Open accessPosition article and guidelinesurnal foImmunoTherapy of CancerSociety for Immunotherapy of Cancer(SITC)consensus definitions for resistanceto combinations of immune checkpointinhibitors with targeted therapiesMichael B Atkins Paolo A Ascierto ,2 David Feltquate,3 James L GulleyDouglas B Johnson,5 Nikhil I Khushalani,5 Jeffrey Sosman,?Timonthy A Yap,8Harriet KlugerRyan J Sullivan ,10 Hussein TawbiTo cite:Atkins MB,Ascierto PAABSTRACTprogression or recurrence may occur evenFeltquate D,efal.SocietyImmunotherapy offers deep and durable disease controlafter periods of extended disease controlfor Immunotherapy of Cancerto some patients,but many tumors do not respond(SITC)consensus definitions for(ie,secondary resistance).Previously,theto treatment with single-agent immune checkpointresistance to combinations ofSociety for Immunotherapy of Cancer(SITC)immune checkpoint inhibitorsinhibitors (ICIs).One strategy to enhance responsesdeveloped consensus definitions for clin-with targeted therapies.Joumalto immunotherapy is via combinations with signalfor ImmunoTherapy of Cancertransduction inhibitors,such as antiangiogenic therapies,ical phenotypes of resistance to single-agent202311:e005923.dot:10.1136/which not only directly target cancer cells but alsocheckpoint blockade for therapies targetingjtc-2022-005923could potentially favorably modulate the tumor immuneprogrammed cell death protein 1 and itsmicroenvironment.Combination strategies with ICIs haveligand (PD-1 and PD-L1).3 The definitionsAdditional supplementaldemonstrated enhanced antitumor activity comparedidentified minimum drug exposure require-material is published online only.with tumor-targeted or antiangiogenic therapy alone inments,best response,and requirements forTo view,please visit the joumalrandomized trials in a variety of solid tumor settings,confirmatory scans to define primary resis-online (http://dx.doi.org/10.leading to regulatory approval from the US Food and Drug1136/tc-2022-0059231.tance,secondary resistance,and diseaseAdministration and agencies in other countries for theprogression after discontinuation of therapytreatment of endometrial cancer,kidney cancer,melanoma.Accepted 31 October 2022and hepatocellular carcinoma.Despite improved survivalto support standardized study enrolmentand response rates for some patients when antiangiogeniccriteria and facilitate appropriate compari-or targeted therapies are administered with ICls,manysons in post-anti-PD-(L)1 clinical trials.Thepatients continue to progress after combination treatmentSITC-defined resistance phenotypes forand urgently need new strategies to address thismonotherapy have been shown to be associ-manifestation of resistance to immunotherapy.Previouslyated with distinct clinical factors includingthe Society for Immunotherapy of Cancer (SITC)publishedtumor burden,tumor growth,likelihood toconsensus definitions for resistance to single-agent anti-receive further systemic therapy,and postpro-PD-(L)1.To provide
