Chemotherapy plus single/double immunotherapy in the treatment of non-oncogene addicted advanced non-small cell lung cancer: where do we stand and where are we going?

References

• Kazandjian D, Suzman DL, Blumenthal G, et al. FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Oncologist. 2016;21(5):634–642.
   PubMed Web of Science ®Google Scholar
• Pai-Scherf L, Blumenthal GM, Li H, et al. FDA approval summary: pembrolizumab for treatment of metastatic non-small cell lung cancer: first-line therapy and beyond. Oncologist. 2017;22(11):1392–1399.
   PubMed Web of Science ®Google Scholar
• Weinstock C, Khozin S, Suzman D, et al. U.S. Food and drug administration approval summary: atezolizumab for metastatic non–small cell lung cancer. Clin Cancer Res. 2017 August 15;23(16):4534–4539.
   PubMed Web of Science ®Google Scholar
• Weiss GJ. A new era of treating advanced lung cancer is upon us. Transl Lung Cancer Res. 2018;7(Suppl 3):S202–S205.
   PubMedGoogle Scholar
• Vaddepally RK, Kharel P, Pandey R, et al. Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence. Cancers (Basel). 2020;12(3):738.
   PubMed Web of Science ®Google Scholar
• Shields MD, Marin-Acevedo JA, Pellini B. Immunotherapy for advanced non–small cell lung cancer: a decade of progress. Am Soc Clin Oncol Educat Book. 2021 May 13;41(41):e105–e127.
   Google Scholar
• Steuer CE, Ramalingam SS. Advances in immunotherapy and implications for current practice in non–small-cell lung cancer. JCO Oncol Pract. 2021;17:662–668.
   PubMedGoogle Scholar
• Deng H, Zhou C. From CheckMate 227 to CheckMate 9LA: rethinking the status of chemotherapy in the immunotherapy era-chemo-free or chemo-reform?. Transl Lung Cancer Res. 2021;10(4):1924–1927.
   PubMed Web of Science ®Google Scholar
• FDA approves cemiplimab-rwlc for patients with NSCLC and high PD-L1 Expression Ascopost.com [internet]. [cited 2021 Oct]. Available from: https://ascopost.com/issues/march-25-2021/fda-approves-cemiplimab-rwlc-for-patients-with-nsclc-and-high-pd-l1-expression
   Google Scholar
• Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018 May 31;378(22):2078–2092. Epub 2018 Apr 16. PMID: 29658856.
   PubMed Web of Science ®Google Scholar
• Rodríguez-Abreu D, Powell SF, Hochmair MJ, et al. Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Ann Oncol. 2021 Jul;32(7):881–895. Epub 2021 Apr 22. PMID: 33894335.
   PubMed Web of Science ®Google Scholar
• Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2040–2051. Epub 2018 Sep 25. PMID: 30280635.
   PubMed Web of Science ®Google Scholar
• Robinson AG, Vicente D, Tafreshi A, et al. First-line pembrolizumab plus chemotherapy for patients with advanced squamous NSCLC: 3-year follow-up from KEYNOTE-407. Eur Lung Cancer Virtual Congr. 2021;16(suppl_4):S748–S802;25-27 March.
   Google Scholar
• Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018 Jun 14;378(24):2288–2301. Epub 2018 Jun 4. PMID: 29863955.
   PubMed Web of Science ®Google Scholar
• Socinski MA, Nishio M, Jotte RM, et al. IMpower150 final overall survival analyses for atezolizumab plus bevacizumab and chemotherapy in first-line metastatic nonsquamous NSCLC. J Thorac Oncol. 2021 Jul 24;S1556-0864(21):2322–2324. Epub ahead of print. PMID: 34311108.
   Google Scholar
• West H, McCleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Jul;20(7):924–937. Epub 2019 May 20. PMID: 31122901.
   PubMed Web of Science ®Google Scholar
• Gogishvili M, Melkadze T, Makharadze T, et al. LBA51 - EMPOWER-Lung 3: cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC). Ann Oncol. 2021;32(suppl_5):S1283–S1346.
   Web of Science ®Google Scholar
• Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):198–211. Epub 2021 Jan 18. Erratum in: Lancet Oncol. 2021 Mar;22(3):e92. PMID: 33476593.
   PubMed Web of Science ®Google Scholar
• Reck M, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: checkMate 9LA 2-year update. Esmo Open. 2021 October 01;6(5):100273.
   PubMed Web of Science ®Google Scholar
• Phase III POSEIDON trial shows positive results for patients taking chemotherapy plus durvalumab and tremelimumab. Iaslc.com [internet] [cited 2021 Oct]. Available from: https://www.iaslc.org/iaslc-news/press-release/phase-iii-poseidon-trial-shows-positive-results-patients-taking
   Google Scholar
• Efficacy comparison of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy in participants with metastatic non-squamous non-small cell lung cancer (NSCLC); Clinicaltrial.gov [Internet]. [cited 2021 Oct]. Available from: https://clinicaltrials.gov/ct2/show/NCT04581824?term=NCT04581824&draw=2&rank=1;
   Google Scholar
• A study of Tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin versus pembrolizumab plus pemetrexed and carboplatin/cisplatin in participants with previously untreated advanced non-squamous non-small cell lung cancer (SKYSCRAPER-06); Clinical trials.gov [Internet]. [cited 2021 Oct]. Available from: https://clinicaltrials.gov/ct2/show/NCT04619797?term=NCT04619797&draw=2&rank=1;
   Google Scholar
• Nivolumab and ipilimumab in combination with immunogenic chemotherapy for patients with advanced NSCLC (NSCLC); Clinical trials.gov [Internet] [cited 2021 Oct]. Available from: https://clinicaltrials.gov/ct2/show/NCT04043195?term=NCT04043195&draw=2&rank=1
   Google Scholar
• Phase II clinical trial of NIVO-IPI-TAXANE in untreated metastatic NSCLC (TOP1705); Clinical trials.gov [Internet] [cited 2021 Oct]. Available from: https://clinicaltrials.gov/ct2/show/NCT03573947?term=NCT03573947&draw=2&rank=1;
   Google Scholar
• Phase I/II study of nivolumab and ipilimumab combined with nintedanib in non small cell lung cancer; Clinical trials.gov [Internet] [cited 2021 Oct]. Available from: https://clinicaltrials.gov/ct2/show/NCT03377023?term=NCT03377023&draw=2&rank=1;
   Google Scholar
• A study of TSR-022 in participants with advanced solid tumors (AMBER); Clinical trials.gov [Internet] [ cited 2021 October[. Available from: https://clinicaltrials.gov/ct2/show/NCT02817633?term=NCT02817633&draw=2&rank=1
   Google Scholar
• Jiang P, Mao Z, Wang Q, et al. An indirect comparison between Nivolumab + Ipilimumab + Two Cycles of Chemotherapy vs. Pembrolizumab + Chemotherapy as first-line treatment for metastatic non-small cell lung cancer. Front Oncol. 2021;11:698199. Published 2021 Sep 13.
   PubMed Web of Science ®Google Scholar
• Roundtable discussion: borghaei discusses combination therapies in NSCLC with high TMB [Internet] [cited 2021 Dec]. Available from: https://www.targetedonc.com/view/roundtable-discussion-borghaei-discusses-combination-therapies-in-nsclc-with-high-tmb
   Google Scholar
• Spigel looks at using different regimens depending on PD-L1 status in NSCLC [Internet] [cited 2021 Dec]. Available from: https://www.targetedonc.com/view/spigel-looks-at-using-different-regimens-depending-on-pd-l1-status-in-nsclc
   Google Scholar
• Lazzari C, Karachaliou N, Bulotta A, et al. Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer?. Ther Adv Med Oncol. 2018;10:1758835918762094. Published 2018 Apr 6.
   Web of Science ®Google Scholar
• Rassy E, Bakouny Z, Assi T, et al. The interaction of immune checkpoint inhibitor plus chemotherapy in non-small-cell lung cancer: subadditivity, additivity or synergism?. Immunotherapy. 2019 Jul;11(10):913–920. Epub 2019 Jun 12. PMID: 31188048.
   PubMed Web of Science ®Google Scholar
• Bailly C, Thuru X, Quesnel B. Combined cytotoxic chemotherapy and immunotherapy of cancer: modern times. NAR Cancer. 2020;2(1):zcaa002. Published 2020 Feb 17.
   PubMedGoogle Scholar
• Ramakrishnan R, Gabrilovich DI. Mechanism of synergistic effect of chemotherapy and immunotherapy of cancer. Cancer Immunol Immunother. 2011 Mar;60(3):419–423. Epub 2010 Oct 26. PMID: 20976448.
   PubMed Web of Science ®Google Scholar
• Apetoh L, Ladoire S, Coukos G, et al. Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?. Ann Oncol. 2015 Sep;26(9):1813–1823. Epub 2015 Apr 28. PMID: 25922066.
   PubMed Web of Science ®Google Scholar
• Pavan A, Attili I, Pasello G, et al. Immunotherapy in small-cell lung cancer: from molecular promises to clinical challenges. J Immunother Cancer. 2019;7(1):205.
   PubMed Web of Science ®Google Scholar
• Wang C, Kulkarni P, Salgia R. Combined checkpoint inhibition and chemotherapy: new era of 1st-line treatment for non-small-cell lung cancer. Mol Ther Oncolytics. 2019;13:1–6. Published 2019 Mar 19.
   PubMed Web of Science ®Google Scholar
• Zhu HH, Feng Y, Hu XS. Emerging immunotherapy targets in lung cancer. Chin Med J (Engl). 2020;133(20):2456–2465.
   PubMed Web of Science ®Google Scholar
• Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and Anti-CTLA-4 therapies in cancer: mechanisms of action, efficacy, and limitations. Front Oncol. 2018;8:86. Published 2018 Mar 28.
   PubMed Web of Science ®Google Scholar
• Mooradian MJ, Gainor JF. Putting the brakes on CTLA-4 inhibition in lung cancer?. Transl Lung Cancer Res. 2018;7(Suppl 1):S35–S38.
   PubMedGoogle Scholar
• Liebler DC, Holzer TR, Haragan A, et al. Analysis of immune checkpoint drug targets and tumor proteotypes in non-small cell lung cancer. Sci Rep. 2020;10:9805.
   PubMed Web of Science ®Google Scholar
• Passiglia F, Reale ML, Cetoretta V, et al. Immune-checkpoint inhibitors combinations in metastatic NSCLC: new options on the horizon?. Immunotargets Ther. 2021;10:9–26. Published 2021 Feb 5.
   PubMed Web of Science ®Google Scholar
• Rocco D, Gregorc V, Della Gravara L, et al. New immunotherapeutic drugs in advanced non-small cell lung cancer (NSCLC): from preclinical to phase I clinical trials. Expert Opin Investig Drugs. 2020 Sep;29(9):1005–1023. Epub 2020 Jul 21. PMID: 32643447.
   PubMed Web of Science ®Google Scholar
• Tagliamento M, Bironzo P, Novello S. New emerging targets in cancer immunotherapy: the role of Vista. ESMO Open. 2020;4(Suppl 3):e000683.
   PubMedGoogle Scholar
• Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98–106.
   PubMed Web of Science ®Google Scholar
• Rocco D, Gravara LD, Gridelli C. The new immunotherapy combinations in the treatment of advanced non-small cell lung cancer: reality and perspectives. Curr Clin Pharmacol. 2020;15(1):11–19.
   PubMed Web of Science ®Google Scholar
• Mathew M, Safyan RA, Shu CA. PD-L1 as a biomarker in NSCLC: challenges and future directions. Ann Transl Med. 2017;5(18):375.
   PubMed Web of Science ®Google Scholar
• Davis AA, Patel VG. The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. J Immunother Cancer. 2019;7(1):278.
   PubMed Web of Science ®Google Scholar
• Lei Y, Li X, Huang Q, et al. Progress and challenges of predictive biomarkers for immune checkpoint blockade. Front Oncol. 2021;11:617335. Published 2021 Mar 11.
   PubMed Web of Science ®Google Scholar
• Friedlaender A, Addeo A, Banna G. New emerging targets in cancer immunotherapy: the role of TIM3. ESMO Open. 2019;4(Suppl 3):e000497.
   PubMedGoogle Scholar
• Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2):e000957.
   PubMed Web of Science ®Google Scholar
• Acharya N, Sabatos-Peyton C, Anderson AC. Tim-3 finds its place in the cancer immunotherapy landscape. J Immunother Cancer. 2020;8(1):e000911.
   PubMed Web of Science ®Google Scholar
• Blons H, Garinet S, Laurent-Puig P, et al. Molecular markers and prediction of response to immunotherapy in non-small cell lung cancer, an update. J Thorac Dis. 2019;11(Suppl 1):S25–S36.
   PubMedGoogle Scholar
• Liberini V, Mariniello A, Righi L, et al. NSCLC biomarkers to predict response to immunotherapy with checkpoint inhibitors (ICI): from the cells to in vivo images. Cancers (Basel). 2021;13(18):4543.
   PubMed Web of Science ®Google Scholar
• Horvath L, Thienpont B, Zhao L, et al. Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook. Mol Cancer. 2020;19(1):141.
   PubMed Web of Science ®Google Scholar
• Pitt JM, Marabelle A, Eggermont A, et al. Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol. 2016 Aug;27(8):1482–1492. Epub 2016 Apr 10. PMID: 27069014.
   PubMed Web of Science ®Google Scholar
• Petitprez F, Meylan M, de Reyniès A, et al. The tumor microenvironment in the response to immune checkpoint blockade therapies. Front Immunol. 2020;11:784. Published 2020 May 7.
   PubMed Web of Science ®Google Scholar
• Tang T, Huang X, Zhang G, et al. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduct Target Ther. 2021;6(1):72.
   PubMed Web of Science ®Google Scholar
• Clarke JM, Wang XF, Gu L, et al. Interim results from the OPTIMAL trial: a phase II clinical trial of combination nivolumab, ipilimumab, and taxane in patients with untreated metastatic non-small cell lung cancer (NSCLC). J Clin Oncol. Published online 2020 May 25;38(15_suppl):e21683–e21683.
   Google Scholar