Skip to main content
Log in

Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell lung cancer: a retrospective analysis

  • Research Article
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B + PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B + PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P < 0.001). The incidence of grade ⩾ 3 adverse events was higher in the B + PP group than in the PP group (27.3% vs. 10.8%, respectively; P = 0.204). Univariate and multivariate analyses suggested that the receipt of ⩾ 5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394–424

    Article  Google Scholar 

  2. Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature 2018; 553(7689): 446–454

    Article  CAS  Google Scholar 

  3. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100(1): 57–70

    Article  CAS  Google Scholar 

  4. Kerbel RS. Tumor angiogenesis. N Engl J Med 2008; 358(19): 2039–2049

    Article  CAS  Google Scholar 

  5. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001; 7(9): 987–989

    Article  CAS  Google Scholar 

  6. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008; 8(8): 579–591

    Article  CAS  Google Scholar 

  7. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355(24): 2542–2550

    Article  CAS  Google Scholar 

  8. Zhou C, Wu YL, Chen G, Liu X, Zhu Y, Lu S, Feng J, He J, Han B, Wang J, Jiang G, Hu C, Zhang H, Cheng G, Song X, Lu Y, Pan H, Zheng W, Yin AY. BEYOND: a randomized, double-blind, placebo-controlled, multicenter, phase III study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer. J Clin Oncol 2015; 33(19): 2197–2204

    Article  CAS  Google Scholar 

  9. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 2009; 27(8): 1227–1234

    Article  CAS  Google Scholar 

  10. Cohen MH, Gootenberg J, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin) plus carboplatin and paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist 2007; 12(6): 713–718

    Article  CAS  Google Scholar 

  11. Balducci L, Ershler WB. Cancer and ageing: a nexus at several levels. Nat Rev Cancer 2005; 5(8): 655–662

    Article  CAS  Google Scholar 

  12. Crinò L, Dansin E, Garrido P, Griesinger F, Laskin J, Pavlakis N, Stroiakovski D, Thatcher N, Tsai CM, Wu YL, Zhou C. Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study. Lancet Oncol 2010; 11(8): 733–740

    Article  Google Scholar 

  13. Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advancedstage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol 2008; 26(1): 60–65

    Article  CAS  Google Scholar 

  14. Zhu J, Sharma DB, Gray SW, Chen AB, Weeks JC, Schrag D. Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA 2012; 307(15): 1593–1601

    Article  CAS  Google Scholar 

  15. Takeoka H, Yamada K, Naito Y, Matsuo N, Ishii H, Tokito T, Azuma K, Ichiki M, Hoshino T. Phase II trial of carboplatin and pemetrexed plus bevacizumab with maintenance bevacizumab as a first-line treatment for advanced non-squamous non-small cell lung cancer in elderly patients. Anticancer Res 2018; 38(6): 3779–3784

    Article  CAS  Google Scholar 

  16. Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Pereira JR, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009; 374(9699): 1432–1440

    Article  CAS  Google Scholar 

  17. Belani CP, Brodowicz T, Ciuleanu TE, Krzakowski M, Yang SH, Franke F, Cucevic B, Madhavan J, Santoro A, Ramlau R, Liepa AM, Visseren-Grul C, Peterson P, John WJ, Zielinski CC. Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study. Lancet Oncol 2012; 13(3): 292–299

    Article  CAS  Google Scholar 

  18. Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2013; 31(23): 2895–2902

    Article  CAS  Google Scholar 

  19. Lopez-Chavez A, Young T, Fages S, Leon L, Schiller JH, Dowlati A, Brahmer JR, Johnson DH, Sandler A. Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis. J Thorac Oncol 2012; 7(11): 1707–1712

    Article  CAS  Google Scholar 

  20. Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol 2013; 31(34): 4349–4357

    Article  CAS  Google Scholar 

  21. Soo RA, Loh M, Mok TS, Ou SH, Cho BC, Yeo WL, Tenen DG, Soong R. Ethnic differences in survival outcome in patients with advanced stage non-small cell lung cancer: results of a meta-analysis of randomized controlled trials. J Thorac Oncol 2011; 6(6): 1030–1038

    Article  Google Scholar 

Download references

Acknowledgements

We thank the patients for participating in this study. This work was supported by the National Key R&D Program of China (No. 2018YFC1313201), the Innovation Project of Shandong Academy of Medical Sciences (No. 2019-04), and the Academic Promotion Program of Shandong First Medical University (No. 2019ZL002).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hui Zhu or Jinming Yu.

Additional information

Compliance with ethics guidelines

Yaru Tian, Hairong Tian, Xiaoyang Zhai, Hui Zhu, and Jinming Yu declare that they have no competing interests. All procedures involving patients were conformed to Declaration of Helsinki. All patients provided written informed consent before their participation in this study.

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tian, Y., Tian, H., Zhai, X. et al. Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell lung cancer: a retrospective analysis. Front. Med. 16, 610–617 (2022). https://doi.org/10.1007/s11684-021-0827-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-021-0827-8

Keywords

Navigation