.O.M.K.); Antwerp University Hospital, Edegem, Belgium (A.J.); Universitätsklinikum Schleswig-Holstein, Lübeck, Germany (S.B.); Bristol Myers Squibb, Princeton, NJ (C.C.E., P.S., S.M.-S., S.I.B.); and Hospital Universitario Puerta de Hierro, Madrid (M.P.P.).

Background: 

Standard treatment with neoadjuvant nivolumab plus chemotherapy significantly improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative treatment (i.e., neoadjuvant therapy followed by surgery and adjuvant therapy) with nivolumab may further improve clinical outcomes.

Methods: 

In this phase 3, randomized, double-blind trial, we assigned adults with resectable stage IIA to IIIB NSCLC to receive neoadjuvant nivolumab plus chemotherapy or neoadjuvant chemotherapy plus placebo every 3 weeks for 4 cycles, followed by surgery and adjuvant nivolumab or placebo every 4 weeks for 1 year. The primary outcome was event-free survival according to blinded independent review. Secondary outcomes were pathological complete response and major pathological response according to blinded independent review, overall survival, and safety.

Results: 

At this prespecified interim analysis (median follow-up, 25.4 months), the percentage of patients with 18-month event-free survival was 70.2% in the nivolumab group and 50.0% in the chemotherapy group (hazard ratio for disease progression or recurrence, abandoned surgery, or death, 0.58; 97.36% confidence interval [CI], 0.42 to 0.81; P < 0.001 A pathological complete response occurred in 25.3% of the patients in the nivolumab group and in 4.7% of those in the chemotherapy group (odds ratio, 6.64; 95% CI, 3.40 to 12.97); a major pathological response occurred in 35.4% and 12.1%, respectively (odds ratio, 4.01; 95% CI, 2.48 to 6.49). Grade 3 or 4 treatment-related adverse events occurred in 32.5% of the patients in the nivolumab group and in 25.2% of those in the chemotherapy group.

Conclusion:

Perioperative treatment with nivolumab resulted in significantly longer event-free survival than chemotherapy in patients with resectable NSCLC. No new safety signals were observed.

[CITATION]: Cascone T, Awad MM, Spicer JD, et al. Perioperative Nivolumab in Resectable Lung Cancer, N Engl J Med. 2024 May 16;390(19):1756-1769.

[DOI]: 10.1056/NEJMoa2311926

[IF]:158.5

02

Yue Zeng1 2, Chun-Hong Hu1 3, Yi-Zheng Li1 4, Jian-Song Zhou2, Shu-Xing Wang1 5, Meng-Dong Liu6, Zhen-Hua Qiu1, Chao Deng1, Fang Ma1, Chun-Fang Xia1, Fei Liang7, Yu-Rong Peng1, Ao-Xi Liang1, Sheng-Hao Shi1, Shi-Jiao Yao1, Jun-Qi Liu1, Wen-Jie Xiao1 5, Xiao-Qiao Lin1 5, Xin-Yu Tian1 5, Ying-Zhe Zhang1, Zhuo-Ying Tian1, Ji-An Zou1 5, Yun-Shu Li1 5, Chao-Yue Xiao1, Tian Xu1, Xiao-Jie Zhang2, Xiao-Ping Wang2, Xian-Ling Liu1, Fang Wu1 2 3 8 9 10

1 Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.

2 National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China.

3 Hunan Cancer Mega-Data Intelligent Application and Engineering Research Centre, Changsha, China.

4 Key Laboratory of Molecular Radiation Oncology Hunan Province, Xiangya Hospital, Central South University, Changsha, China.

5 Xiangya School of Medicine, Central South University, Changsha, China.

6 Department of Psychology, University of Washington, Seattle, WA, USA.

7 Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, China.

8 Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

9 Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha, China.

10 FuRong Laboratory, Changsha, China.

Background: 

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer.

Methods: 

ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale.

Results: 

The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002).On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes.

Conclusion: 

This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management.

[CITATION]: Zeng Y, Hu C. H, Li Y. Z, et al. Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer. Nat Med 2024.

[DOI]: 10.1038/s41591-024-02929-4.

[IF]:82.9