Impact of previous anti-angiogenesis treatment in nivolumab-treated advanced non-small cell lung cancer

Abstract

Aim: To investigate how previous systemic therapy such as anti-angiogenesis can influence cancer immunotherapy for non-small cell lung cancer (NSCLC).

Methods: A total of 134 patients with advanced NSCLC who were treated with nivolumab were retrospectively reviewed. Correlation between status of prior anti-angiogenesis treatment and clinical characteristics were determined. Impact of prior anti-angiogenesis on therapeutic outcome of nivolumab was investigated for tumor efficacy such as progression-free survival (PFS).

Results: Sixteen patients were treated with at least one anti-angiogenesis agent prior to nivolumab. The prior use of anti-angiogenesis agent was associated with stage IV disease, non-squamous histology, and two or more lines of systemic therapy. Median PFS was significantly shorter in the prior anti-angiogenesis group than in no prior anti-angiogenesis group (8.3 vs. 11.3 weeks, log-rank P = 0.006). Multivariate analyses demonstrated that only prior anti-angiogenesis status was associated with worse PFS. There is also a slight trend for worse disease control rate (P = 0.101, Fisher’s exact test) and overall survival (P = 0.200, log-rank) in prior anti-angiogenesis group.

Conclusion: This retrospective study suggests that prior anti-angiogenesis treatment negatively impacts the therapeutic outcome of immunotherapy in advanced NSCLC.

Keywords

Non-small cell lung cancer / nivolumab / angiogenesis / immunotherapy

References

[1] Mok TS,Thongprasert S,Chu DT,Sunpaweravong P,Margono B,Nishiwaki Y,Yang JJ,Jiang H,Watkins CL,Fukuoka M.Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma..N Engl J Med2009;361:947-57

[2] Zhou C,Chen G,Liu XQ,Zhang S,Zhou S,Lu S,Hu C,Luo Y,Ye M,Zhi X,Xiu Q,Zhang L.Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study..Lancet Oncol2011;12:735-42

[3] Solomon BJ,Kim DW,Nakagawa K,Felip E,Paolini J,Iyer S,Wilner KD,Blackhall F.First-line crizotinib versus chemotherapy in ALK-positive lung cancer..N Engl J Med2014;371:2167-77

[4] Shaw AT,Crinò L,Kiura K,Novello S,Gautschi O,Nishio M,Spigel DR,Zheng C,Urban P,Viraswami-Appanna K.Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial..Lancet Oncol2017;18:874-86

[5] Brahmer J,Baas P,Eberhardt WE,Antonia S,Vokes EE,Waterhouse D,Gainor J,Havel L,Garassino MC,Domine M,Reck M,Harbison CT,Spigel DR.Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer..N Engl J Med2015;373:123-35 PMCID:PMC4681400

[6] Borghaei H,Horn L,Steins M,Chow LQ,Felip E,Barlesi F,Arrieta O,Fayette J,Poddubskaya E,Gettinger SN,Rizvi N,Blumenschein GRJr,Dorange C,Graf Finckenstein F.Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer..N Engl J Med2015;373:1627-39 PMCID:PMC5705936

[7] Reck M,Robinson AG,Csőszi T,Gottfried M,Tafreshi A,O'Brien M,Hotta K,Lubiniecki GM,Rangwala R.Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer..N Engl J Med2016;375:1823-33

[8] Carbone DP,Paz-Ares L,Horn L,Felip E,Ciuleanu TE,Ready N,Nair S,Peters S,Wrangle JM,Borghaei H,Villaruz LC,Krejci J,Chang H,Bhagavatheeswaran P,Socinski MA.First-line nivolumab in stage IV or recurrent non-small-cell lung cancer..N Engl J Med2017;376:2415-26

[9] Robert C,Brady B,Maio M,Hassel JC,McNeil C,Savage KJ,Lebbé C,Mihalcioiu C,Mauch C,Arance A,Schadendorf D,Lundgren-Eriksson L,Sharkey B,Atkinson V.Nivolumab in previously untreated melanoma without BRAF mutation..N Engl J Med2015;372:320-30

[10] Ning YM,Maher VE,Tang S,Palmby T,Liu Q,Kim G.FDA approval summary: atezolizumab for the treatment of patients with progressive advanced urothelial carcinoma after platinum-containing chemotherapy..Oncologist2017;22:743-9 PMCID:PMC5469588

[11] Motzer RJ,McDermott DF,Hammers HJ,Tykodi SS,Procopio G,Castellano D,Gurney H,Bono P,Gauler TC,Tomita Y,Kollmannsberger C,Ravaud A,Xu LA,Sharma P.Nivolumab versus everolimus in advanced renal-cell carcinoma..N Engl J Med2015;373:1803-13 PMCID:PMC5719487

[12] Cancer stat facts: lung and bronchus cancer. Surveillance, epidemiology, and end results. National Cancer Institute. Available from: https://seer.cancer.gov/statfacts/html/lungb.html [Last accessed on 10 Jan 2018]

[13] Five-year survival rate for nivolumab-treated advanced lung cancer patients much higher than historical rate. AACR Annual Meeting; 2017 April 1-5, Washington, USA. Available from: http://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1031#.WVFpd-srLIU [Last accessed on 10 Jan 2018]

[14] Sandler A,Perry MC,Schiller JH,Lilenbaum R.Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer..N Engl J Med2006;355:2542-50

[15] Highlights of prescribing information. AVASTIN® (bevacizumab). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125085s225lbl.pdf [Last accessed on 10 Jan 2018]

[16] Manegold C,Gray JE,Nicolson M,Reck M,Brustugun OT,Felip E,Garrido P,Marabelle A,Mornex F,Papotti M,Smit EF,van Meerbeeck JP,Chih-Hsin Yang J,Vokes E.The Potential of combined immunotherapy and antiangiogenesis for the synergistic treatment of advanced NSCLC..J Thorac Oncol2017;12:194-207

[17] Mancuso MR,Norberg SM,Sennino B,Yao VJ,Brooks P,Shalinsky DR,McDonald DM.Rapid vascular regrowth in tumors after reversal of VEGF inhibition..J Clin Invest2006;116:2610-21 PMCID:1578604

[18] Ribatti D.Tumor refractoriness to anti-VEGF therapy..Oncotarget2016;7:46668-77 PMCID:PMC5216828

[19] Langer CJ,Borghaei H,Patnaik A,Gentzler RD,Stevenson JP,Panwalkar A,Gubens M,Awad MM,Ge Y,Gandhi L.Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study..Lancet Oncol2016;17:1497-508

[20] Highlights of prescribing information. NEXAVAR® (sorafenib). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021923s008s009lbl.pdf [Last accessed on 10 Jan 2018]

[21] Highlights of prescribing information. SUTENT® (sunitinib malate). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021938s13s17s18lbl.pdf [Last accessed on 10 Jan 2018]

[22] Highlights of prescribing information. VOTRIENT® (pazopanib). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022465s-010S-012lbl.pdf [Last accessed on 10 Jan 2018]

[23] Highlights of prescribing information. INLYTA® (axitinib). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202324lbl.pdf [Last accessed on 10 Jan 2018]

[24] Highlights of prescribing information. CYRAMZA® (ramucirumab).Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477s007lbl.pdf [Last accessed on 10 Jan 2018]

[25] Highlights of prescribing information. ZALTRAP® (ziv-aflibercept).Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125418s000lbl.pdf [Last accessed on 10 Jan 2018]

[26] Johnson DH,Novotny WF,Nemunaitis JJ,Langer CJ,Gaudreault J,Holmgren E.Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer..J Clin Oncol2004;22:2184-91

[27] Scagliotti G,von Pawel J,Pereira JR,Abrão Miziara JE,De Marinis F,Arén O,Albert I,Grossi F,Cupit L,Dimatteo S.Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer..J Clin Oncol2010;28:1835-42

[28] Ebos JM,Cruz-Munoz W,Christensen JG.Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis..Cancer Cell2009;15:232-9 PMCID:PMC4540346

[29] Shojaei F,Lee JH,Christensen JG.HGF/c-Met pathway is one of the mediators of sunitinib-induced tumor cell type-dependent metastasis..Cancer Lett2012;320:48-55

[30] Ebos JM,Christensen JG,Kerbel RS.Multiple circulating proangiogenic factors inducedby sunitinib malate are tumor-independent and correlate with antitumor efficacy..Proc Natl Acad Sci U S A2007;104:17069-74 PMCID:PMC2040401

[31] Lu KV,Parachoniak CA,Aghi MK,Isachenko N,Phillips JJ,Park M.VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex..Cancer Cell2012;22:21-35 PMCID:PMC4068350

[32] Grothey A,Purdie DM,Sargent D,Kozloff M.Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE)..J Clin Oncol2008;26:5326-34

[33] Schmittnaegel M,Kadioglu E,Wyser Rmili C,Kienast Y,Ooi CH,De Palma M.Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade..Sci Transl Med2017;9:eaak9670

[34] Allen E,Rivera LB,Missiaen R,Feyen K,Hanahan D,Bergers G.Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation..Sci Transl Med2017;9:eaak9679

[35] Kanda S,Shiraishi H,Tanaka A,Sunami K,Mizugaki H,Fujiwara Y,Yamamoto N,Tamura T.Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study..Ann Oncol2016;27:2242-50 PMCID:PMC5178141

[36] Zhu J,Gray SW,Weeks JC.Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer..JAMA2012;307:1593-601 PMCID:PMC3418968

[37] Chamberlain MC.Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: a retrospective case series..J Neurooncol2017;133:561-9

[38] Kobari Y,Takagi T,Nakazawa H.Rapid progressive disease after nivolumab therapy in three patients with metastatic renal cell carcinoma..In Vivo2017;31:769-71 PMCID:PMC5566938