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Published on: April 22, 2019
Duvelisib with Docetaxel for Patients with Anti-PD-1 Refractory, Recurrent, or Metastatic Head and Neck Squamous Cell
Glenn J Hanna1, L B Oakley1, R Shi2
1Center for Head and Neck Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Purpose:
Treatments after anti-PD-1 therapy for patients with recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) are limited. Blocking PI3K signaling may lead to tumor immunomodulation and enhanced taxane sensitivity. This phase 2 trial evaluated dual, selective PI3Kδ/γ inhibition with docetaxel in patients with anti-PD-1 refractory recurrent, metastatic HNSCC.
Patients And Methods:
Patients received duvelisib (25 mg orally twice daily) with docetaxel (75 mg/m2 IV) every 21 days. The primary endpoint was overall response rate (RECIST v1.1), using a Simon two-stage design. Secondary endpoints were safety, progression-free survival, and overall survival, and exploratory endpoints were correlating immunologic and genomic parameters with outcomes.
Results:
From 11/1/21 to 10/10/23, 26 patients were enrolled (median age: 64, 96% men, 54% with human papillomavirus+ disease; primary site: 12 oropharynx, 11 oral cavity, and 3 larynx/hypopharynx. The best overall response rate was 19% [5/26; 95% confidence interval (CI), 6.8%-40.7%]. All were partial responses [median duration: 5.1 months (0.7-15.5)]; 46% (12/26) exhibited stable disease, and 32% (8/26) exhibited progression (1 unevaluable). Two patients remain on-treatment at data cutoff; 25% (6/24) came off for toxicity. Grade 3+ treatment-related adverse events were observed in 50% (13/26), most often elevated liver function tests (6, 23%). No deaths were treatment-related. At median follow-up of 6.5 months (0.7-26), median progression-free survival was 2.8 months (95% CI, 1.9-7.0); 17/26 patients had died. Median overall survival was 10.2 months (95% CI, 6.7-15.9), favoring human papillomavirus-negative patients. Greater tumor CD3+/CD8+ T-cell infiltration trended with improved outcomes.
Conclusions:
We report a favorable response rate when combining a selective PI3K pathway inhibitor and taxane in patients with anti-PD-1 refractory HNSCC.
Insights
This study combined a PI3K inhibitor with docetaxel for recurrent head and neck cancer after anti-PD-1 therapy. The combination showed a 19% response rate, offering a new treatment option for refractory HNSCC patients.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) after anti-PD-1 therapy has limited treatment options.
- PI3K signaling inhibition may modulate the tumor microenvironment and increase sensitivity to taxanes.
Purpose of the Study:
- To evaluate the efficacy and safety of dual PI3Kδ/γ inhibition with docetaxel in patients with anti-PD-1 refractory HNSCC.
- To assess the overall response rate (ORR) as the primary endpoint.
Main Methods:
- A phase 2 trial administered duvelisib (PI3Kδ/γ inhibitor) plus docetaxel every 21 days.
- The study used a Simon two-stage design to evaluate ORR (RECIST v1.1).
- Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS).
Main Results:
- The overall response rate was 19% (5/26 patients), with all partial responses. Median duration of response was 5.1 months.
- 46% of patients had stable disease; 32% had disease progression. Median PFS was 2.8 months, and median OS was 10.2 months.
- Grade 3+ treatment-related adverse events occurred in 50% of patients, primarily elevated liver function tests. HPV-negative patients showed improved OS.
Conclusions:
- Combining a selective PI3K inhibitor with docetaxel demonstrates a favorable response rate in anti-PD-1 refractory HNSCC.
- This combination therapy represents a potential new treatment strategy for patients with limited options.
- Further research into immunologic and genomic correlates may optimize treatment selection and outcomes.
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