Response to neoadjuvant targeted therapy in operable head and neck cancer confers survival benefit.
Marco Antonio MascarellaTolani F OlonisakinPurva H RumdeVarun VendraMelonie A NanceSeungwon KimMark W KubikShaum S SridharanMatthew J FerrisMoon J FentonDaniel R ClayburghJames P OhrSonali C JoyceMalabika SenJames G HermanJennifer R GrandisDan P ZandbergUmamaheswar DuvvuriPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2023)
Purpose Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC). Methods A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009-2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n=83) or anti-ErbB3 antibody therapy (n=9) within 28 days of surgery. Clinical to pathologic stage migration was compared to disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed. Results 92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared to control cohort (P=0.048). Patients with pathologic downstage migration had the highest OS (89.5%, 95% CI 75.7-100) compared to those with no stage change (58%, 95% CI 46.2-69.8) or upstage (40%, 95% CI 9.6-70.4, P=0.003). Downstage migration remained a positive prognostic factor for OS (hazard ratio 0.22, 95% CI 0.05-0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers, SOX17 and TAC1 (P=0.0078). Conclusions Brief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylated SOX17 and TAC1.
Keyphrases
- locally advanced
- rectal cancer
- prognostic factors
- lymph node
- end stage renal disease
- patients undergoing
- neoadjuvant chemotherapy
- free survival
- newly diagnosed
- ejection fraction
- chronic kidney disease
- circulating tumor
- minimally invasive
- squamous cell carcinoma
- stem cells
- radiation therapy
- acute coronary syndrome
- mass spectrometry
- cell free
- mesenchymal stem cells
- epidermal growth factor receptor
- high resolution
- phase iii
- single molecule