Randomized phase II trial of combination chemotherapy with panitumumab or bevacizumab for patients with inoperable biliary tract cancer without KRAS exon 2 mutations
Mené sur 88 patients atteints d'un cancer inopérable des voies biliaires ne présentant pas de mutations KRAS, cet essai de phase II compare l'efficacité, du point de vue de la survie sans progression à 6 mois, de l'ajout du panitumumab et de l'ajout du bévacizumab à une chimiothérapie
Biliary tract cancers (BTC) are rare and often diagnosed in late stages with advanced, non‐resectable disease. The targeted agents panitumumab and bevacizumab have shown promising outcomes in combination with chemotherapy in other gastrointestinal (GI ) cancers. We wanted to investigate if panitumumab or bevacizumab was the most promising drug to add to chemotherapy. Eighty‐eight patients were randomized to combination chemotherapy supplemented by either panitumumab 6 mg/kg or bevacizumab 10 mg/kg on day 1 in arm A and B, respectively. All patients received gemcitabine 1000 mg/m2 on day 1, oxaliplatin 60 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice daily on days 1‐7. Treatment was repeated every two weeks until progression or for a maximum of six months. At progression cross‐over was made to the other treatment arm. The primary endpoint was progression free survival (PFS) at six months. With 19 of 45 in arm A and 23 of 43 in arm B PFS at six months, the primary endpoint was not met. The overall response rate (ORR ) was 45% vs 20% (p=0.03), median PFS was 6.1 months vs 8.2 months (p=0.13) and median overall survival (OS) was 9.5 months vs 12.3 months (p=0.47) in arm A and B, respectively. This study showed no consistent differences between adding panitumumab or bevacizumab to chemotherapy in non‐resectable BTC and none of the two regimens qualify for testing in phase III. However, we found a higher response rate in the panitumumab arm with potential implication for future trials in the neoadjuvant setting.