Feasibility Study of Nivolumab in Combination with Carboplatin Plus Paclitaxel and Concurrent Thoracic Radiation in Patients with Untreated Unresectable Locally Advanced Non-Small Cell Lung Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Sep 28

PMID 39335099

Authors

Yuta Yamanaka

Takayo Ota

Yutaka Masuoka

Yuki Takeyasu

Satoaki Nakamura

Masaaki Terashima

Hiroshige Yoshioka

Masahiro Fukuoka

Takayasu Kurata

Affiliations

Soon will be listed here.

Abstract

Despite advancements in diagnosing and treating non-small cell lung cancer (NSCLC), the prognosis remains poor. Immune checkpoint inhibitors have shown promise in enhancing survival rates. Therefore, this study aimed to investigate the safety of nivolumab administration with concurrent chemoradiation therapy (CCRT) in patients with unresectable locally advanced NSCLC. Twelve patients with unresectable locally advanced NSCLC at Kansai Medical University Hospital and Izumi City General Medical Center were enrolled from May 2018 to September 2020. They received nivolumab (360 mg) tri-weekly twice, weekly carboplatin (AUC 2 min × mg/mL) and paclitaxel (40 mg/m) for 6 weeks, and thoracic radiotherapy (60 Gy/30 fractions), followed by maintenance nivolumab therapy (360 mg, tri-weekly) for 6 months. The primary endpoint was incidence of dose-limiting toxicities (DLTs), and the secondary endpoints included safety, response rate, progression-free survival (PFS), overall survival (OS), 2-year survival rate, and treatment completion rate. Three patients completed the protocol. Nine discontinued due directly to interstitial pneumonia (three) and pneumonia (one). Ten patients (83.3%) experienced a grade 3 or higher event, of which three (25%) experienced a grade 4 or higher event, and of these, one (8.3%) experienced a grade 5 event. Three patients experienced DLTs. Concurrent nivolumab with CCRT was tolerated in unresectable locally advanced NSCLC, which offers potential treatment benefits.

References

Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S . Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol. 2010; 28(20):3299-306. DOI: 10.1200/JCO.2009.24.7577. View

Antonia S, Villegas A, Daniel D, Vicente D, Murakami S, Hui R . Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(20):1919-1929. DOI: 10.1056/NEJMoa1709937. View

Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S . Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010; 28(23):3739-45. DOI: 10.1200/JCO.2009.24.5050. View

Jabbour S, Berman A, Decker R, Lin Y, Feigenberg S, Gettinger S . Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial. JAMA Oncol. 2020; 6(6):848-855. PMC: 7042914. DOI: 10.1001/jamaoncol.2019.6731. View

Peters S, Felip E, Dafni U, Tufman A, Guckenberger M, Alvarez R . Progression-Free and Overall Survival for Concurrent Nivolumab With Standard Concurrent Chemoradiotherapy in Locally Advanced Stage IIIA-B NSCLC: Results From the European Thoracic Oncology Platform NICOLAS Phase II Trial (European Thoracic Oncology.... J Thorac Oncol. 2020; 16(2):278-288. DOI: 10.1016/j.jtho.2020.10.129. View

Curran Jr W, Paulus R, Langer C, Komaki R, Lee J, Hauser S . Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011; 103(19):1452-60. PMC: 3186782. DOI: 10.1093/jnci/djr325. View

Rahim M, Okholm T, Jones K, McCarthy E, Liu C, Yee J . Dynamic CD8 T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell. 2023; 186(6):1127-1143.e18. PMC: 10348701. DOI: 10.1016/j.cell.2023.02.021. View

Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum R . Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014; 124(2):687-95. PMC: 3904601. DOI: 10.1172/JCI67313. View

Borghaei H, Paz-Ares L, Horn L, Spigel D, Steins M, Ready N . Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17):1627-39. PMC: 5705936. DOI: 10.1056/NEJMoa1507643. View

10.

Antonia S, Villegas A, Daniel D, Vicente D, Murakami S, Hui R . Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018; 379(24):2342-2350. DOI: 10.1056/NEJMoa1809697. View

11.

Theelen W, Chen D, Verma V, Hobbs B, Peulen H, Aerts J . Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med. 2020; 9(5):467-475. DOI: 10.1016/S2213-2600(20)30391-X. View

12.

Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F . Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 378(22):2078-2092. DOI: 10.1056/NEJMoa1801005. View

13.

Dovedi S, Adlard A, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle E . Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014; 74(19):5458-68. DOI: 10.1158/0008-5472.CAN-14-1258. View

14.

Bradley J, Hu C, Komaki R, Masters G, Blumenschein G, Schild S . Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2019; 38(7):706-714. PMC: 7048161. DOI: 10.1200/JCO.19.01162. View

15.

Liang H, Deng L, Chmura S, Burnette B, Liadis N, Darga T . Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing. J Immunol. 2013; 190(11):5874-81. PMC: 3660450. DOI: 10.4049/jimmunol.1202612. View

16.

Calvert A, Newell D, Gumbrell L, OReilly S, Burnell M, Boxall F . Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989; 7(11):1748-56. DOI: 10.1200/JCO.1989.7.11.1748. View

17.

Peters S, Felip E, Dafni U, Belka C, Guckenberger M, Irigoyen A . Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-radiotherapy regimen in stage III non-small cell lung cancer-The ETOP NICOLAS trial. Lung Cancer. 2019; 133:83-87. DOI: 10.1016/j.lungcan.2019.05.001. View

18.

Jabbour S, Lee K, Frost N, Breder V, Kowalski D, Pollock T . Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. JAMA Oncol. 2021; . PMC: 8446818. DOI: 10.1001/jamaoncol.2021.2301. View

19.

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J . Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 379(21):2040-2051. DOI: 10.1056/NEJMoa1810865. View

20.

Senan S, Brade A, Wang L, Vansteenkiste J, Dakhil S, Biesma B . PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2016; 34(9):953-62. DOI: 10.1200/JCO.2015.64.8824. View