Comparative effectiveness of nivolumab versus standard of care for third-line patients with small-cell lung cancer
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: To estimate the comparative effectiveness of nivolumab versus standard of care (SOC) in terms of overall survival (OS) for small-cell lung cancer patients treated with two prior lines of chemotherapy, in other words, third line in the USA. Materials & methods: Data were from CheckMate 032, a single-arm trial of nivolumab, and real-world electronic patient records. Comparisons of OS were conducted using three different methods to adjust for differences (regression, weighting and doubly robust) between the populations. Results: Nivolumab was associated with longer survival compared with SOC (hazard ratio for OS: 0.58–0.70) across all methods for adjustment. Conclusion: Nivolumab was more efficacious in terms of OS as third-line treatment for small-cell lung cancer compared with current SOC in the USA.
Lay abstract
Small-cell lung cancer is an aggressive disease and often patients require multiple treatments to help them live longer. In this study, we looked at how long patients survived when receiving nivolumab compared with other commonly used therapies as their third treatment (known as third line) in the USA. Data came from the CheckMate 032 single-arm clinical trial of nivolumab and real-world electronic patient records from a US database where patients received standard of care treatment. We used several analysis methods and found that patients treated with nivolumab survived for longer than patients treated with standard of care in the USA. There is a high unmet need in the third-line small-cell lung cancer population and results from this study will help inform decision makers of the potential therapeutic option of nivolumab treatment.
Supplementary Material
File (appendix.docx)
- Download
- 693.61 KB
References
1.
Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer 121(5), 664–672 (2015).
2.
Van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet 378(9804), 1741–1755 (2011).
3.
Alvarado-Luna G, Morales-Espinosa D. Treatment for small cell lung cancer, where are we now?: a review. Transl. Lung Cancer Res. 5(1), 26–38 (2016).
4.
American Joint Committee on Cancer. Lung. In: AJCC Cancer Staging Manual. 8th Edition Springer, NY, USA (2016).
5.
Früh M, De Ruysscher D, Popat S, Crino L, Peters S, Felip E. Small-cell lung cancer (SCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 24(Suppl. 6), vi99–vi105 (2013).
6.
Rudin CM, Ismaila N, Hann CL et al. Treatment of small-cell lung cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians guideline. J. Clin. Oncol. 33(34), 4106–4111 (2015).
7.
National Comprehensive Cancer Network. Small cell lung cancer (version 1.2020) (2019). https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf
8.
Horn L, Mansfield AS, Szczesna A et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N. Engl. J. Med. 379(23), 2220–2229 (2018).
9.
Paz-Ares L, Dvorkin M, Chen Y et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, Phase III trial. Lancet 394(10212), 1929–1939 (2019).
10.
De Jong WK, Ten Hacken NH, Groen HJ. Third-line chemotherapy for small cell lung cancer. Lung Cancer 52(3), 339–342 (2006).
11.
Schwartzberg L, Korytowsky B, Penrod J et al. Developing a real-world 3L comparator to CheckMate 032: overall survival (OS) in patients with small cell lung cancer (SCLC). Presented at: 19th World Conference on Lung Cancer (WCLC 2018) of the International Association for the Study of Lung Cancer (IASLC). Toronto, Ontario, Canada, 23–26 September 2018.
12.
Minami S, Ogata Y, Ihara S, Yamamoto S, Komuta K. Retrospective analysis of outcomes and prognostic factors of chemotherapy for small-cell lung cancer. Lung Cancer (Auckl.) 7, 35–44 (2016).
13.
Ready N, Farago AF, De Braud F et al. Third-line nivolumab monotherapy in recurrent small cell lung cancer: checkMate 032. J. Thorac. Oncol. 14(2), 237–244 (2018).
14.
Antonia SJ, Lopez-Martin JA, Bendell JC et al. Checkmate 032: nivolumab (N) alone or in combination with ipilimumab (I) for the treatment of recurrent small cell lung cancer (SCLC). J. Clin. Oncol. 34(Suppl. 15), 100–100 (2016).
15.
US FDA. FDA approves pembrolizumab for metastatic small cell lung cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-metastatic-small-cell-lung-cancer
16.
Chung HC, Piha-Paul SA, Lopez-Martin J et al. Pembrolizumab after two or more lines of prior therapy in patients with advanced small-cell lung cancer (SCLC): results from the KEYNOTE-028 and KEYNOTE-158 studies. Presented at: AACR Annual Meeting. Atlanta, GA, USA, (July 2019) (Abstract CT073).
17.
Faria R, Hernandez Alava M, Manca A, Wailoo A. NICE DSU Technical Support Document 17: The Use of Observational Data to Inform Estimates of Treatment Effectiveness in Technology Appraisal: Methods for Comparative Individual Patient Data. NICE, Sheffield, UK (2015).
18.
Phillippo DM, Ades AE, Dias S, Palmer S, Abrams KR, Welton KJ. NICE DSU Technical Support Document 18: Methods for Population-Adjusted Indirect Comparisons in Submissions to NICE. NICE, Sheffield, UK (2016).
19.
Demedts IK, Vermaelen KY, Van Meerbeeck JP. Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. Eur. Respir. J. 35(1), 202–215 (2010).
20.
Hurwitz JL, Mccoy F, Scullin P, Fennell DA. New advances in the second-line treatment of small cell lung cancer. The Oncologist 14(10), 986–994 (2009).
21.
Chan BA, Coward JI. Chemotherapy advances in small-cell lung cancer. J. Thoracic Dis. 5(Suppl. 5), S565–S578 (2013).
22.
Pallis AG, Agelidou A, Agelaki S et al. A multicenter randomized Phase II study of the irinotecan/gemcitabine doublet versus irinotecan monotherapy in previously treated patients with extensive stage small-cell lung cancer. Lung Cancer 65(2), 187–191 (2009).
23.
Lammers PE, Shyr Y, Li C-I et al. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J. Thoracic Oncol. 9(4), 559–562 (2014).
24.
Pietanza MC, Kadota K, Huberman K et al. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin. Cancer Res. 18(4), 1138–1145 (2012).
25.
Cope S, Popoff E, Keeping S et al. PCN21 – Comparative efficacy of nivolumab ± ipilimumab versus standard of care (SOC) for third-line (3L) patients with recurrent small cell lung cancer (SCLC) using population-adjusted indirect comparison. Value Health 21(Suppl. 3), S18 (2018).
26.
Cope S, Keeping ST, Goldgrub R et al. Indirect comparison of nivolumab ± ipilimumab (CheckMate 032) versus other treatments for recurrent small-cell lung cancer. J. Comp. Eff. Res. 8(10), 733–751 (2019).
Information & Authors
Information
Published In
Pages: 1275 - 1284
PubMed: 33140652
Copyright
© 2020 Sam Keeping. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License
History
Received: 3 July 2020
Accepted: 23 September 2020
Published online: 3 November 2020
Keywords:
Topics
Authors
Funding Information
Metrics & Citations
Metrics
Article Usage
Article usage data only available from February 2023. Historical article usage data, showing the number of article downloads, is available upon request.
Citations
How to Cite
Comparative effectiveness of nivolumab versus standard of care for third-line patients with small-cell lung cancer. (2020) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2020-0134
Export citation
Select the citation format you wish to export for this article or chapter.
Citing Literature
- Rumbidzai Takundwa, Gaurav Suri, Franziska Dirnberger, Andre Verhoek, Elizabeth Vinand, Jessie Wang, Stephen Puntis, Xerxes Pundole, Fiona Blackhall, Matching-Adjusted Indirect Treatment Comparison of Tarlatamab Versus Comparator Therapies in England in Patients with Extensive-Stage Small Cell Lung Cancer Who Have Received Two or More Prior Lines of Therapy, Advances in Therapy, 10.1007/s12325-025-03376-4, 42, 12, (6078-6090), (2025).
- Jessie Wang, Gautam Sajeev, Xinglei Chai, Rumbidzai Takundwa, Franziska Dirnberger, Xerxes Pundole, Malaika Pastel, Hongbo Yang, Umit Tapan, Efficacy outcomes between tarlatamab and real-world physicians’ choice of therapies for previously treated extensive stage small cell lung cancer, The Oncologist, 10.1093/oncolo/oyaf256, 30, 9, (2025).
- Jair Bar, Qingqing Xu, Sudeep Karve, Pooja Hingorani, Amin A. Virani, Neal E. Ready, Real‐World Response and Survival Outcomes and Treatment Patterns in Patients With Extensive Stage Small‐Cell Lung Cancer Receiving Third‐Line Treatment, Cancer Reports, 10.1002/cnr2.70289, 8, 8, (2025).
- Eunso Lee, Jeong Yun Jang, Jinho Yang, Uncommon Adverse Events of Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Systematic Review of Case Reports, Cancers, 10.3390/cancers16101896, 16, 10, (1896), (2024).
- Julie E. Park, Harlan Campbell, Kevin Towle, Yong Yuan, Jeroen P. Jansen, David Phillippo, Shannon Cope, Unanchored Population-Adjusted Indirect Comparison Methods for Time-to-Event Outcomes Using Inverse Odds Weighting, Regression Adjustment, and Doubly Robust Methods With Either Individual Patient or Aggregate Data, Value in Health, 10.1016/j.jval.2023.11.011, 27, 3, (278-286), (2024).
- Jing Zhao, Xiaoli Zhuo, Lei Liu, Zhe Yang, Guobin Fu, Opportunities and challenges of immune checkpoint inhibitors for extensive‐stage small‐cell lung cancer, Cancer Innovation, 10.1002/cai2.23, 1, 2, (183-193), (2022).
- 皓悦 王, Research on Targeting and Immunotherapy of Small Cell Lung Cancer, Advances in Clinical Medicine, 10.12677/ACM.2022.1281009, 12, 08, (7005-7011), (2022).
- Apar Kishor P. Ganti, Billy W. Loo, Michael Bassetti, Collin Blakely, Anne Chiang, Thomas A. D'Amico, Christopher D'Avella, Afshin Dowlati, Robert J. Downey, Martin Edelman, Charles Florsheim, Kathryn A. Gold, Jonathan W. Goldman, John C. Grecula, Christine Hann, Wade Iams, Puneeth Iyengar, Karen Kelly, Maya Khalil, Marianna Koczywas, Robert E. Merritt, Nisha Mohindra, Julian Molina, Cesar Moran, Saraswati Pokharel, Sonam Puri, Angel Qin, Chad Rusthoven, Jacob Sands, Rafael Santana-Davila, Michael Shafique, Saiama N. Waqar, Kristina M. Gregory, Miranda Hughes, Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology, Journal of the National Comprehensive Cancer Network, 10.6004/jnccn.2021.0058, 19, 12, (1441-1464), (2021).
- Caitlin Smare, Kiran Dave, Ariadna Juarez-Garcia, Pranav Abraham, John R. Penrod, D. Ross Camidge, Yong Yuan, Cost-effectiveness of nivolumab monotherapy in the third-line treatment of small cell lung cancer, Journal of Medical Economics, 10.1080/13696998.2021.1974763, 24, 1, (1124-1133), (2021).