Hypomagnesemia as a predictor of the efficacy of combination EGFR-targeted drugs versus EGFR ADCs alone in HNSCC.

146 Background: EGFR-targeted drugs and ADCs in combination with EGFR-conjugated chemotherapy drugs can both cause hypomagnesemia. However, the predictive value of hypomagnesemia in response to treatment for head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: This study retrospectively analyzed patients who participated in clinical trials of EGFR-targeted drugs and EGFR ADCs for HNSCC and solid tumors, from February 24, 2022, to March 25, 2024. The primary endpoint of the study was time to treatment failure (TTF). Results: This study conducted a retrospective analysis of 68 patients . All patients exhibited normal baseline serum magnesium levels prior to treatment, but following two cycles of treatment, varying degrees of hypomagnesemia were observed among them. Among the 46 patients who received 2 cycles of combination therapy with EGFR-targeted drugs, 33 were hypomagnesemia and 13 were normal serum magnesium, ORR[90.9%vs. 8.5%,(P=0.002)] (Table), TTF [151 days (95% CI: 212-380) vs. 87 days (95% CI: 52-230), HR 0.576 (95% CI: 0.270–1.230,P = 0.021)]. Among the 22 patients who received EGFR ADC alone for 2 cycles, 8 were hypomagnesemia and 14 were normal serum magnesium, ORR [37.5% vs.28.6%, (P=0.549)] (Table), TTF [97.5 days (95% CI: 68-300) vs. 108.5 days (95% CI: 60-160), HR of 0.877 (95% CI: 0.339–2.263; P = 0.547)]. Conclusions: The study demonstrates that, the occurrence of hypomagnesemia is associated with ORR and TTF following two cycles of combination of EFGR-targeted drugs, not observed in patients receiving EGFR ADCs as monotherapy in HNSCC. [Table: see text]