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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

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Front. Med.    2022, Vol. 16 Issue (4) : 610-617    https://doi.org/10.1007/s11684-021-0827-8
RESEARCH ARTICLE
Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell lung cancer: a retrospective analysis
Yaru Tian1, Hairong Tian1,2, Xiaoyang Zhai1, Hui Zhu1(), Jinming Yu1()
1. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan 250117, China
2. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan 250117, China
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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.
Keywords bevacizumab      elderly patient      advanced non-small-cell lung cancer      overall survival      toxicity     
Corresponding Author(s): Hui Zhu,Jinming Yu   
About author:

Tongcan Cui and Yizhe Hou contributed equally to this work.
Just Accepted Date: 07 December 2021   Online First Date: 14 March 2022    Issue Date: 02 September 2022
 Cite this article:   
Yaru Tian,Hairong Tian,Xiaoyang Zhai, et al. Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell lung cancer: a retrospective analysis[J]. Front. Med., 2022, 16(4): 610-617.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0827-8
https://academic.hep.com.cn/fmd/EN/Y2022/V16/I4/610
Characteristic 　 Number of patients (%) ?P
Total B+ PP (n = 22) PP (n = 37)
Age, year 　 　 　 　
?Median 69 69 69 　
?Range 65–85 65–76 65–85 　
??≥ 69 34 13 (59.1) 21 (56.8) ?0.861
??< 69 25 9 (40.9) 16 (43.2)
Sex 　 　 　 　
?Male 41 13 (59.1) 28 (75.7) ?0.181
?Female 18 9 (40.9) 9 (24.3)
KPS score 　 　 　 　
?≥ 80 56 20 (90.9) 36 (97.3) ?0.640
?< 80 3 2 (9.1) 1 (2.7)
Smoking status 　 　 　 　
?Never smoker 24 10 (45.5) 14 (37.8) ?0.565
?Ever smoker 35 12 (54.5) 23 (62.2)
Histology 　 　 　 　
?Adenocarcinoma 58 21 (95.5) 37 (100) ?0.373
?Others 1 1 (4.5) 0 (0)
Stage 　 　 　 　
?IIIB 11 6 (27.3) 5 (13.5) ?0.334
?IV 48 16 (72.7) 32 (86.5)
Hypertension 　 　 　 　
?Yes 16 5 (22.7) 11 (29.7) ?0.559
?No 43 17 (77.3) 26 (70.3)
EGFR mutation status assessmenta 42 16 26 　
?EGFR mutation positive 16 5 (31.3) 11 (42.3) ?0.474
?EGFR wild type 26 11 (68.8) 15 (57.7)
Tab.1  Patient characteristics
Treatment 　 Number of patients (%) ??P
Total B+ PP (n = 22) PP (n = 37)
Number of first-line chemotherapy cycles 　 　 　
?Median 5 4 6 　
?Range 2–9 2–9 2–9 　
??≥ 5 32 9 (40.9) 23 (62.2) ??0.113
??< 5 27 13 (59.1) 14 (37.8)
Maintenance 　 　 　 　
?Yes 31 7 (31.8) 24 (64.9) ??0.014
?No 28 15 (68.2) 13 (35.1)
Maintenance regimens 31 7 24 　
?Bevacizumab+ pemetrexed 7 6 1 　
?Pemetrexed
?TKIs		 22
2		 1
0		 21
2		 　
Thoracic radiation 　 　 　 　
?Yes 16 6 (27.3) 10 (27.0) ??0.984
?No 43 16 (62.3) 27 (73.0)
Second-line treatment 　 　 　 　
?Yes 28 8 (72.7) 20 (83.3) ??0.785
?No 7 3 (27.3) 4 (16.7)
Second-line regimens
?Chemotherapy
?TKIs		 19
9		 5 (62.5)
3 (37.5)		 14 (70.0)
6 (30.0)		 ??1.000
Tab.2  Treatment details of the two groups
Fig.1  PFS and OS in the entire cohort.
Fig.2  Comparison of OS between the B+ PP and PP groups.
Fig.3  Comparison of PFS between the B+ PP and PP groups.
Characteristic mOS, month 1-Year OS, % 2-Year OS, % Chi-square statistic P
Age, year 　 　 　 　 　
?≥ 69 25.4 86.6 60.5 3.13 0.077
?< 69 NR 91.0 75.9
Sex 　 　 　 　 　
?Male 33.3 89.6 70.1 0.32 0.569
?Female NR 83.7 62.7
KPS score 　 　 　 　 　
?≥ 80 33.4 89.7 74.2 4.98 0.026
?< 80 22.6 66.7 0.0
Smoking status 　 　 　 　 　
?Never smoker NR 89.3 71.4 1.58 0.209
?Ever smoker 33.3 87.6 65.3
Stage 　 　 　 　 　
?IIIB 25.4 64.3 64.3 1.40 0.237
?IV 33.4 91.2 66.9
EGFR mutation status assessment 　 　 　
?EGFR mutation positive 37.2 79.1 69.2 0.37 0.542
?EGFR wild type 33.4 95.2 71.1
Number of first-line chemotherapy cycles 　 　 　
?≥ 5 37.2 100.0 95.0 12.52 <0.001
?< 5 22.6 74.6 42.6
Maintenance 　 　 　 　 　
?Yes NR 93.1 74.8 2.64 0.104
?No 33.3 82.6 55.1
Thoracic radiation 　 　 　 　
?Yes NR 93.3 62.2 0.35 0.555
?No 33.3 87.1 67.8
Bevacizumab 　 　 　 　 　
?Yes 20.5 70.3 0.0 14.68 <0.001
?No 33.4 97.0 81.9
Tab.3  Univariate analysis of prognostic factors for overall survival in elderly patients with advanced NSCLC
Characteristic HR 95% CI Chi-square statistic P
Age, year (≥ 69 vs. < 69) 2.023 0.513–7.977 1.013 0.314
Sex (male vs. female) 0.891 0.131–6.043 0.014 0.906
Number of first-line chemotherapy cycles (≥ 5 vs. < 5) 0.045 0.005–0.426 7.288 0.007
Maintenance (yes vs. no) 0.864 0.218–3.419 0.043 0.835
Thoracic radiation (yes vs. no) 0.176 0.015–2.117 1.875 0.171
Bevacizumab (yes vs. no) 13.733 1.855–101.675 6.579 0.010
Tab.4  Multivariate analysis of the prognostic factors for OS in elderly patients with advanced ns-NSCLC
1 F Bray, J Ferlay, I Soerjomataram, RL Siegel, LA Torre, A Jemal. 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
https://doi.org/10.3322/caac.21492 pmid: 30207593
2 RS Herbst, D Morgensztern, C Boshoff. The biology and management of non-small cell lung cancer. Nature 2018; 553(7689): 446–454
https://doi.org/10.1038/nature25183 pmid: 29364287
3 D Hanahan, RA Weinberg. The hallmarks of cancer. Cell 2000; 100(1): 57–70
https://doi.org/10.1016/S0092-8674(00)81683-9 pmid: 10647931
4 RS Kerbel. Tumor angiogenesis. N Engl J Med 2008; 358(19): 2039–2049
https://doi.org/10.1056/NEJMra0706596 pmid: 18463380
5 RK Jain. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001; 7(9): 987–989
https://doi.org/10.1038/nm0901-987 pmid: 11533692
6 LM Ellis, DJ Hicklin. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008; 8(8): 579–591
https://doi.org/10.1038/nrc2403 pmid: 18596824
7 A Sandler, R Gray, MC Perry, J Brahmer, JH Schiller, A Dowlati, R Lilenbaum, DH Johnson. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355(24): 2542–2550
https://doi.org/10.1056/NEJMoa061884 pmid: 17167137
8 C Zhou, YL Wu, G Chen, X Liu, Y Zhu, S Lu, J Feng, J He, B Han, J Wang, G Jiang, C Hu, H Zhang, G Cheng, X Song, Y Lu, H Pan, W Zheng, AY Yin. 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
https://doi.org/10.1200/JCO.2014.59.4424 pmid: 26014294
9 M Reck, J von Pawel, P Zatloukal, R Ramlau, V Gorbounova, V Hirsh, N Leighl, J Mezger, V Archer, N Moore, C Manegold. 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
https://doi.org/10.1200/JCO.2007.14.5466 pmid: 19188680
10 MH Cohen, J Gootenberg, P Keegan, R Pazdur. 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
https://doi.org/10.1634/theoncologist.12-6-713 pmid: 17602060
11 L Balducci, WB Ershler. Cancer and ageing: a nexus at several levels. Nat Rev Cancer 2005; 5(8): 655–662
https://doi.org/10.1038/nrc1675 pmid: 16056261
12 L Crinò, E Dansin, P Garrido, F Griesinger, J Laskin, N Pavlakis, D Stroiakovski, N Thatcher, CM Tsai, YL Wu, C Zhou. 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
https://doi.org/10.1016/S1470-2045(10)70151-0 pmid: 20650686
13 SS Ramalingam, SE Dahlberg, CJ Langer, R Gray, CP Belani, JR Brahmer, AB Sandler, JH Schiller, DH; Eastern Cooperative Oncology Group Johnson. Outcomes for elderly, advanced-stage 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
https://doi.org/10.1200/JCO.2007.13.1144 pmid: 18165641
14 J Zhu, DB Sharma, SW Gray, AB Chen, JC Weeks, D Schrag. Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA 2012; 307(15): 1593–1601
https://doi.org/10.1001/jama.2012.454 pmid: 22511687
15 H Takeoka, K Yamada, Y Naito, N Matsuo, H Ishii, T Tokito, K Azuma, M Ichiki, T Hoshino. 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
https://doi.org/10.21873/anticanres.12661 pmid: 29848743
16 T Ciuleanu, T Brodowicz, C Zielinski, JH Kim, M Krzakowski, E Laack, YL Wu, I Bover, S Begbie, V Tzekova, B Cucevic, JR Pereira, SH Yang, J Madhavan, KP Sugarman, P Peterson, WJ John, K Krejcy, CP Belani. 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
https://doi.org/10.1016/S0140-6736(09)61497-5 pmid: 19767093
17 CP Belani, T Brodowicz, TE Ciuleanu, M Krzakowski, SH Yang, F Franke, B Cucevic, J Madhavan, A Santoro, R Ramlau, AM Liepa, C Visseren-Grul, P Peterson, WJ John, CC Zielinski. 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
https://doi.org/10.1016/S1470-2045(11)70339-4 pmid: 22336221
18 LG Paz-Ares, F de Marinis, M Dediu, M Thomas, JL Pujol, P Bidoli, O Molinier, TP Sahoo, E Laack, M Reck, J Corral, S Melemed, W John, N Chouaki, AH Zimmermann, C Visseren-Grul, C Gridelli. 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
https://doi.org/10.1200/JCO.2012.47.1102 pmid: 23835707
19 A Lopez-Chavez, T Young, S Fages, L Leon, JH Schiller, A Dowlati, JR Brahmer, DH Johnson, A Sandler. 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
https://doi.org/10.1097/JTO.0b013e318265b500 pmid: 23059774
20 JD Patel, MA Socinski, EB Garon, CH Reynolds, DR Spigel, MR Olsen, RC Hermann, RM Jotte, T Beck, DA Richards, SC Guba, J Liu, B Frimodt-Moller, WJ John, CK Obasaju, EJ Pennella, P Bonomi, R Govindan. 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
https://doi.org/10.1200/JCO.2012.47.9626 pmid: 24145346
21 RA Soo, M Loh, TS Mok, SH Ou, BC Cho, WL Yeo, DG Tenen, R Soong. 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
https://doi.org/10.1097/JTO.0b013e3182199c03 pmid: 21532500
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