Combining Immunotherapy with Multikinase Inhibitors: A Cautious New Promise

Raja Pramanik; Atul Sharma; Akash Kumar

doi:10.4103/ijmpo.ijmpo_326_20

Indian Journal of Medical and Paediatric Oncology, Table of Contents

CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(06): 901-905
DOI: 10.4103/ijmpo.ijmpo_326_20

Courting Controversy

Combining Immunotherapy with Multikinase Inhibitors: A Cautious New Promise

Raja Pramanik

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

,

Atul Sharma

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

,

Akash Kumar

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

› Author Affiliations

Abstract

Immune check point inhibitors have made a sea change in oncology practice in current times. These drugs have crossed the conventional boundaries of histology and organ of origin. Tumor agnostic approvals for mismatch repair deficient, microsatellite-instability (MSI)-H and recently tumor mutational burden-high solid tumors have been a giant leap. The Oncology community seems poised to embrace the concept of “immunotherapy for all.” Recent studies have evaluated the manipulation of tumor-associated macrophages using multi-kinase inhibitors, to make even MSI low tumor responsive to checkpoint inhibitors. With accelerated food and drug administration approvals, the promise of this combo is palpable but definitely merits caution.

Keywords

Immune checkpoint inhibitors - lenvatinib - regorafenib

Full Text

References

References
1 Rates of Progression-Free Survival in MSI-H/dMMR Metastatic Colorectal Cancer Doubled by Pembrolizumab The ASCO Post. Available from: https://www.ascopost.com/issues/july-10-2020-supplement-conference-highlights-asco20-virtual-scientific-program/rates-of-progression-free-survival-in-msi-hdmmr-metastatic-colorectal-cancer-doubled-bypembrolizumab/. [Last accessed on 2020 Jul 08].
2 Research C for DE and. FDA Approves Pembrolizumab for First-Line Treatment of MSI-H/dMMR Colorectal Cancer. FDA; 2020. Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-first-line-treatment-msi-hdmmr-colorectal-cancer. [Last accessed on 2020 Jul 08].
3 Research C for DE and. FDA Approves Pembrolizumab for Adults and Children with TMB-H Solid Tumors. FDA; 2020. Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors. [Last accessed on 2020 Jul 08].
4 Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D. et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019; 380: 1116-27
5 Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT. et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019; 380: 1103-15
6 Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M. et al. Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: An open-label, dose-escalation, and dose-expansion phase Ib trial (REGONIVO, EPOC1603). J Clin Oncol 2020; 38: 2053-61
7 Kato Y, Tabata K, Kimura T, Yachie-Kinoshita A, Ozawa Y, Yamada K. et al. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+T cells through reduction of tumor-associated macrophage and activation of the interferon pathway. PLoS One 2019; 14: e0212513
8 Kawazoe A, Fukuoka S, Nakamura Y, Kuboki Y, Mikamoto Y, Shima H. et al. An open-label phase II study of lenvatinib plus pembrolizumab in patients with advanced gastric cancer (EPOC1706). J Clin Oncol 2020; 38 Suppl 4: 374-4
9 Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, Shia J, Segal NH. et al. Immunotherapy in colorectal cancer: Rationale, challenges and potential. Nat Rev Gastroenterol Hepatol 2019; 16: 361-75
10 Chen LT, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC. et al. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer 2020; 23: 510-9
11 Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M. et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol 2018; 4: e180013
12 Ratti M, Lampis A, Hahne JC, Passalacqua R, Valeri N. Microsatellite instability in gastric cancer: Molecular bases, clinical perspectives, and new treatment approaches. Cell Mol Life Sci 2018; 75: 4151-62
13 Li J, Qin S, Xu R, Yau TC, Ma B, Pan H. et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16: 619-29
14 Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M. et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Lond Engl 2013; 381: 303-12
15 Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA. et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): An open-label, multicentre, phase 2 study. Lancet Oncol 2017; 18: 1182-91
16 Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK. et al. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol 2016; 34: 2728-35
17 Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J. et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: An interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2019; 20: 711-8
18 Research C for DE and. Simultaneous Review Decisions for Pembrolizumab Plus Lenvatinib in Australia, Canada andUS. FDA; 2019. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/simultaneous-review-decisions-pembrolizumab-plus-lenvatinib- australia- canada-and-us. [Last acessed on 2020 Jul 08].
19 Khair DO, Bax HJ, Mele S, Crescioli S, Pellizzari G, Khiabany A, et al. Combining immune checkpoint inhibitors: Established and emerging targets and strategies to improve outcomes in melanoma. Front Immunol. 2019 Mar 19;10:453. doi: 10.3389/fimmu.2019.00453. PMID: 30941125; PMCID: PMC6435047
20 Patil VM, Noronha V, Joshi A, Abhyankar A, Menon N, Banavali S. et al.. Low doses in immunotherapy: Are they effective? Cancer Res Stat Treat 2019; 2: 54
21 Yoo SH, Keam B, Keam M, Kim SH, Kim YJ, Kim TM. Low-dose nivolumab can be effective in non-small cell lung cancer: Alternative option for financial toxicity. ESMO Open 2018; 3: e000332
22 Renner A, Burotto M, Rojas C. Immune checkpoint inhibitor dosing: Can we go lower without compromising clinical efficacy? J Glob Oncol. 2019 Jul;5:1-5. doi: 10.1200/JGO.19.00142. PMID: 31348737; PMCID: PMC6690659
23 Search of: Cabozantinib Nivolumab List Results – Clinical Trials. Available from: https://clinicaltrials.gov/ct2/results?term=cabozantinib+nivolumab. [Last accessed on 2020 Jul 08].
24 Search of: Pembrolizumab Regorafenib List Results ClinicalTrials. Available from: https://clinicaltrials.gov/ct2/results?cond=&term=pembrolizumab+regorafenib&cntry=&state=&city=&dist. [Last accessed on 2020 Jul 08].
25 Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J. et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys 2013; 86: 343-9
26 Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR. et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 2014; 124: 687-95
27 Nivolumab and Ipilimumab and Radiation Therapy in MSS and MSI High Colorectal and Pancreatic Cancer Full Text View – Clinical Trials Available from: https://clinicaltrials.gov/ct2/show/NCT03104439. [Last accessed on 2020 Aug 09]