Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study

Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti–programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. Results Among 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade ≥ 3 event. Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. Conclusion Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.

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Phase II study of gemcitabine concurrent with radiation in locally advanced squamous cell carcinoma of head and neck: Trial of the Cancer Research Group Pakistan

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.15520 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 15520-15520 ◽

Cited By ~ 1

Author(s):

A. A. Javed ◽

A. Shaharyar ◽

I. H. Shah ◽

M. A. Shah ◽

T. N. Ansari ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Total Dose ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Overall Response Rate ◽

Response Rate ◽

Locally Advanced ◽

Overall Response ◽

Grade 3

15520 Background: The optimum radiosensitizing dose and schedule of gemcitabine for squamous cell carcinoma of head and neck are not known. The objectives of this study were to evaluate the efficacy and toxicity of weekly gemcitabine as a radiosensitizer concurrent with radical radiotherapy in locally advanced head and neck cancer. Method: Thirty-nine patients with stage III or IV B inoperable carcinoma of head and neck were enrolled. Eligible patients had histopathologically confirmed squamous cell carcinoma with age between 18–70 years. Patients had a KPS >70 with an adequate marrow, hepatic and renal function. No prior chemotherapy or radiotherapy was allowed. Patients with nasopharyngeal, glottic or sub-glottic cancer were excluded. Gemcitabine 150 mg/m2 or a total dose not exceeding 200 mg was given on day 1,8,15,22,29, and 36 during radiation treatment. Gemcitabine was infused in 200 ml of normal saline in 2 hours and radiation was delivered two hours after the completion of gemcitabine infusion. Conventional fractionation was used to deliver a total dose of 66 Gy. CTC version 2.0 of NCI and RTOG/EORTC Late Radiation Morbidity Scoring Scheme were used for evaluation of toxicity and RECIST was used for response evaluation. Results: Only 35 patients were considered evaluable for response. Complete response was seen in 8 (22.9%) (95% CI; 10.4–40.1%), partial response in 25 (71.4%), with an overall response rate of 94.3% (95% CI; 80.8–99.3%). All the thirty-nine patients were evaluable for toxicity. Grade 3 and 4 mucositis was seen in 28 (71.8%) and 2 (5.1%) patients respectively. Grade 3 pharyngeal toxicity was seen in 6 (15.4%). One patient developed pharyngo-cutaneous fistula. Despite vigorous symptomatic and supportive care acute toxicities led to treatment interruption in 16 (41%) of patients. Conclusion: Weekly gemcitabine at a dose of 150mg/m2 concurrent with radiation therapy gives a high overall response rate and a high rate of acute toxicity. No significant financial relationships to disclose.

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Phase II study of biweekly dose-intense docetaxel plus gemcitabine (GEM/DOC) in patients with recurrent locoregional or metastatic head and neck squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.5534 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 5534-5534 ◽

Cited By ~ 1

Author(s):

Ammar Sukari ◽

Zyad Kafri ◽

Lance K. Heilbrun ◽

George H. Yoo ◽

Heather a Mulrenan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Disease Progression ◽

Annual Meeting ◽

Phase Ii ◽

Squamous Cell ◽

Response Rate ◽

Phase Ii Study ◽

Neck Squamous Cell Carcinoma

5534 Notice of Retraction: "Phase II study of biweekly dose-intense docetaxel plus gemcitabine (GEM/DOC) in patients with recurrent locoregional or metastatic head and neck squamous cell carcinoma." ASCO's Confidentiality Policy requires that abstracts be considered confidential and embargoed from the time of submission until the findings have been publicly released in conjunction with the ASCO Annual Meeting. Abstract 5534, published in the 2012 Annual Meeting Proceedings Part I, a supplement to the Journal of Clinical Oncology, violated this policy and has been retracted from publication and presentation at the 2012 ASCO Annual Meeting. Background: Patients with metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, limited treatment options, and median survival of 6 to 9 months. Docetaxel and gemcitabine have both shown activity in HNSCC. The optimal combination, dosing, and scheduling of both drugs is, however, unknown. Thus, we investigated the efficacy and safety of biweekly dose intense GEM/DOC in patients with recurrent locoregional or metastatic HNSCC. Methods: An open-label, single-institution, single-arm, phase II study was conducted for patients who were previously treated with no more than two cytotoxic regimens. The patients received docetaxel (60 mg/m2IV) and gemcitabine (3000 mg/m2 IV) on day 1. The treatments were repeated every 14 days (one cycle), until disease progression or unacceptable toxicity. The primary end point was response rate. RECIST-defined response was evaluated every 4 cycles and toxicities were evaluated at each cycle. Results: A total of 36 patients were enrolled (M:F 26:10; median age (range), 60 years (46-79); performance status 0-1) , 29 of whom were response-evaluable. The patients received a median of 4 cycles (range 0-24). Of these 29 patients, none achieved complete response (CR) and 6 demonstrated a partial response (PR). Thus, the overall response rate was 21% (95% confidence interval [CI], 0.10 – 0.38). Ten patients had stable disease (SD), resulting in tumor control (CR or PR or SD) in 16 of 29 patients (55%), whereas 13 patients (45%) had disease progression. The median response duration was 3.2 months (80% CI: 2.0 – 6.1 months). For all 36 patients, the median overall survival was 4.2 months (95% CI: 2.4 – 7.0 months). Myelosuppression was the most common adverse event. Grade 3-4 neutropenia and anemia were observed in 10 (30%) and 13 (39%) patients, respectively. None of these patients, however, had febrile neutropenia or bleeding events, and there were no treatment-related deaths. Conclusions: The combination of biweekly dose intense GEM/DOC was tolerable and active regimen in patients with recurrent locoregional or metastatic HNSCC. Our findings warrant further investigation in a larger patient population.

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