Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with squamous cell carcinoma of the head and neck (original) (raw)
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Frontiers in Oncology
ObjectiveThe treatment approach of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has long been similar for all patients. Any difference in treatment strategy was only based on existing comorbidities and on preferences of the patient and the treating oncologist. The recent advance obtained with immune therapy and more specifically immune checkpoint blockade (ICB) has been a true game changer. Today, patients and physicians have a choice to omit chemotherapy. In a small subset of patients, ICB induces a very durable disease control. The subgroup of patients in which ICB without chemotherapy would be the preferential approach is still ill-defined. Yet, this evolution marks a major step towards a more personalized medicine in R/M HNSCC.Materials and MethodsIn this paper, we present a retrospective cohort study of a patient population that was treated with ICB in a single center and we analyze potential factors that are associated with outcome and may help to ...
BMC Cancer
Background Immune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model. Methods A single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction. Results 201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 month...
Cancers
To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m2 d1-3 and docetaxel 75 mg/m2 d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in y...
Cancers
Background: We sought to compare patterns of response to immune checkpoint inhibitors (ICI) with respect to clinical and genomic features in a retrospective cohort of patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Methods: One hundred seventeen patients with R/M HNSCC treated with ICI were included in this study. Tumor growth kinetics (TGK) prior to and TGK upon immunotherapy (IO) was available for 49 patients. The TGK ratio (TGKR, the ratio of tumor growth velocity before and upon treatment) was calculated. Hyperprogression (HPD) was defined as TGKR ≥ 2. Results: HPD was documented in 18 patients (15.4% of the whole cohort). Patients with HPD had statistically significant shorter progression free survival (PFS) (median PFS 1.8 months (95% CI, 1.03–2.69) vs. 6.1 months for patients with non-HPD (95% CI, 4.78–7.47), p = 0.0001) and overall survival (OS) (median OS 6.53 months (95% CI, 0–13.39) vs. 15 months in patients with non HPD (95% CI, 7....
Atypical patterns of responses in the era of immune checkpoint inhibitors in head and neck cancer
Oral Oncology, 2020
The discovery and implementation into everyday clinical practice of immune checkpoint inhibitors (ICIs) has marked a therapeutic renaissance in the treatment of advanced solid tumors. In head and neck cancer, nivolumab and pembrolizumab have both been approved for recurrent/metastatic disease based on robust clinical activity observed in landmark phase III clinical trials. Despite tremendous improvements in overall survival, patterns of response and progression to ICIs may be distinct from those traditionally described with classical chemotherapy or molecularly targeted therapies. In this context, pseudoprogression is observed in patients treated with ICIs that show response after a transient increase in tumor burden and hyperprogression is described as rapid radiological or clinical progression after immunotherapy. Most importantly, the assessment of radiological response in patients receiving ICIs needs to be differentiated. In this review, we aim to describe radiologic criteria for immune response evaluation and illustrate the newly reported concepts of atypical patterns of response to ICIs.
With an increased understanding of the tumor biology of squamous cell carcinoma of the head and neck (SCCHN), targeted therapies have found their way into the clinical treatment routines against this entity. Nevertheless, to date platinum-based cytostatic agents remain the first line choice and targeting the epidermal growth factor-receptor (EGFR) with combined cetuximab and radiation therapy remains the only targeted therapy approved in the curative setting. Investigation of immune checkpoint inhibitors (ICI), such as antibodies targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, resulted in a change of paradigms in oncology and in the first approval of new drugs for treating SCCHN. Nivolumab and pembrolizumab, two anti-PD-1 antibodies, were the first agents shown to improve overall survival for patients with metastatic/recurrent tumors in recent years. Currently, several clinical trials investigate the role of ICI in different therapeutic settings. A robust set of biomarkers will be an inevitable tool for future individualized treatment approaches including radiation dose de-escalation and escalation strategies. This review aims to summarize achieved goals, the current status and future perspectives regarding targeted therapies and ICI in the management of SCCHN.
Treatment strategy after the discontinuation of immunotherapy for head and neck cancer: a review
Journal of Cancer Metastasis and Treatment, 2023
First-line systemic therapy with immune checkpoint inhibitors (ICIs) is currently the mainstream treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) that is not amenable to local therapy. However, the optimal treatment after discontinuation of ICIs is still unknown, and no large-scale analysis has been conducted in R/M SCCHN. In this narrative review, we summarize the treatment strategies available to continue ICI therapy using the currently available treatment modalities. After the administration of ICIs, unlike cytotoxic agents, the following responses are observed: durable response, pseudo-progressive disease, hyper-progressive disease, mixed response, immune-related adverse events (irAEs), and improved sensitivity to subsequent chemotherapy. Some patients show a durable response to ICIs and a good prognosis; however, many patients will require salvage therapy. We need to select the subsequent treatment according to the various responses unique to ICIs to obtain a durable response. For instance, there are reports on the effectiveness of reapplication of local therapy for a mixed response, retreatment with ICIs, and off-treatment in responsive cases complicated by irAEs. If a durable response can be maintained with ICI therapy, a long-term prognosis that cannot be obtained with conventional chemotherapy can be achieved.
Checkpoint Inhibitors in Cancer Therapy: Clinical Benefits for Head and Neck Cancers
Cancers
Recently, considerable progress has been achieved in cancer immunotherapy. Targeted immune checkpoint therapies have been established for several forms of cancers, which resulted in a tremendous positive impact on patient survival, even in more advanced tumor stages. With a better understanding of cellular responses to immune checkpoint therapies, it will soon be feasible to find targeted compounds which will make personalized medicine practicable. This is a great opportunity, but it also sets tremendous challenges on both the scientific and clinical aspects. Head and neck tumors evade immune surveillance through various mechanisms. They contain fewer lymphocytes (natural killer cells) than normal tissue with an accumulation of immunosuppressive regulatory T cells. Standard therapies for HNSCC, such as surgery, radiation, and chemotherapy, are becoming more advantageous by targeting immune checkpoints and employing combination therapies. The purpose of this review is to provide an o...