Panitumumab in combination with preoperative radiotherapy in patients with locally advanced RAS wildtyp rectal cancer. Results of the multicenter explorative single-arm phase II study NEORIT
Mené sur 54 patients atteints d'un cancer rectal sans mutation du gène RAS et de stade localement avancé (âge médian : 58 ans), cet essai multicentrique de phase II évalue l'efficacité, du point de vue de la réponse pathologique complète, et la toxicité du panitumumab en combinaison avec une radiothérapie pré-opératoire
Background : Studies investigating combinations of anti-epidermal growth factor receptor monoclonal antibodies such as panitumumab or cetuximab with standard chemoradiotherapy protocols in rectal cancer yielded disappointing results. Because of the supposed negative interaction of EGFR-inhibition and chemoradiotherapy we conducted a phase II-study using single agent panitumumab in combination with RT in patients with RAS wildtype with locally advanced rectal cancer. Patients and methods : Patients with RAS wildtyp, locally advanced (clinical stage II or III) rectal cancer localised 0 -12 cm ab ano were eligible for study participation. Primary objective of the study was pathological complete response (pCR). Secondary objectives comprised safety, surgical morbidity, clinical response, tumor downstaging and tumor regression grading according to Dworak. Results : A total of 54 patients with a median age of 58 years were treated. pCR was achieved in 3.7% of patients. A downstaging of primary tumor or lymph nodes was seen in 65% of patients. No hematological toxicity ≥ grade II was seen. The most common non-hematological ≥ grade III toxicities were skin toxicity (24%) and diarrhoea (10 %). Conclusion : Panitumumab in combination with RT as neoadjuvant treatment for LARC showed a favourable toxicity profile but failed to meet the predefined pCR rate to justify further clinical trials.