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mTOR inhibitor use in head and neck squamous cell carcinoma: A meta-analysis on survival, tumor response, and
Jaimin Patel1, Shaun A Nguyen1, Besim Ogretmen1
1Head and Neck Tumor Center, Hollings Cancer Center, Department of Otolaryngology-Head and Neck Surgery Medical University of South Carolina Charleston South Carolina USA.
Background:
Head and neck squamous cell carcinoma (HNSCC) has been rising in incidence primarily related to HPV-associated oropharyngeal cancers. Novel molecular therapeutics are evolving with the mTOR pathway as a new target. Previous studies have shown variable outcomes with relatively low toxicity. This study reports the tumor response, survivability, and toxicity of mTOR inhibitors (mTORi) in HNSCC. Despite expanding research on this pathway, there remains controversy around mTORi use for treatment of HNSCC.
Materials And Methods:
Studies were included if: (a) Used mTORi alone or in combination with other treatment modalities in HNSCC. (b) Site of cancer included were one of the following: nasopharyngeal, oral cavity, oropharynx, hypopharynx or larynx. (c) All stages of cancer and treatment stage (neoadjuvant, adjuvant, and palliative) were included. The rate of adverse events (AEs), tumor response, progression free survival, and overall survival were meta-analyzed.
Results:
From 1299 publications only 11 studies met inclusion criteria with a combined 232 total patients treated. Two studies used mTORi neoadjuvantly, five adjuvantly, and four in palliative/unresectable/metastatic setting. Monotherapeutic mTORi resulted in stabilization of disease (52.5%), but partial response was the most common response when mTORi were combined with chemotherapy and/or radiation (CRT) (48.1%). Survival rate was the highest in the mTORi combined with CRT. Hyperglycemia of any grade was the most commonly reported toxicity while grade 3 or less AEs were the most common grade of toxicity.
Conclusion:
The use of mTORi as monotherapy in HNSCC has thus far not yielded significant tumor response, however, in combination with other agents, an improved partial tumor response is evident that may or may not be associated with the addition of mTORi. Although adverse events were common, grade 4/5 AEs were uncommon. Further prospective, randomized clinical trials are necessary to confirm the direct roles of these agents in HNSCC tumor response.
Level Of Evidence:
2a.
Insights
mTOR inhibitors (mTORi) show limited tumor response as monotherapy for head and neck squamous cell carcinoma (HNSCC). Combination therapy with mTORi and chemotherapy/radiation (CRT) demonstrates improved partial tumor response and survival rates, with manageable toxicity.
Area of Science:
- Oncology
- Molecular Therapeutics
- Cancer Research
Background:
- Head and neck squamous cell carcinoma (HNSCC) incidence is rising, particularly HPV-associated oropharyngeal cancers.
- The mTOR pathway is an emerging target for novel molecular therapeutics in HNSCC.
- Previous studies on mTOR inhibitors (mTORi) in HNSCC have shown variable outcomes and relatively low toxicity.
Purpose of the Study:
- To meta-analyze the tumor response, survivability, and toxicity of mTOR inhibitors (mTORi) in HNSCC.
- To evaluate the efficacy of mTORi as monotherapy versus combination therapy in HNSCC treatment.
- To assess the safety profile and adverse events associated with mTORi use in HNSCC.
Main Methods:
- A meta-analysis was conducted on 11 studies, including 232 patients with HNSCC.
- Studies utilized mTORi alone or in combination with chemotherapy and/or radiation (CRT).
- Outcomes analyzed included adverse events (AEs), tumor response, progression-free survival, and overall survival.
Main Results:
- Monotherapeutic mTORi resulted in disease stabilization in 52.5% of patients.
- Combination therapy with mTORi and CRT showed partial response in 48.1% of patients, with the highest survival rates.
- Hyperglycemia was the most common toxicity; grade 3 or less AEs were most frequent.
Conclusions:
- mTORi monotherapy has not shown significant tumor response in HNSCC.
- Combination therapy with mTORi and other agents demonstrates improved partial tumor response.
- While AEs are common, severe (grade 4/5) AEs are infrequent, warranting further prospective trials.
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