Abstract
Immune checkpoint inhibition (ICI) has been established as successful modality in cancer treatment. Combination concepts are used to optimize treatment outcome, but may also induce higher toxicity rates than monotherapy. Several rationales support the combination of radiotherapy (RT) with ICI as radioimmunotherapy (RIT), but it is still unknown in which clinical situation RIT would be most beneficial. Therefore, we have conducted a retrospective matched-pair analysis of 201 patients with advanced-stage cancers and formed two groups treated with programmed cell death protein 1 (PD-1) inhibitors only (PD1i) or in combination with local RT (RIT) at our center between 2013 and 2017. We collected baseline characteristics, programmed death ligand 1 (PD-L1) status, mutational status, PD-1 inhibitor and RT treatment details, and side effects according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. Patients received pembrolizumab (n = 93) or nivolumab (n = 108), 153 with additional RT. For overall survival (OS) and progression-free survival (PFS), there was no significant difference between both groups. After propensity score matching (PSM), we analyzed 96 patients, 67 with additional and 29 without RT. We matched for different covariates that could have a possible influence on the treatment outcome. The RIT group displayed a trend towards a longer OS until the PD1i group reached a survival plateau. PD-L1-positive patients, smokers, patients with a BMI ≤ 25, and patients without malignant melanoma showed a longer OS when treated with RIT. Our data show that some subgroups may benefit more from RIT than others. Suitable biomarkers as well as the optimal timing and dosage must be established in order to achieve the best effect on cancer treatment outcome.
Highlights
Immunotherapy (IT) with immune checkpoint inhibitors (ICI) has changed oncologic treatment strategies dramatically even in hard-to-treat advanced cancers like malignant melanoma (MM), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCC), or metastatic urothelial carcinoma [1,2,3,4]
Besides established risk factors associated with shortened survival time, such as the presence of brain metastases and a low performance status, we have investigated other covariates that potentially affect ICI treatment outcome
Our database consisted of 209 patients who were treated with anti-PD-1-antibodies from 2013 to 2017 at the University Hospital of Cologne
Summary
Immunotherapy (IT) with immune checkpoint inhibitors (ICI) has changed oncologic treatment strategies dramatically even in hard-to-treat advanced cancers like malignant melanoma (MM), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCC), or metastatic urothelial carcinoma [1,2,3,4]. Highest response rates including long-term remissions are currently achieved by ICI combinations such as the anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Antibody ipilimumab with a programmed cell death protein 1 (PD-1) inhibitor [5,6]. Due to significantly increased immune-related adverse events (IrAE), alternative approaches that enhance antitumor responses but spare IrAE are urgently needed and topic of intensive research efforts. One promising approach that enhances antitumor immune response while sparing toxicity might be the combination of ICI with local radiotherapy (RT) [7,8,9]. RT-induced systemic immunological effects have been discussed for a long time. Local application of RT to the tumor induces effects that go beyond the killing of tumor cells at that exact site and send distinct signals to the host’s immune system
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