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|Ref Type||Journal Article|
|Authors||Dunn LA, Fury MG, Xiao H, Baxi SS, Sherman EJ, Korte S, Pfister C, Haque S, Katabi N, Ho AL, Pfister DG|
|Title||A phase II study of temsirolimus added to low-dose weekly carboplatin and paclitaxel for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).|
|Journal||Annals of oncology : official journal of the European Society for Medical Oncology|
|Date||2017 Oct 01|
|Abstract Text||Activating events along the PI3K/mTOR pathway are common in head and neck squamous cell carcinomas (HNSCC), and preclinical studies suggest additive or synergistic effects when combining mTORC1 inhibitors with carboplatin and paclitaxel chemotherapy.In this single-institution phase II study, the combination of temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m2 administered on days 1 and 8 of a 21-day cycle was evaluated in 36 patients with recurrent and/or metastatic (R/M) HNSCC. The primary end point was objective response rate after two cycles of treatment. Secondary end points include the safety and tolerability profile and overall survival. Correlative studies with exome mutational analysis were performed in pre-treatment biopsy samples from 21 patients.Fifteen (41.7%) patients had an objective response, which were all partial responses, and 19 (52.3%) patients had stable disease as best response. The two patients who were designated as 'non-responders' were removed from study prior to two cycles of treatment, but are included in the efficacy and safety analyses. The median duration on study was 5.3 months and the median progression-free survival and overall survival were 5.9 months (95% confidence interval, 4.8-7.1) and 12.8 months (95% confidence interval, 9.8-15.8), respectively. The most common grade 3 and 4 adverse events were hematologic toxicities. Three (3.8%) patients developed neutropenic fever on study. Three of four patients with PIK3CA mutations experienced tumor regressions, and responses were also seen in patients with other genetic alterations in the PI3K/mTOR pathway.The combination of temsirolimus with low-dose weekly carboplatin and paclitaxel appears to have meaningful clinical efficacy in the treatment of R/M HNSCC. This regimen has a relatively high response rate compared to other treatments evaluated in R/M HNSCC, and potential associations with genetic alterations in the PI3K/mTOR pathway should be further explored.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|PIK3CA mutant||head and neck squamous cell carcinoma||predicted - sensitive||Carboplatin + Paclitaxel + Temsirolimus||Phase II||Actionable||In a Phase II trial, two patients with head and neck squamous cell carcinoma harboring a PIK3CA mutation who had stable disease demonstrated some tumor regression when treated with the combination of Torisel (temsirolimus), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28961834).||28961834|
|PIK3CA E545K||head and neck squamous cell carcinoma||predicted - sensitive||Carboplatin + Paclitaxel + Temsirolimus||Case Reports/Case Series||Actionable||In a Phase II trial, a patient with head and neck squamous cell carcinoma harboring PIK3CA E545K demonstrated a partial response when treated with the combination of Torisel (temsirolimus), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28961834).||28961834|
|Unknown unknown||head and neck squamous cell carcinoma||not applicable||Carboplatin + Paclitaxel + Temsirolimus||Phase II||Actionable||In a Phase II trial, the combination of Torisel (temsirolimus), Paraplatin (carboplatin), and Taxol (paclitaxel) resulted in an objective response rate of 41.7% (15/36), which included all partial responses, and 52.3% (19/36) had stable disease (PMID: 28961834).||28961834|