Patients with platinum-refractory head and neck cancer had significantly longer survival with nivolumab treatment than with standard, single-agent therapy. Response rates were also higher and quality ...of life maintained longer with nivolumab.
Squamous-cell carcinoma of the head and neck is a major cause of cancer-associated illness and death, with more than 600,000 cases diagnosed annually worldwide.
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Most patients present with locoregionally advanced disease, and more than 50% have recurrence within 3 years.
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Patients with squamous-cell carcinoma of the head and neck who have cancer progression within 6 months after platinum-based chemotherapy administered in the context of primary or recurrent disease have a median survival of 6 months or less.
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No therapeutic options prolong survival among these patients.
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The recurrence and metastasis of squamous-cell carcinoma of the head and neck are . . .
PURPOSE OF REVIEWThe aim of this review is to summarize the current knowledge on the genomic characterization of squamous cell carcinomas of the head and neck (HNSCC) and discusses how these ...abnormalities could be incorporated into a therapeutic approach.
RECENT FINDINGSTobacco and HPV infection, the two main risk factors of HNSCC, allow the definition of two groups with distinct anatomoclinical and genetic features. As tobacco and HPV infection are not exclusive, exposure to both risk factors is associated with an intermediate prognostic. HPV-positive, nontobacco-related HNSCCs are associated with a better prognosis, a rather more simple genomic profile, frequent activating mutations of genes involved in pi3kinase pathway, and the very low incidence of mutations of tumor suppressor genes. HPV-negative, tobacco-related HNSCC are genetically more complex. HPV-negative HNSCC are characterized by almost mandatory inactivating mutations/deletions of tumor suppressor genes (especially TP53 and CDKN2A) and the occurrence, though less frequent, of activating mutations or amplifications of some oncogenes that encode for cell cycle proteins or receptors with tyrosine kinase activity. Despite many efforts to improve therapeutic targeting in RM HNSCC, Cetuximab, a monoclonal antibody targeting REGF, remains the sole approved targeted treatment in RM HNSCC.
SUMMARYDespite the increasingly precise genomic characterization of HNSCCs, precision medicine is struggling to find its place in the management of HNSCCs. Inclusion of enriched populations in dedicated trials is likely to help implement precision medicine in the management of HNSCCs.
Summary Background Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment ...options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy. Methods In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2 per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov , number NCT01345682. Findings Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6·7 months (IQR 3·1–9·0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2·6 months 95% CI 2·0–2·7 for the afatinib group vs 1·7 months 1·5–2·4 for the methotrexate group; hazard ratio HR 0·80 95% CI 0·65–0·98, p=0·030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 10% of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 9% vs three 2%), stomatitis (20 6% vs 13 8%), fatigue (18 6% vs five 3%), and neutropenia (1 <1% vs 11 7%); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients. Interpretation Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. Funding Boehringer Ingelheim.
PURPOSE OF REVIEWCheckpoint inhibitors (CPI) are revolutionizing the treatment of advanced cancers including recurrent and or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN).
...RECENT FINDINGSIn this review, we will summarize the results of prospective trials evaluating CPI and particularly antiprogrammed death 1 (PD-1)/antiprogrammed death-ligand 1 (PD-L1) in RM-SCCHN.
SUMMARYNivolumab and Pembrolizumab, two anti-PD-1 CPI, were associated with longer overall survival than standard chemotherapy in pretreated RM-SCCHN in two randomized phase 3 trials (respectively CHECKMATE-141 and KEYNOTE-040). Both are now approved in this setting. In the KEYNOTE-048 trial, the pembrolizumab was also associated with a longer survival when compared with the EXTREME regimen in first-line RM-SCCHN patients whose tumors overexpressed PD-L1 (combined positive score ≥20%). This trial also showed a superiority of platinum-based chemotherapy and pembrolizumab vs. EXTREME regimen in unselected first-line RM-SCCHN. Pembrolizumab will probably be the next standard of care for first-line RM-SCCHN with high expression of PD-L1. Further evaluation of CPI combined with other antitumoral agents is ongoing in advanced and locally advanced SCCHN.
PURPOSE OF REVIEWNasopharyngeal carcinoma prognosis is related to its potential locoregional invasion and metastatic spread. Among prognostic factors, initial tumor-node-metastasis stage is the main ...one, besides other biological parameters. Worldwide development of positron emission tomography imaging is changing modalities of staging. Concomitant chemoradiotherapy represents one of the most recent advances in the treatment of nasopharyngeal carcinoma patients, besides intensity-modulated radiation therapy. This review updates these recent advances in diagnosis and treatment of nasopharyngeal carcinoma.
RECENT FINDINGSRecent publications have shown the superiority of fused positron emission tomography/computed tomography over positron emission tomography alone and conventional imaging to do an accurate staging and to impact on patient management. Circulating Epstein–Barr virus DNA load may be a useful prognostic marker in endemic regions. Recent meta-analysis confirmed the superiority of concurrent chemoradiotherapy to radiotherapy alone. Previous publications have shown that induction chemotherapy with new agents might be promising. Data demonstrating targeted therapies efficacy in metastatic nasopharyngeal carcinoma are limited to date.
SUMMARYPositron emission tomography-computed tomography is replacing conventional imaging in the initial M staging of nasopharyngeal carcinoma. Its usefulness in response evaluation after therapy and its place in the follow-up need to be prospectively evaluated. Cisplatin-based concomitant chemoradiotherapy is now the standard treatment for locally advanced patients. However, incidence of relapses remains high, and new multimodal therapy is needed.
Worldwide, head and neck carcinomas account for 5% of all malignancies. Two-thirds of patients relapse after initial multimodal therapy. Until early 2010, the median overall survival (OS) of ...metastatic patients was about 10 months.
New drugs have been incorporated in patient management, thus enabling an increase in OS. Several first and second line protocols are now available but the lack of direct comparison makes the choice difficult between them.
This work aims to define the comprehensive medical management of patients with relapsing head and neck carcinoma. In September 2020, the French head and neck groups GORTEC, Unicancer head and Neck group, GROCC and GETTEC decided to promote a one-day meeting to propose how to incorporate these new regimens in first and second line treatment for recurrent and metastatic head and neck cancer (R/M SCCHNC). Twelve French medical oncologist involved in the management of R/M SCCHNC for more than 10 years examined the literature and proposed a simple and practical management based on five criteria: age, delay from last platinum injection, combined positive score expression level, FIT or UNFIT patient according to physician decision, fast response needed or not.
Background
Response patterns with immune checkpoint inhibitors may be different from those with chemotherapy. Therefore, assessment of response to immunotherapy with the Response Evaluation Criteria ...in Solid Tumors (RECIST), version 1.1, could result in premature treatment termination. The randomized, open‐label, phase 3 CheckMate 141 trial (NCT02105636), which evaluated nivolumab in recurrent/metastatic squamous cell carcinoma of the head and neck after platinum therapy, allowed treatment beyond first RECIST‐defined progression (TBP) according to protocol‐specified criteria.
Methods
In CheckMate 141, patients with RECIST‐defined progression who had a stable performance status and demonstrated clinical benefit without rapid disease progression were permitted to receive TBP with nivolumab at 3 mg/kg every 2 weeks until further progression, which was defined as an additional ≥10% increase in tumor volume. This post hoc analysis evaluated outcomes for patients who received TBP with nivolumab.
Results
Of 240 patients randomized to nivolumab, 146 experienced RECIST‐defined progression. Sixty‐two of these patients received TBP, and 84 discontinued treatment (no TBP). Among the 60 TBP patients evaluable for response, 15 (25%) had no change in their tumor burden, and 15 (25%) had reductions in target lesion size; 3 patients (5%) had reductions >30%. The median overall survival among TBP patients was 12.7 months (95% confidence interval, 9.7‐14.6 months). No new safety signals were observed with TBP. Exploratory analyses of immune cell biomarkers suggested a potential relationship with initial and TBP responses.
Conclusions
Tumor burden reduction was noted in a proportion of patients who received TBP with nivolumab in CheckMate 141. Additional research is warranted to identify factors predictive of a TBP benefit in this population.
In the randomized, open‐label, phase 3 CheckMate 141 trial in patients with recurrent/metastatic squamous cell carcinoma of the head and neck after platinum therapy, patients with a stable performance status and the potential for clinical benefit were permitted to receive treatment beyond first Response Evaluation Criteria in Solid Tumors–defined progression (TBP) with nivolumab; tumor burden reduction was noted in a proportion of these patients. Additional research is warranted to identify factors predictive of benefit with TBP in this population.
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