•This ESMO-EURACAN Clinical Practice Guideline provides key recommendations for managing nasopharyngeal cancer (NPC).•It covers screening, clinical and pathological diagnosis, staging and risk ...assessment, treatment and follow-up.•Treatment algorithms for locoregional and recurrent/metastatic NPC are provided.•Recommendations were compiled by the authors based on available scientific data and the authors' collective expert opinion.
Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M ...HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated the efficacy of durvalumab (an anti-PD-L1 monoclonal antibody) or durvalumab plus tremelimumab (an anti-CTLA-4 monoclonal antibody) versus standard of care (SoC) in R/M HNSCC patients.
Patients were randomly assigned to receive 1 : 1 : 1 durvalumab (10 mg/kg every 2 weeks q2w), durvalumab plus tremelimumab (durvalumab 20 mg/kg q4w plus tremelimumab 1 mg/kg q4w × 4, then durvalumab 10 mg/kg q2w), or SoC (cetuximab, a taxane, methotrexate, or a fluoropyrimidine). The primary end points were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary end points included progression-free survival (PFS), objective response rate, and duration of response.
Patients were randomly assigned to receive durvalumab (n = 240), durvalumab plus tremelimumab (n = 247), or SoC (n = 249). No statistically significant improvements in OS were observed for durvalumab versus SoC hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72–1.08; P = 0.20 or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85–1.26; P = 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9–43.1), 30.4% (24.7–36.3), and 30.5% (24.7–36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related adverse events (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively), and anemia (17.5%) for SoC. Grade ≥3 trAE rates were 10.1%, 16.3%, and 24.2% for durvalumab, durvalumab plus tremelimumab, and SoC, respectively.
There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab.
ClinicalTrials.gov: NCT02369874.
•OS was not significantly different for durvalumab or for durvalumab plus tremelimumab compared with SoC.•The study was not designed to assess OS between immunotherapies, but adding tremelimumab did not appear to enhance durvalumab activity.•Failure to meet the primary end point may have been impacted by factors resulting in an unexpectedly long OS for the SoC arm.
Data on preoperative chemotherapy in resectable oral cavity cancer are conflicting. We present the long-term results of a randomized trial of induction chemotherapy in resectable oral cavity cancer.
...A randomized, parallel, multicentre trial evaluated the impact of three cycles of cisplatin 100 mg/m2 and fluorouracil 1000 mg/m2 (120-h infusion administered every 21 days) in stage T2–T4, N0–N2, previously untreated patients with advanced disease. Control group received upfront surgery. Postoperative radiation was offered to both arms when pathologic risk features were identified. The co-primary end points were the occurrence of locoregional or distant tumour relapse, and death.
Among the 198 enrolled patients, with a median follow-up of 11.5 years, there was no difference in the incidence of locoregional relapse between chemotherapy and control group (P = 0.6337), nor in distant metastasis development (P = 0.1527). There was also no difference between groups in overall survival (P = 0.3402). Patients with a pathological complete response (pCR) had higher probability of survival than those without (10-year OS: 76.2% versus 41.3%, P = 0.0004). Late toxicities in patients with a minimum follow-up of 60 months (42 in each group) were similar between arms, except from fibrosis (cumulative incidence 40% versus 22% in chemotherapy arm) and grade 2 dysphagia (14% versus 5%).
Long-term follow-up of this randomized trial confirmed the absence of survival benefit with preoperative chemotherapy in oral cavity cancer. Late toxicity was similar in the two arms except for fibrosis and dysphagia, which were less in the chemotherapy arm. The survival benefit for patients achieving a pCR was maintained.
Abstract Pain in head and neck cancer represents a major issue, before, during and after the oncological treatments. The most frequent cause of pain is chemo/radiation related oral mucositis, which ...involves 80% of the patients and worsens their quality of life inhibiting speaking, eating, drinking or swallowing and sometimes reducing the treatment compliance, the maximum dose intensity and thus the potential efficacy of treatment. Nevertheless pain is still often under estimated and undertreated. An Italian multidisciplinary group of head and neck cancer specialists met with the aim of reaching a consensus on pain management in this setting. The Delphi Appropriateness method was used for the consensus. External expert reviewers evaluated the final statements. The paper contains 30 consensus-reached statements about pain management in HNC patients and offers a review of recent literature in these topics.
The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib—a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit ...in advanced basal cell carcinoma (BCC)—in a patient population representative of clinical practice. Primary analysis data are presented.
Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points.
Evaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0–44) months. Most patients (98%) had ≥1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure ≥12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7–71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6–48.1) in patients with metastatic BCC.
The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control.
NCT01367665.
•Safety consistent with previous experience: TEAEs are tolerable and mostly reversible.•No association between CPK abnormalities and muscle spasm.•Long-term vismodegib not associated with worsening frequency/severity of new TEAEs.•Response rates were 68.5% in locally advanced BCC and 36.9% in metastatic BCC.•Patients with Gorlin syndrome responded better to vismodegib.
Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival ...with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up.
EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140mg/day) or placebo. Final OS and updated safety data are reported.
Minimum follow-up was 42months. Kaplan–Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1months) although the difference did not reach statistical significance stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64–1.12; P=0.24. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation–positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3months for cabozantinib versus 18.9months for placebo HR, 0.60; 95% CI, 0.38–0.94; P=0.03 (not adjusted for multiple subgroup analyses), with corresponding values of 20.2 versus 21.5months (HR, 1.12; 95% CI, 0.70–1.82; P=0.63) in the RET M918T–negative subgroup. Median treatment duration was 10.8months with cabozantinib and 3.4months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis.
The secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T–positive tumors may experience a greater treatment benefit with cabozantinib.
NCT00704730
Salivary duct carcinoma (SDC), an aggressive subtype of salivary gland cancer, is androgen receptor (AR)–positive in 67–96% of cases. In patients with locally recurrent and metastatic (R/M) ...AR-positive SDC, androgen deprivation therapy (ADT) has an overall response rate of 18–64.7%. In this study, we describe the efficacy of adjuvant ADT in patients with poor-risk (stage 4a) AR-positive SDC.
This is a retrospective cohort study in which patients with stage 4a AR-positive SDC were offered adjuvant ADT, i.e. bicalutamide, luteinizing hormone-releasing hormone (LHRH) analogue or a combination of these after tumour resection. In the control group, data were collected on patients with stage 4a SDC who underwent a tumour resection but did not receive adjuvant ADT.
Twenty-two AR-positive SDC patients were treated with adjuvant ADT for a median duration of 12 months. The control group consisted of 111 SDC patients. After a median follow-up of 20 months in the ADT-treated patients and 26 months in the control group, the 3-year disease-free survival (DFS) was estimated as 48.2% (95% confidence interval CI 14.0–82.4%) and 27.7% (95% CI 18.5–36.9%) (P = 0.037). Multivariable Cox regression analysis showed a hazard ratio of 0.138 (95% CI 0.025–0.751, P = 0.022) for DFS and 0.064 (95% CI 0.005–0.764, P = 0.030) for overall survival (OS) in favour of the ADT-treated patients.
Poor-risk, AR-positive SDC patients who received adjuvant ADT have a significantly longer DFS compared with patients in the control group, who did not receive adjuvant ADT. For OS, this was just below and above the significance level, in case there was or was no correction for confounders.
•Salivary duct carcinoma (SDC) is an aggressive subtype of salivary gland cancer.•Palliative androgen deprivation therapy (ADT) has a response rate of 18–64.7%.•In this retrospective cohort study, we describe the efficacy of adjuvant ADT in poor-risk SDC.•Adjuvant ADT showed a significantly longer disease-free survival.•Overall survival was significantly longer after correction for confounders.
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