From Local Control to Metastatic Disease: Real-World Case Discussion in Advanced SCAC Management

Advanced Disease Case Study and Treatment Selection

This case involves a man aged 63 years with T2N0 disease who achieved complete clinical response to standard chemoradiation but developed metastatic disease 18 months later, presenting with liver lesions and pulmonary nodules. Biopsy confirmed metastatic squamous cell carcinoma with PD-L1 combined positive score of greater than 1%, demonstrating the unfortunate reality of disease progression despite initial treatment success. The patient maintained good performance status, making him a candidate for aggressive systemic therapy.

Treatment selection factors for combination therapy vs chemotherapy alone include patient fitness, contraindications to immunotherapy, and biomarker status. Although PD-L1 testing was performed, subgroup analysis from PODIUM-303 showed benefit regardless of PD-L1 status, making it less critical for treatment decisions. Important contraindications include solid organ transplant recipients, where checkpoint inhibitors risk organ rejection and should be avoided.

The PODIUM-303 study data support carboplatin/paclitaxel plus retifanlimab as emerging standard of care, with compelling improvements in progression-free survival and response rates. The study allowed 45% crossover, which may limit overall survival interpretation, but the primary end point of PFS was met with statistical significance. Ongoing E2176 study with different design elements (2:1 randomization, no crossover, nivolumab instead of retifanlimab, 2 years vs 1 year of immunotherapy) may provide additional comparative data.