What needs to be understood is the big reduction in adverse effects with CAVATAK, vs checkpoint inhibitor already approved for melanoma: Yervoy. Cavatak has NO GRADE III adverse effects, and frankly minimal grade II, just look at the poster at the Viralytics website.
Now best to compare phase II data to be consistent, Yervoy phase II data, in the trial I enclose below, they are trying to reduce the severe immune related GI toxicity caused by Yervoy, by using a steroid that blunts the immune response. All patients receive Yervoy, half get the steroid half get placebo , ALL get Yervoy.
Median survival 17.7 months with steroid, 19.3 months with no steroid.
Cavatak median survival of 26 months is therefore quite exciting, especially when you realize Yervoy is an APPROVED melanoma treatment now AND look at patient characteristics, and see that 61% of the CAVATAK patients were stage IV!
NO GRADE III or IV Adverse events in CAVATAK trial is phenomenal for a cancer drug.
Even Grade II events are quite rare!!!!!
Great results, congrats to Darren Shafren the Virologist in Newcastle that made this discovery, expect the combo trial with checkpoint inhibitor to be even better if preclinical data is any indication.
Abstract
Purpose: Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated with ipilimumab. A randomized, double-blind, placebo-controlled, multicenter, multinational phase II trial was conducted to determine whether prophylactic budesonide (Entocort EC), a nonabsorbed oral steroid, reduced the rate of grade ≥2 diarrhea in ipilimumab-treated patients with advanced melanoma.
Experimental Design: Previously treated and treatment-naïve patients (N = 115) with unresectable stage III or IV melanoma received open-label ipilimumab (10 mg/kg every 3 weeks for four doses) with daily blinded budesonide (group A) or placebo (group B) through week 16. The first scheduled tumor evaluation was at week 12; eligible patients received maintenance treatment starting at week 24. Diarrhea was assessed using Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Patients kept a diary describing their bowel habits.
Results: Budesonide did not affect the rate of grade ≥2 diarrhea, which occurred in 32.7% and 35.0% of patients in groups A and B, respectively. There were no bowel perforations or treatment-related deaths. Best overall response rates were 12.1% in group A and 15.8% in group B, with a median overall survival of 17.7 and 19.3 months, respectively. Within each group, the disease control rate was higher in patients with grade 3 to 4 irAEs than in patients with grade 0 to 2 irAEs, although many patients with grade 1 to 2 irAEs experienced clinical benefit. Novel patterns of response to ipilimumab were observed.
Conclusions: Ipilimumab shows activity in advanced melanoma, with encouraging survival and manageable adverse events. Budesonide should not be used prophylactically for grade ≥2 diarrhea associated with ipilimumab therapy. (Clin Cancer Res 2009;15(17):5591–8)
VLA Price at posting:
66.5¢ Sentiment: None Disclosure: Held
