(106) Comparing Everolimus to Cetuximab as Adjuvant Therapy: TP53 Mutant HNSCC

Introduction: Patients with TP53 mutant head and neck squamous cell carcinoma (p53mHNSCC) have poor response to treatment due to resistance to chemoradiotherapy. Platinum therapies have a high toxicity profile and the alternative, cetuximab, has a high resistance profile. Everolimus (an mTOR inhibitor) has had promising results in Phase II trials. Therefore, we compare the efficacy of cetuximab to everolimus in inhibiting growth of p53mHNSCC in a minimal residual disease (MRD) tumor xenograft model.

Methods: In this in vivo randomized controlled trial conducted from Aug 2021 to Oct 2021, athymic nude mice were implanted with p53mHNSCC FaDu cells and randomized into vehicle, cetuximab, or everolimus treatment groups. The vehicle group received saline (n=5), the cetuximab group (n=5) received biweekly cetuximab intraperitoneally (0.25 mg) and the everolimus group (n=5) received 5 mg/kg/b.w. daily via oral gavage. Treatment was started three days after tumor implantation to mimic MRD models. The tumor volumes were measured twice weekly for 90 days or until humane endpoints were met. Tumor growth charts were made and statistical analyses run.

Results: Our results demonstrated equal tumor inhibition by everolimus and Cetuximab on the growth of FaDu tumor cell xenografts for 40 days while all vehicle group mice were sacrificed in this time period due to meeting endpoint criteria. However, by day 50 the average tumor volume for the everolimus treatment group was 167 mm3 (CI95% 156-177) while the average volume of the cetuximab treatment group was 388 mm3 (CI95% 370-405) during the same time (p=0.00004). FaDu xenografts treated with Cetuximab developed resistant tumors while the xenografts treated with everolimus failed to elicit any resistance to treatment and exhibited sustained sensitivity for 13 weeks. Taken together, this study establishes a lack of treatment resistance to medium term everolimus treatment in p53mHNSCC when compared to cetuximab.

Conclusions: Everolimus holds promise as an effective adjuvant therapy for p53mHNSCC and tumor resistance did not develop when compared to cetuximab.