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Immune Checkpoint Inhibitors as Switch or Continuation Maintenance Therapy in Solid Tumors: Rationale and Current State

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Abstract

First-line chemotherapy for many solid tumors is limited by toxicity. There is a growing interest in maintenance therapy as a strategy for prolonging the benefits of first-line therapy while minimizing toxicity. Maintenance therapy can comprise either continuation of an agent given as part of the first-line regimen (continuation maintenance) or treatment with a new agent (switch maintenance). Maintenance therapy is already established in several solid tumors, including lung, breast, gastric, colorectal, and ovarian cancer. Immune checkpoint inhibitor treatment has been shown to prolong duration of response and overall survival, but efficacy is generally restricted to a limited proportion of patients with selected tumors. Thus, efforts are ongoing to determine whether the clinical benefits of immune checkpoint inhibitors can be extended using novel treatment schedules and settings, including maintenance therapy. Early- and late-phase clinical trials have investigated the efficacy and safety of immune checkpoint inhibitors as switch and continuation maintenance in different tumors, and a range of phase III trials are ongoing. Interpretation of results requires consideration of trial designs, eligibility criteria, and primary endpoints, in addition to biomarker exploration, and assessment of quality of life and cost effectiveness. Findings from ongoing trials will help further define the role of immune checkpoint inhibitors as maintenance therapy across a spectrum of solid tumors.

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References

  1. Clarke G, Johnston S, Corrie P, et al. Withdrawal of anticancer therapy in advanced disease: a systematic literature review. BMC Cancer. 2015;15:892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lee JE, Chung CU. Update on the evidence regarding maintenance therapy. Tuberc Respir Dis (Seoul). 2014;76:1–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Agarwala AK, Hanna NH. Advanced non-small cell lung cancer: the role of maintenance therapy. Ther Adv Med Oncol. 2010;2:17–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Eren OO, Ozturk MA, Sonmez OU, Oyan B. Safety, feasibility, and efficacy of capecitabine maintenance in patients with advanced gastric cancer: a retrospective study. Am J Ther. 2016;23:e1493–7.

    Article  PubMed  Google Scholar 

  5. Yeh J, Marrone KA, Forde PM. Neoadjuvant and consolidation immuno-oncology therapy in stage III non-small cell lung cancer. J Thorac Dis. 2018;10:S451–9.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Thatcher N, Heighway J. Maintenance and consolidation therapy in patients with unresectable stage III/IV non-small cell lung cancer. Oncologist. 2010;15:1034–42.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Polo V, Besse B. Maintenance strategies in stage IV non-small-cell lung cancer (NSCLC): in which patients, with which drugs? Ann Oncol. 2014;25:1283–93.

    Article  CAS  PubMed  Google Scholar 

  8. Gerber DE, Schiller JH. Maintenance chemotherapy for advanced non-small-cell lung cancer: new life for an old idea. J Clin Oncol. 2013;31:1009–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tonini G, Imperatori M, Vincenzi B, et al. Rechallenge therapy and treatment holiday: different strategies in management of metastatic colorectal cancer. J Exp Clin Cancer Res. 2013;32:92.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Bookman MA. The addition of new drugs to standard therapy in the first-line treatment of ovarian cancer. Ann Oncol. 2010;21(Suppl. 7):vii211–7.

    PubMed  Google Scholar 

  11. Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007;7:573–84.

    Article  CAS  PubMed  Google Scholar 

  12. Chen HH, Chen WC, Liang ZD, et al. Targeting drug transport mechanisms for improving platinum-based cancer chemotherapy. Expert Opin Ther Targets. 2015;19:1307–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Grivas PD, Daignault S, Tagawa ST, et al. Double-blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma. Cancer. 2014;120:692–701.

    Article  CAS  PubMed  Google Scholar 

  14. Ciuleanu T, Brodowicz T, Zielinski C, et al. 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;374:1432–40.

    Article  CAS  PubMed  Google Scholar 

  15. Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1274–84.

    Article  CAS  PubMed  Google Scholar 

  16. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375:2154–64.

    Article  CAS  PubMed  Google Scholar 

  17. Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:1949–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379:2495–505.

    Article  CAS  PubMed  Google Scholar 

  19. Paz-Ares L, de Marinis F, Dediu M, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012;13:247–55.

    Article  CAS  PubMed  Google Scholar 

  20. Paz-Ares LG, de Marinis F, Dediu M, et al. 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;31:2895–902.

    Article  CAS  PubMed  Google Scholar 

  21. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–50.

    Article  CAS  PubMed  Google Scholar 

  22. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–92.

    Article  CAS  PubMed  Google Scholar 

  23. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.

    Article  CAS  PubMed  Google Scholar 

  24. Coleman RL, Brady MF, Herzog TJ, et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18:779–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012;30:2039–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Aghajanian C, Goff B, Nycum LR, et al. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015;139:10–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  CAS  PubMed  Google Scholar 

  28. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25:1539–44.

    Article  CAS  PubMed  Google Scholar 

  29. Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013;14:29–37.

    Article  CAS  PubMed  Google Scholar 

  30. Luo HY, Li YH, Wang W, et al. Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety. Ann Oncol. 2016;27:1074–81.

    Article  CAS  PubMed  Google Scholar 

  31. Goey KKH, Elias SG, van Tinteren H, et al. Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 study. Ann Oncol. 2017;28:2128–34.

    Article  CAS  PubMed  Google Scholar 

  32. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.

    Article  PubMed  Google Scholar 

  33. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–75.

    Article  CAS  PubMed  Google Scholar 

  34. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.

    Article  CAS  PubMed  Google Scholar 

  35. Gridelli C, de Marinis F, Pujol JL, et al. Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexed versus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2012;7(11):1713–21.

    Article  CAS  PubMed  Google Scholar 

  36. Oza AM, Matulonis UA, Malander S, et al. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2018;19:1117–25.

    Article  PubMed  Google Scholar 

  37. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  38. Balar AV, Weber JS. PD-1 and PD-L1 antibodies in cancer: current status and future directions. Cancer Immunol Immunother. 2017;66:551–64.

    Article  CAS  PubMed  Google Scholar 

  39. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387:1909–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Galsky MD, Saci A, Szabo PM, et al. Impact of tumor mutation burden on nivolumab efficacy in second-line urothelial carcinoma patients: exploratory analysis of the phase II checkmate 275 study. Ann Oncol. 2017;28(Suppl. 5):abstract 848PD.

  41. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18:312–22.

    Article  CAS  PubMed  Google Scholar 

  42. Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res. 2015;3:436–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hato SV, Khong A, de Vries IJ, Lesterhuis WJ. Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics. Clin Cancer Res. 2014;20:2831–7.

    Article  CAS  PubMed  Google Scholar 

  44. Pol J, Vacchelli E, Aranda F, et al. Trial Watch: immunogenic cell death inducers for anticancer chemotherapy. Oncoimmunology. 2015;4:e1008866.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Bezu L, Gomes-de-Silva LC, Dewitte H, et al. Combinatorial strategies for the induction of immunogenic cell death. Front Immunol. 2015;6:187.

    PubMed  PubMed Central  Google Scholar 

  46. Zitvogel L, Apetoh L, Ghiringhelli F, et al. The anticancer immune response: indispensable for therapeutic success? J Clin Invest. 2008;118:1991–2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kyi C, Postow MA. Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges. Immunotherapy. 2016;8:821–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity. 2013;39:74–88.

    Article  CAS  PubMed  Google Scholar 

  49. Pfirschke C, Engblom C, Rickelt S, et al. Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity. 2016;44:343–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lu YC, Robbins PF. Cancer immunotherapy targeting neoantigens. Semin Immunol. 2016;28:22–7.

    Article  CAS  PubMed  Google Scholar 

  51. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Brown JS, Sundar R, Lopez J. Combining DNA damaging therapeutics with immunotherapy: more haste, less speed. Br J Cancer. 2018;118:312–24.

    Article  CAS  PubMed  Google Scholar 

  53. McConkey DJ, Choi W, Ochoa A, Dinney CPN. Intrinsic subtypes and bladder cancer metastasis. Asian J Urol. 2016;3:260–7.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Choi W, Porten S, Kim S, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014;25:152–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Grivas P, Emamekhoo H, Elson P, et al. PD1, PDL1, PDL2 tumor tissue (TT) expression as predictors of response to neoadjuvant chemotherapy (NAC) and outcome in bladder cancer (BC). J Clin Oncol. 2016;34:abstract e16023.

    Article  Google Scholar 

  56. Luo M, Fu L. The effect of chemotherapy on programmed cell death 1/programmed cell death 1 ligand axis: some chemotherapeutical drugs may finally work through immune response. Oncotarget. 2016;7:29794–803.

    PubMed  PubMed Central  Google Scholar 

  57. Rojko L, Reiniger L, Teglasi V, et al. Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients. J Cancer Res Clin Oncol. 2018;144:1219–26.

    Article  CAS  PubMed  Google Scholar 

  58. Song Z, Yu X, Zhang Y. Altered expression of programmed death-ligand 1 after neo-adjuvant chemotherapy in patients with lung squamous cell carcinoma. Lung Cancer. 2016;99:166–71.

    Article  PubMed  Google Scholar 

  59. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70.

    Article  CAS  PubMed  Google Scholar 

  60. Lynch TJ, Bondarenko I, Luft A, et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012;30:2046–54.

    Article  CAS  PubMed  Google Scholar 

  61. Govindan R, Szczesna A, Ahn MJ, et al. Phase III trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer. J Clin Oncol. 2017;35:3449–57.

    Article  CAS  PubMed  Google Scholar 

  62. Galsky MD, Wang H, Hahn NM, et al. Phase 2 trial of gemcitabine, cisplatin, plus ipilimumab in patients with metastatic urothelial cancer and impact of DNA damage response gene mutations on outcomes. Eur Urol. 2018;73:751–9.

    Article  CAS  PubMed  Google Scholar 

  63. Wei XX, Lundgren K, Teo MY, Rosenberg JE. First-line PD-1/PD-L1 inhibitor followed by carboplatin (carbo)-based chemotherapy (chemo) or the reverse sequence in cisplatin-ineligible metastatic urothelial cancer (mUC) patients (pts). J Clin Oncol. 2018;36:abstract e16517.

    Article  Google Scholar 

  64. Bang YJ, Cho JY, Kim YH, et al. Efficacy of sequential ipilimumab monotherapy versus best supportive care for unresectable locally advanced/metastatic gastric or gastroesophageal junction cancer. Clin Cancer Res. 2017;23:5671–8.

    Article  CAS  PubMed  Google Scholar 

  65. Chung HC, Arkenau HT, Lee J, et al. Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019;7:30.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Galsky MD, Pal SK, Mortazavi A, et al. Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients (pts) with metastatic urothelial cancer (mUC): HCRN GU14-182. J Clin Oncol. 2019;37:abstract 4504.

    Article  Google Scholar 

  67. Kok M, Voorwerk L, Horlings H, et al. Adaptive phase II randomized trial of nivolumab after induction treatment in triple negative breast cancer (TONIC trial): final response data stage I and first translational data. J Clin Oncol. 2018;36:abstract 1012.

    Article  Google Scholar 

  68. Charalambous H, Kyriacou F, Stylianou I, et al. Switch maintenance pembrolizumab in patients with metastatic non-small cell lung cancer (SWIPE). J Thorac Oncol. 2018;13(10):abstract P1.01-12.

  69. Gadgeel SM, Ventimiglia J, Kalemkerian GP, et al. Phase II study of maintenance pembrolizumab (pembro) in extensive stage small cell lung cancer (ES-SCLC) patients (pts). J Clin Oncol. 2017;35:abstract 8504.

    Article  Google Scholar 

  70. Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379:2342–50.

    Article  CAS  PubMed  Google Scholar 

  71. Durm GA, Althouse SK, Sadiq AA, et al. Phase II trial of concurrent chemoradiation with consolidation pembrolizumab in patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179. J Clin Oncol. 2018;36:abstract 8500.

    Article  Google Scholar 

  72. Ready N, Owonikoko TK, Postmus PE, et al. CheckMate 451: a randomized, double-blind, phase III trial of nivolumab (nivo), nivo plus ipilimumab (ipi), or placebo as maintenance therapy in patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC) after first-line platinum-based doublet chemotherapy (PT-DC). J Clin Oncol. 2016;34:abstract TPS8579.

    Article  Google Scholar 

  73. Bristol-Myers Squibb announces CheckMate-451 study did not meet primary endpoint of overall survival with opdivo plus yervoy vs. placebo as a maintenance therapy in patients with extensive-stage small cell lung cancer after completion of first-line platinum based chemotherapy. 26 November, 2018. Available from: https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-checkmate-451-study-did-not-mee. Accessed 24 Aug 2019.

  74. Ledermann J, Fujiwara K, Oza AM. Phase 3 trial of avelumab (anti-PD-L1) in combination with and/or following platinum-based chemotherapy in patients with untreated ovarian cancer. Int J Gynecol Cancer. 2016;26(Suppl. 3):abstract 753.

  75. Merck KGaA, Darmstadt, Germany and Pfizer provide update on JAVELIN Ovarian 100 trial of avelumab in previously untreated advanced ovarian cancer. 21 December, 2018. Available from: https://www.emdgroup.com/en/news/javelin-ovarian-100-21-12-2018.html. Accessed 24 Aug 2019.

  76. Moehler MH, Ryu M, Lee K, et al. JAVELIN Gastric 100: phase 3 trial of avelumab (anti-PD-L1) maintenance therapy versus continuation of first-line chemotherapy in patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC). J Clin Oncol. 2018;36:abstract TPS195.

    Article  Google Scholar 

  77. Powles T, Grivas P, Aragon-Ching JB, et al. A multicentre, international, randomised, open-label phase 3 trial of avelumab + best supportive care (BSC) vs BSC alone as maintenance therapy after first-line platinum-based chemotherapy in patients with advanced urothelial cancer (JAVELIN Bladder 100). Ann Oncol. 2016;27(Suppl. 6):abstract 842TiP.

  78. Gerber DE, Urbanic JJ, Langer CJ, et al. Randomized phase III trial of concurrent chemoradiation followed by nivolumab or placebo for locally advanced non-small cell lung cancer (NSCLC) (RTOG 3505). J Clin Oncol.2017;35:abstract TPS8579.

    Article  Google Scholar 

  79. Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378:2078–92.

    Article  CAS  PubMed  Google Scholar 

  80. Capuzzo F, Mccleod MJ, Hussein M, et al. IMpower130: progression-free survival (PFS) and safety analysis from a randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC. Ann Oncol. 2018;29 (Suppl. 8):abstract LBA53.

  81. Papadimitrakopoulou VA, Cobo M, Bordoni R, et al. IMpower132: PFS and safety results with 1L atezolizumab + carboplatin/cisplatin + pemetrexed in stage IV non-squamous NSCLC. J Thorac Oncol. 2018;13(10):abstract OA05.07.

  82. Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378:2288–301.

    Article  CAS  PubMed  Google Scholar 

  83. Socinski MA, Jotte RM, Cappuzzo F, et al. Overall survival analysis of IMpower150, a randomized phase 3 study of atezolizumab + chemotherapy ± bevacizumab vs chemo + bev in 1L nonsquamous NSCLC. J Clin Oncol. 2018;36:abstract 9002.

  84. Jotte RM, Cappuzzo F, Vynnychenko I, Socinski MA. IMpower131: primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. J Clin Oncol. 2018;36:abstract LBA9000.

    Article  Google Scholar 

  85. Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379:2040–51.

    Article  CAS  PubMed  Google Scholar 

  86. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378:2093–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Borghaei H, Hellmann MD, Paz-Ares LG, et al. Nivolumab + platinum-doublet chemotherapy vs chemotherapy as first-line treatment for advanced non-small cell lung cancer with tumor PD-L1 expression: results from CheckMate 227. J Clin Oncol. 2018;36:9001.

    Article  Google Scholar 

  88. Bristol-Myers Squibb provides update on Part 2 of CheckMate-227. 24 July, 2019. Available from: https://news.bms.com/press-release/rd-news/bristol-myers-squibb-provides-update-part-2-checkmate-227. Accessed 24 Aug 2019.

  89. Horn L, Mansfield AS, Reck M, et al. Phase I/III trial of atezolizumab with carboplatin and etoposide in ES-SCLC in first-line setting (IMpower133). J Clin Oncol. 2017;35:abstract TPS8584.

    Article  Google Scholar 

  90. Horn L, Mansfield AS, Szczesna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220–9.

    Article  CAS  PubMed  Google Scholar 

  91. Mok T, Johnson M, Garon E, et al. POSEIDON: a phase 3 study of first-line durvalumab ± tremelimumab + chemotherapy vs chemotherapy alone in metastatic NSCLC. J Thorac Oncol. 2017;12(11):abstract P1.04-008.

  92. Nakagawa K, Yang JC, Park K, et al. Checkmate 722: a phase 3 trial of nivolumab with chemotherapy or ipilimumab vs chemotherapy in epidermal growth factor receptor (EGFR)-mutation, T790 M-negative stage IV or recurrent non-small cell lung cancer (NSCLC) after EGFR tyrosine kinase inhibitor (TKI) therapy. Ann Oncol. 2016;27(Suppl. 9):abstract 481TiP.

  93. Lee NY, Ferris J, Beck JT, et al. JAVELIN Head and Neck 100: a phase 3 trial of avelumab in combination with chemoradiotherapy (CRT) vs CRT for 1st-line treatment of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). J Clin Oncol. 2017;35:abstract TPS6093.

    Article  Google Scholar 

  94. Freidlin B, Little RF, Korn EL. Design issues in randomized clinical trials of maintenance therapies. J Natl Cancer Inst. 2015;107(11):djv225.

    Article  PubMed  PubMed Central  Google Scholar 

  95. European Medicines Agency. Guideline on the evaluation of anticancer medicinal products in man. 13 December, 2012. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/01/WC500137128.pdf. Accessed 24 Aug 2019.

  96. Dimopoulos MA, Petrucci MT, Foa R, et al. Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of “progression-free survival 2” as a clinical trial end-point. Haematologica. 2015;100:e328–30.

    PubMed  PubMed Central  Google Scholar 

  97. Oronsky B, Carter CA, Reid TR, et al. Confirmatory trials in the evaluation of anticancer medicinal products in man–PFS2: a measure of therapeutic action-at-a-distance. Neoplasia. 2015;17:716–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Pilz LR, Manegold C, Schmid-Bindert G. Statistical considerations and endpoints for clinical lung cancer studies: can progression free survival (PFS) substitute overall survival (OS) as a valid endpoint in clinical trials for advanced non-small-cell lung cancer? Transl Lung Cancer Res. 2012;1:26–35.

    PubMed  PubMed Central  Google Scholar 

  99. Adams SV, Ceballos R, Newcomb PA. Quality of life and mortality of long-term colorectal cancer survivors in the Seattle colorectal cancer family registry. PLoS ONE. 2016;11:e0156534.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Van Cutsem E, Falcone A, Garcia-Carbonero R, et al. Proxies of quality of life in metastatic colorectal cancer: analyses in the RECOURSE trial. ESMO Open. 2017;2:e000261.

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, Division of Oncology, University of Washington, Seattle Cancer Care Alliance, 825 Eastlake Ave E, Seattle, WA, 98109, USA

    Petros Grivas

  2. Arizona Oncology (US Oncology Network), University of Arizona, Creighton University, Phoenix, AZ, USA

    Bradley J. Monk

  3. Department of Urology, Yale University School of Medicine, New Haven, CT, USA

    Daniel Petrylak

  4. Department of Thoracic Oncology, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Lung Clinic Grosshansdorf, Grosshansdorf, Germany

    Martin Reck

  5. Pfizer Ltd., Tadworth, UK

    Grace Foley

  6. Merck KGaA, Darmstadt, Germany

    Silke Guenther

  7. EMD Serono, Rockland, MA, USA

    Dan Hennessy

  8. Pfizer Inc., New York, NY, USA

    Constantin Makris

  9. Johannes-Gutenberg University, University Medical Center, Mainz, Germany

    Markus Moehler

Authors
  1. Petros Grivas
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  2. Bradley J. Monk
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  3. Daniel Petrylak
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  4. Martin Reck
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  5. Grace Foley
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  6. Silke Guenther
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  7. Dan Hennessy
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  8. Constantin Makris
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  9. Markus Moehler
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Corresponding author

Correspondence to Petros Grivas.

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Funding

Medical writing support for this review was provided by ClinicalThinking and funded by Merck KGaA and Pfizer, Inc.

Conflict of interest

Petros Grivas reports a consulting/advisory role for AstraZeneca, Bayer, Biocept, Bristol-Myers Squibb, Clovis Oncology, Dendreon, Driver Inc., EMD Serono, Exelixis, Foundation Medicine, Genentech, Genzyme, Heron Therapeutics, Janssen, Merck & Co., Mirati Therapeutics, Pfizer, QED Therapeutics, and Seattle Genetics; a speaker’s role (educational, unbranded program) for Bristol-Myers Squibb and Genentech; travel support from AstraZeneca and Clovis Oncology; and institutional research funding (for clinical trials) from AstraZeneca, Bavarian Nordic, Bayer, Bristol-Myers Squibb, Clovis Oncology, Debiopharm, Genentech, Immunomedics, Merck & Co., Mirati Therapeutics, Oncogenex, and Pfizer. Bradley Monk reports a consulting/advisory role for Advaxis, Aravive, Geistlich, Genmab, ImmunoGen, Mateon, Merck, Myriad, Perthera, Pfizer, Takeda, and VBL Therapeutics; and a speaker’s role for AstraZeneca, Clovis, Janssen/Johnson & Johnson, Roche/Genentech, and TESARO Incorporated. Daniel Petrylak reports a consulting/advisory role for Bayer, Bellicum, Dendreon, Sanofi, Johnson & Johnson, Exelixis, Ferring, Millennium, Medivation, Pfizer, Roche, and Tyme Pharmaceuticals; research funding from Agenysis, Celgene, Dendreon, Eli Lilly, Johnson & Johnson, Millineum, Oncogenix, Progenics, Roche, and Sanofi; and expert testimony for Sanofi. Martin Reck reports a consulting/advisory role for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck, Merck Sharpe & Dohme, Novartis, Pfizer, and Roche; and a speaker’s role for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck, Merck Sharpe & Dohme, Novartis, Pfizer, and Roche. Grace Foley and Constantin Makris are employed by Pfizer Inc. Silke Guenther is employed by Merck KGaA. Dan Hennessy is employed by EMD Serono (a business of Merck KGaA). Markus Moehler reports a consulting/advisory role for Amgen, Bayer, Bristol-Myers Squibb, Eli Lilly, Merck, Merck Sharpe & Dohme, Onyx, Pfizer, and Roche; research funding from AIO-Studien-gGmbH, Amgen, Bristol-Myers Squibb, European Organisation for Research and Treatment of Cancer, Merck, Merck Sharp & Dohme, Roche, Taiho Pharmaceutical, and Transgene; and honoraria from American Society of Clinical Oncology, Amgen, Bristol-Myers Squibb, Eli Lilly, European Society for Medical Oncology, Falk, Merck, Nordic, and Pfizer.

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Grivas, P., Monk, B.J., Petrylak, D. et al. Immune Checkpoint Inhibitors as Switch or Continuation Maintenance Therapy in Solid Tumors: Rationale and Current State. Targ Oncol 14, 505–525 (2019). https://doi.org/10.1007/s11523-019-00665-1

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