Abstract
Background
Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need.
Patients and methods
Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry.
Results
A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0–1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months).
Conclusion
Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic.
Similar content being viewed by others
Change history
09 July 2018
Clinical and Translational Oncology.
References
International Agency for Research on Cancer (IARC). Latest world. Cancer Statistics. IARC, Lyon, France; 2013.
Berrino F. The EUROCARE study: strengths, limitations and perspectives of population-based, comparative survival studies. Ann Oncol. 2003;14(Suppl 5):v9–13.
Morgensztern D, Ng SH, Gao F, Govindan R. Trends in stage distribution for patients with non-small cell lung cancer: a National Cancer Database survey. J Thorac Oncol. 2010;5(1):29–33.
Cufer T, Ovcaricek T, O’Brien ME. Systemic therapy of advanced non-small cell lung cancer: major-developments of the last 5-years. Eur J Cancer. 2013;49(6):1216–25.
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542–50.
Kader Y, Le Chevalier T, El-Nahas T, Sakr A. Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation. Oncol Targets Ther. 2013;6:803–9.
Weiss JM, Stinchcombe TE. Second-line therapy for advanced NSCLC. Oncologist. 2013;18(8):947–53.
Sanofi-Aventis U.S. TAXOTERE, prescribing information, (docetaxel) Injection concentrate, intravenous infusión (IV), NJ, USA. 2013; 6 Eli Lilly and Company Limited. Alimta (pemetrexed) summary of product characteristics; 2012.
Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008;26:3543–51.
Roche Products Limited. Tarceva (erlotinib) summary of product characteristics; 2014.
Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicenter, double-blind, randomised phase 3 trial. Lancet. 2014;384:665–73.
Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowsky M, et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-LUNG 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014;15:143–55.
Borghaei H, Paz-Ares L, Horn L, Spigel D, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Eng J Med. 2015;373:1627–39.
Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Eng J Med. 2015;373:123–35.
Commmitee for Medicinal Products for Human Use (CHMP). European Medicines Agency Assessment report of Opdivo. EMA/246304/2016; 2016.
Garon EB, Rizvi NQ, Hui R, Leigh N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Eng J Med. 2015;372:2018–28.
Funding
No funding was provided for this research work.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no relevant affiliations with any organization or entity with a financial interest in with the subject matter or materials discussed in the manuscript.
Ethical approval
This study was approved by the Local Research Ethics Committees and was executed in accordance with the Declaration of Helsinki, Good Clinical Practice, and local ethical and legal requirements.
Informed consent
All enrolled patients signed informed consent.
Rights and permissions
About this article
Cite this article
Garde-Noguera, J., Martin-Martorell, P., De Julián, M. et al. Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients. Clin Transl Oncol 20, 1072–1079 (2018). https://doi.org/10.1007/s12094-017-1829-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-017-1829-5