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•More than a dozen phase I/II trials with neoadjuvant ICIs in SCCHN have reported results.•Neoadjuvant single-agent or ICIs in combination do not delay surgery and seem safe.•Most ...trials are using immune-related pathological response criteria despite lack of consensus.•Neoadjuvant immunotherapy in SCCHN may allow for post-ICI treatment de-escalation.
Immune-checkpoint inhibitors (ICIs) have shown to improve survival in the first- and second-line settings of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). In the past two years more than a dozen neoadjuvant IO studies have been reported in SCCHN, demonstrating the feasibility of one or a few doses of single agent or combination ICIs. This approach seems safe with no surgical delays due to toxicity in most of the studies with no new safety signals. Efficacy in terms of pathologic response appears promising both with single-agent ICIs and especially with chemo-IO combinations. The scientific rationale and current clinical evidence of neoadjuvant IO trials in SCCHN will be reviewed, including currently debated aspects such as the methodology for radiological and pathological evaluation as well as types and criteria for biomarker use in this setting. Finally, the future perspective of neoadjuvant IO in SCCHN will be approached.
Head and neck cancer (HNC) is currently the sixth most common solid malignancy, accounting for a 50% five-year mortality rate. In the past decade, substantial improvements in understanding its ...molecular biology have allowed for a growing development of new biomarkers. Among these, the field of liquid biopsy has seen a sustained growth in HNC, demonstrating the feasibility to detect different liquid biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTC), extracellular vesicles and microRNAs. Liquid biopsy has been studied in HPV-negative squamous cell carcinoma of the head and neck (SCCHN) but also in other subentities such as HPV-related SCCHN, EBV-positive nasopharyngeal cancer and oncogene-driven salivary gland cancers. However, future studies should be internally and externally validated, and ideally, clinical trials should incorporate the use of liquid biomarkers as endpoints in order to prospectively demonstrate their role in HNC. A thorough review of the current evidence on liquid biopsy in HNC as well as its prospects will be conducted.
Background
There are still few data on the activity and safety of cetuximab‐based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN).
...Materials and Methods
This was a retrospective study of patients with SCCHN who received cetuximab‐based SCAI after programmed cell death protein 1 or programmed cell death ligand 1(PDL1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression‐free survival (PFS), overall survival (OS), treatment compliance, and toxicity were evaluated.
Results
Between March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximab‐based combinations (3‐weekly cisplatin‐5FU‐cetuximab n = 2, weekly paclitaxel‐cetuximab n = 17, weekly cisplatin‐cetuximab n = 2, weekly carboplatin‐paclitaxel‐cetuximab n = 2). ORR was 56.5% (11 partial response, 2 complete response). DCR was 78.3%. Among 13 objective responders, median best PCTL was −53.5% (range, −30% to −100%). Median OS and PFS were 12 months and 6 months, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, whereas ORR to SCAI achieved 60%. In LCBI‐treated patients, median PFS with LCBI was 8 months and median PFS and OS with SCAI were 7 months and 12 months, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 adverse events (AEs) occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment‐related deaths.
Conclusion
Cetuximab‐based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era.
Implications for Practice
Cetuximab‐based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck (SCCHN) after progression to PD‐1/PD‐L1 inhibitors. Objective response rate was higher than and progression‐free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, well‐tolerated regimens. These observations have implications for current practice because of the limited evidence to date in SCCHN and the scant therapeutic options in this disease and invite to elucidate which may be the best treatment sequence for patients with head and neck cancer in the IO era.
This study explored the safety and efficacy of salvage chemotherapy combined with cetuximab after progression to immune checkpoint inhibitors in patients with recurrent/metastatic squamous cell cancer of the head and neck.
Objective
Clinical guidelines recommend psychological screening in cancer patients. However, most scales cover many items and hamper detection. In addition, patients are generally referred from ...routine consultations. The specific objective of the present study was to develop and validate a tool, Anxiety, Depression, Coping (ADAF), to screen for anxiety and depression and assess coping in cancer patients.
Methods
Cross‐sectional, multicenter study performed in the medical and radiotherapy‐oncology services of five hospitals in Madrid and coordinated by the Medical Oncology Service of Hospital Clínico San Carlos (CEIC nº19/265‐E). To determine psychometric properties, the ADAF screening questionnaire ADAF was administered. ADAF includes five items (1 related to anxiety symptoms, 2 related to depressive symptoms, 1 for helplessness coping, and 1 for avoidance coping). Hospital Anxiety and Depression Scale and Mini‐Mental Adjustment to Cancer scale were used as the gold standards. Intraclass correlation coefficients were calculated and receiver operating characteristic (ROC) curves constructed. A p value of <0.05 was considered significant.
Results
A total of 186 patients completed the evaluation. The correlation coefficients were significant for all dimensions (anxiety, depression, helplessness coping, and avoidance coping) (p < 0.001). The statistical analysis of the ROC curves suggested that the cut‐off point for screening was >2 points (3 in the case of depression), with a sensitivity and specificity between 62% and 90%, and an area under the curve above 0.8 for the first 4 items.
Conclusions
ADAF screening has adequate reliability and good sensitivity and specificity. This instrument is useful and can be easily applied to identify emotional and coping problems in cancer patients.
Coronavirus disease 2019 (COVID‐19) pandemic is affecting a high percentage of the population at an unprecedented rate. Cancer patients comprise a subgroup especially vulnerable to this infection. ...Herein, we present a prospective analysis of epidemiological, clinical, radiological and laboratory data of consecutive adult cancer patients seen in the Clínico San Carlos University Hospital (Madrid, Spain), and admitted to hospital and tested for COVID‐19 between 21 February 2020 and 8 May 2020 due to clinical suspicion of infection. Data from 73 patients with confirmed COVID‐19 and active solid tumors or diagnosed within the previous 5 years were analyzed. The most frequent malignancy was lung cancer (19%) and 54 patients (74%) were on active cancer treatment. Most common findings on presentation included cough (55%), fever (52%) and dyspnea (45%), and 32 (44%) patients showed oxygen saturation levels below 95%. Radiologically, 54 (73%) patients presented an abnormal pattern, the most frequent being infiltrates (64%). 18 (24.7%) patients died in hospital and 55 (75.3%) were discharged with clinical resolution of the event. Multivariable logistic regression adjusted for age and tumor stage showed higher odds of in‐hospital death associated with a history of cardiovascular disease, hospitalization in the previous 30 days, and several features on admission including dyspnea, higher qSOFA score, higher C‐reactive protein levels and an abnormal neutrophil count. We present prospective, real‐world evidence that can help articulate cancer care protocols for patients infected with SARS‐CoV‐2, with special focus on features on admission that can stratify patients with a higher risk of death from COVID‐19.
What's new?
This report provides prospective data about cancer patients with COVID‐19 in a situation of maximum pressure on the healthcare system of a large urban area in Western Europe. Despite a milder clinical profile on presentation, in‐hospital mortality of COVID‐19 was higher in cancer patients than in the general population. The mortality risk was associated with a history of cardiovascular disease and several variables on admission, but seemed not to be influenced by tumor type or anti‐tumor therapy. The evidence could help articulate cancer care protocols for patients infected with SARS‐CoV‐2 and identify patients with a higher risk of in‐hospital death.
Regulatory T cells (Tregs) is a subtype of CD4+ T cells that produce an inhibitory action against effector cells. In the present work we interrogated genomic datasets to explore the transcriptomic ...profile of breast tumors with high expression of Tregs. Only 0.5% of the total transcriptome correlated with the presence of Tregs and only four transcripts, BIRC6, MAP3K2, USP4 and SMG1, were commonly shared among the different breast cancer subtypes. The combination of these genes predicted favorable outcome, and better prognosis in patients treated with checkpoint inhibitors. Twelve up-regulated genes coded for proteins expressed at the cell membrane that included functions related to neutrophil activation and regulation of macrophages. A positive association between MSR1 and CD80 with macrophages in basal-like tumors and between OLR1, ABCA1, ITGAV, CLEC5A and CD80 and macrophages in HER2 positive tumors was observed. Expression of some of the identified genes correlated with favorable outcome and response to checkpoint inhibitors: MSR1, CD80, OLR1, ABCA1, TMEM245, and ATP13A3 predicted outcome to anti PD(L)1 therapies, and MSR1, CD80, OLR1, ANO6, ABCA1, TMEM245, and ATP13A3 to anti CTLA4 therapies, including a subgroup of melanoma treated patients. In this article we provide evidence of genes strongly associated with the presence of Tregs that modulates the response to check point inhibitors.
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