Reference Detail

Ref Type

Journal Article

PMID

(28961834)

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	Vol	Issue	Date	Pages	Journal Short Title
Annals of oncology : official journal of the European Society for Medical Oncology	28	10	2017 Oct 01	2533-2538	Ann Oncol

URL

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.

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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 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
PTEN R130Q	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 PTEN R130Q demonstrated a partial response when treated with the combination of Torisel (temsirolimus), Paraplatin (carboplatin), and Taxol (paclitaxel) (PMID: 28961834).	28961834
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