Dr Msaouel on a Study of Panitumumab-Based EGFR Blockade in SMARCB1-Deficient RMC

“In our preclinical models, we tested the efficacy of the monoclonal antibody panitumumab against wild-type EGFR vs erlotinib vs vehicle control.We found, both in our patient-derived xenograft models and our cell line–derived xenograft models, that the efficacy of panitumumab was much higher than that of erlotinib.”

Pavlos Msaouel, MD, PhD, an associate professor in the Department of Genitourinary Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discussed the background of a study evaluating the prospective clinical activity of panitumumab (Vectibix)-based EGFR blockade in SMARCB1-deficient renal medullary carcinoma (RMC).

Preclinical research evaluating EGFR-targeted therapies in RMC demonstrated promising activity for the monoclonal antibody panitumumab, particularly when compared with the EGFR TKI erlotinib (Tarceva), Msaouel began. Msaouel and his coinvestigators assessed the efficacy of panitumumab in both patient-derived xenograft models and cell line–derived xenograft models, comparing outcomes with those achieved using erlotinib and vehicle control, he added. Across these models, panitumumab consistently produced superior antitumor activity, suggesting that antibody-based inhibition of wild-type EGFR may represent a more effective therapeutic strategy in RMC than tyrosine kinase inhibition, he said.

Earlier studies evaluating the combination of erlotinib and bevacizumab (Avastin) demonstrated evidence of clinical activity, with objective responses observed in approximately 20% of heavily pretreated patients with RMC, Msaouel said. Those data were sufficiently compelling to be incorporated into treatment guidelines, highlighting the potential role of EGFR inhibition in a disease with otherwise limited therapeutic options, he noted.

The strong preclinical results with panitumumab prompted investigators to rapidly translate these findings into a clinical setting, Msaouel said. Rather than developing an entirely new treatment approach, researchers leveraged an existing regimen that had originally been designed for inflammatory breast cancer, another rare malignancy characterized by the expression of wild-type EGFR, he added.