The clinical added value of the addition of anti-CTL-4 to anti-PD-1 alone is questionable and clearly increasing toxicity regarding pivotal studies in the treatment of melanoma and renal carcinoma
- 88 Downloads
In recent years, we have witnessed undeniable progress in the treatment of cancer, leading to increased survival of metastatic patients as part of what is considered an incremental progress. The advances that have contributed to it include the development of immunotherapies, like anti-PD-1 and anti-CTL-4 treatments, and the introduction of tyrosine kinase inhibitors (TKi) .
Combining drugs of the same class or of different therapeutic classes is a classic strategy in the development of chemotherapy regimens and is recognized in various recommendations. However, we should carefully examine the robustness of evidence, in particular when the combined regimen is associated with a clearly demonstrated increase in toxicity, as is the case for the anti-PD-1/anti-CTL-4 immunotherapy combination .
Even though there is a pre-clinical rationale for combining anti-PD-1 and anti-CTL-4 therapeutics , the interest of introducing such a combination into clinical practice has to...
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interests.
- 3.Intlekofer AM, Craig BT (2013) At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol 94(1: juillet):2539Google Scholar
- 4.Schnipper LE, Davidson NE, Wollins DS, Blayney DW, Dicker AP, Ganz PA, Hoverman JR, Langdon R, Lyman GH, Meropol NJ, Mulvey T, Newcomer L, Peppercorn J, Polite B, Raghavan D, Rossi G, Saltz L, Schrag D, Smith TJ, Yu PP, Hudis CA, Vose JM, Schilsky RL (2016) Updating the American Society of Clinical Oncology value framework: revisions and reflections in response to comments received. J Clin Oncol 34(24):292534CrossRefGoogle Scholar
- 5.Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF, Smylie M, Dummer R, Hill A, Hogg D, Haanen J, Carlino MS, Bechter O, Maio M, Marquez-Rodas I, Guidoboni M, McArthur G, Lebbé C, Ascierto PA, Long GV, Cebon J, Sosman J, Postow MA, Callahan MK, Walker D, Rollin L, Bhore R, Hodi FS, Larkin J (2017) Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 377(14):1345–1356CrossRefGoogle Scholar
- 6.The French National Authority for Health (HAS) (2017) Transparency Commission CT15561_OPDIVO_PIC_EI_association_Yervoy_melanome_Avis2_CT15561.pdf. https://www.has-sante.fr/portail/upload/docs/evamed/CT-15561_OPDIVO_PIC_EI_association_Yervoy_melanome_Avis2_CT15561.pdf. [the easiest access to this source is via the URL]
- 7.Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B, CheckMate 214 Investigators (2018) Nivolumab plus Ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378(14):1277–1290CrossRefGoogle Scholar
- 8.European Medicines Agency Committe for Medicinal Products for Human Use-London (2018) EMA/CHMP/457661/2018 Opinion of the committee for medicinal products for human use on a type II variation to the terms of the marketing authorisation. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/002213/WC500252687.pdf. [the easiest access to this source is via the URL]
- 9.Hellman MD, Ciuleanu T, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O’Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L (2018) Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 378(22):2093–2104CrossRefGoogle Scholar
- 11.Legifrance (2018) Avis relatif aux prix de spécialités pharmaceutiques publiés en application de l’article L. 162-16-6 du code de la sécurité sociale. https://www.legifrance.gouv.fr/affichTexte.do?cidTexte=JORFTEXT000034183611&categorieLien=id