Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit (original) (raw)
Related papers
Randomized Phase III Trial of Neoadjuvant Chemotherapy in Head and Neck Cancer: 10-Year Follow-Up
JNCI Journal of the National Cancer Institute, 2004
In 1986, we initiated a multicenter, randomized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) with locoregional treatment alone in patients with head and neck squamous cell carcinoma. Here we report the longterm results of the trial. A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were randomly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment (group A) or locoregional treatment alone (group B). Among all patients, overall survival at 5 and 10 years was 23% (95% confidence interval [CI] ؍ 15.3% to 30.9%) and 19% (95% CI ؍ 11.6% to 26.4%), respectively, for those in group A and 16% (95% CI ؍ 9.6% to 23.4%) and 9% (95% CI ؍ 3.5% to 14.7%), respectively, for those in group B (P ؍ .13). Among operable patients, we observed no difference between group A and group B in overall survival at 5 and 10 years (group A, 31% [95% CI ؍ 14.9% to 47.3%] and 22.7% [95% CI ؍ 7.1% to 38.3%], respectively; group B, 43.3% [95% CI ؍ 25.6% to 61.0%]
Prolonged Survival with Anti Egfr Therapy in Head and Neck Squamous Cell Carcinoma a Case Series
2018
Head and Neck Cancer (HNC) is the sixth most common cancer worldwide, with about 650,000 patients newly diagnosed annually. In the late 1990s, surgery followed by postoperative Radiotherapy (RT) or RT alone was the standard therapeutic modality for loco regionally advanced HNSCC (LA-HNSCC). Since chemotherapeutic agents were identified to have additional effects when combined with RT, Chemo-Radiotherapy (CRT) has become the standard treatment over the last decade for patients with LA-HNSCC who were not candidates for surgery. Despite the heterogeneity of both tumor location and genetic aberrations, 90% of HNCs are Histologically Squamous Cell Carcinomas (HNSCCs). Hereby we present a case series of patients with HNSCC who were benefited with Anti-EGFR therapy with a prolonged survival.
Cancer, 1988
patients with advanced untreated head and neck squamous cell cancer (HNSCC) received neoadjuvant chemotherapy (NAC) with two or three courses of the CABO combination (methotrexate 40 mg/m2 intravenously (IV) on days 1 and 15; CDDP 50 mg/m2 IV on day 4; bleomycin 10 mg IV on days 1,8, and 15; and vincristine 2 mg IV on days 1,8, and 15 every 3 weeks) prior to surgery and/or radiotherapy. Of the 123 patients evaluable for response to chemotherapy, 19 (15.4%) had a complete remission and 59 (48%) a partial response, yielding a 63.4% overall response rate. Response rate was significantly correlated with the performance status (PS) (P = O.OOl), the stage (P = 0.005), and the T class (P = 0.02X 107 patients completed subsequent local treatment (87 with radiotherapy and 20 with surgery +radiotherapy). The median survival of the 124 patients evaluable for survival was 14.7 months and the overall survival rate at 3 years was 24%. The median survival and the overall survival at 3 years for the surgical subgroup were 24.7 months and 38% and for the radiotherapy subgroup were 14.3 months and 22%. These results were compared with those obtained in a historical control group of 79 patients treated in our institute with short courses of chemotherapy regimens, which did not include cisplatin, followed by radiotherapy (29 patients) or local treatments alone (26 patients with radiotherapy and 24 patients with surgery k radiotherapy) between January 1976 and December 1980. Most of the patient characteristics were evenly distributed (age, sex, and primary sites) except that more advanced lesions were included in the NAC group (Stage IV. 85% versus 62%; T4: 65% versus 42%; N2-3: 48% versus 29%). The overall survival was significantly higher in patients receiving NAC than in the historical control group, comparing both the groups taken as a whole (P < 0.05) and the surgery f radiotherapy (P < 0.05) and the radiotherapy (P < 0.02) subgroups.
Clinical Outcomes of Head and Neck Cancer Patients Who Undergo Resection, But Forgo Adjuvant Therapy
Anticancer Research
Background/Aim: This study aimed to evaluate the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) who underwent resection and refused the recommended adjuvant therapy. Patients and Methods: Locoregional recurrence-free survival (LRRFS) and time to progression (TTP) were assessed in HNSCC patients treated with surgery who declined some or all adjuvant therapy (refusal group (RG)) compared to those who received the recommended adjuvant therapy (TG). Results: With a median follow-up of 23 months, the 2-year LRRFS was significantly lower in the 17 patients from the RG compared to the 152 patients from the TG: 23.1% vs. 69%, HR=0.30, 95% confidence incidence (CI)=0.15-0.59; p<0.001. The mean TTP was 12 months in the RG and was not reached in the TG (p<0.001). Conclusion: Patients with HNSCC who declined the recommended adjuvant therapy had a recurrence rate of 50% within a year. Adjuvant radiation therapy is the standard of care for resected head and neck squamous cell carcinoma (HNSCC) with adverse risk factors, such as the presence of multiple involved nodes, inadequate surgical margins, pT3-4 disease, 4885 This article is freely accessible online.
Oral Oncology, 2014
Objective: Overexpression of epidermal growth factor receptor (EGFR) in many cancers makes it an attractive therapeutic target. This study evaluated the clinical utility of nimotuzumab, a monoclonal anti-EGFR antibody, used concurrently with radiotherapy (RT) and chemoradiotherapy (CRT) in squamous cell carcinoma of the head and neck (SCCHN). Methods: This open-label study randomized 92 treatment-naïve patients (1:1) with advanced SCCHN into chemoradiation (CRT ± nimotuzumab) or radiation (RT ± nimotuzumab) group by investigator's discretion; these were further randomized into CRT + nimotuzumab or CRT and RT + nimotuzumab or RT groups, respectively. Treatment included 6 cycles each of cisplatin (50 mg/week), nimotuzumab (200 mg/week), and RT (total dose, 60-66 Gy). Response (tumor size reduction) was assessed at Month 6 post-treatment and survival, at Month 60. Results: Forty and 36 patients in the chemoradiation and radiation groups, respectively (intent-to-treat population) were evaluated. Overall response at Month 6 post-treatment was 100% with CRT + nimotuzumab, 70% with CRT, 76% with RT + nimotuzumab, and 37% with RT. At Month 60, overall survival was 57% with CRT + nimotuzumab, 26% with CRT (P = 0.03), 39% with RT + nimotuzumab, and 26% with RT (P > 0.05). Median overall survival was not reached for CRT + nimotuzumab; it was 21.94 months for CRT (P = 0.0078), 14.36 months for RT + nimotuzumab, and 12.78 months for RT (P = 0.45). Risk of death was 64% lower with CRT + nimotuzumab than with CRT (95%CI: 0.37, 1.56), and 24% lower with RT + nimotuzumab than with RT (95%CI: 0.16, 0.79). Thus nimotuzumab was safe and well tolerated with few mild to moderate self-limiting adverse events. Conclusion: Concurrent use of nimotuzumab with CRT/RT is safe and provides long-term survival benefit.
JCI Insight, 2017
BACKGROUND. EGFR and Src family kinases are upregulated in head and neck squamous cell carcinoma (HNSCC). EGFR interacts with Src to activate STAT3 signaling, and dual EGFR-Src targeting is synergistic in HNSCC preclinical models. pSrc overexpression predicted resistance to the EGFR inhibitor, erlotinib, in a prior window trial. We conducted a 4-arm window trial to identify biomarkers associated with response to EGFR and/or Src inhibition. METHODS. Patients with operable stage II-IVa HNSCC were randomized to 7-21 days of neoadjuvant erlotinib, the Src inhibitor dasatinib, the combination of both, or placebo. Paired tumor specimens were collected before and after treatment. Pharmacodynamic expression of EGFR and Src pathway components was evaluated by IHC of tissue microarrays and reverse-phase protein array of tissue lysates. Candidate biomarkers were assessed for correlation with change in tumor size. RESULTS. From April 2009 to December 2012, 58 patients were randomized and 55 were treated. There was a significant decrease in tumor size in both erlotinib arms (P = 0.0014); however, no effect was seen with dasatinib alone (P = 0.24). High baseline pMAPK expression was associated with response to erlotinib (P = 0.03). High baseline pSTAT3 was associated with resistance to dasatinib (P = 0.099). CONCLUSIONS. Brief exposure to erlotinib significantly decreased tumor size in operable HNSCC, with no additive effect from dasatinib. Baseline pMAPK expression warrants further study as a response biomarker for anti-EGFR therapy. Basal expression of pSTAT3 may be independent of Src, explain therapeutic resistance, and preclude development of dasatinib in biomarker-unselected cohorts. TRIAL REGISTRATION. NCT00779389.
BMC Cancer
Objectives The optimal duration of anti-PD-1 for cancer therapy has not been tested, especially when using combination therapy. Epidermal growth factor receptor (EGFR) pathway blocker was the top compound that enhanced T-cell killing of tumor cells in a high-throughput immune-oncology screen, possibly by stimulate the antigen presentation machinery and other mechanisms. We explored the effect of combination of EGFR inhibition with a short course of anti-PD-1 therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Method We analyzed the effect of a short course of anti-PD-1 with continuous afatinib on the survival of a real-world cohort of R/M HNSCC patients. Patient characteristics, treatments, efficacies, and toxicities were reviewed and recorded for analysis. Results From November 2016 to May 2018, 51 consecutive patients received pembrolizumab and afatinib. The cutoff date was June 30, 2022. The most common toxicities (all grades) were ...
Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma
International Journal of Molecular Sciences
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosa of the upper aerodigestive tract. Despite multimodality treatments approximately half of all patients with locally advanced disease relapse and the prognosis of patients with recurrent or metastatic HNSCC is dismal. The introduction of checkpoint inhibitors improved the treatment options for these patients and pembrolizumab alone or in combination with a platinum and fluorouracil is now the standard of care for first-line therapy. However, approximately only one third of unselected patients respond to this combination and the response rate to checkpoint inhibitors alone is even lower. This shows that there is an urgent need to improve prognostication and prediction of treatment benefits in patients with HNSCC. In this review, we summarize the most relevant risk factors in the field and discuss their roles and limitations. The human papilloma virus (HPV) status for patients with oropharyn...