PFS Remains Unaffected in Patients With Advanced Biliary Tract Cancer After Adding Ramucirumab or Merestinib to Chemo

Progression-free survival remained unaffected in patients with advanced biliary tract cancer after clinicians added either ramucirumab or merestinib to first-line chemotherapy.

The role of the targeted inhibitors ramucirumab [Cyramza] or merestinib (LY2801653) first-line cisplatin–gemcitabine in patients with locally advanced or metastatic biliary tract cancer remains investigational, according to new data from The Lancet.1

In a randomized, double-blind, phase-2 study researchers looked at 309 patients assigned to either 8 mg/kg of intravenous ramucirumab (n=106), 80 mg of oral merestinib (n=102), or pooled placebo (n=101), along with cisplatin at 25 mg/m2 and gemcitabine at 1000 mg/m2 on days 1 and 8 in 21-day cycles, for a maximum of 8 cycles.

At the data cut off 10.9 months the median progression free survival (PFS) of patients on ramucirumab was 6.5 months (80% CI 5.7–7.1), 7 months (80% CI, 6.22–7.1) in the merestinib group, and 6.6 months (80% CI, 5.6–6.8) in the pooled placebo group. When comparing patients in the ramucirumab group versus those in the placebo group the hazard ratio was 1.12 (80% CI, .90–1.4; P = .48) and was .92 in the merestinib versus placebo arm (80% CI, .73–1.15; P = .64). According to the researchers these data showed that each inhibitor was tolerated well in the patient groups but did not improve PFS in them.

Enrolled patients had histologically or cytologically confirmed, non-resectable, recurrent, or metastatic biliary tract adenocarcinoma. They were untreated and 18 years old or older, with an ECOG performance status of 0 or 1, and had an estimated life expectancy of 3 months or more.

Biliary tract cancers are rare and aggressive gastrointestinal malignancies where approximately half of patients survive for less than 1 year after a diagnosis with advanced disease. Thus, researchers were hoping that results from this phase 2 study would allow them to treatment patients longer, but the results show that the chemotherapy and targeted therapy combination remain in the investigational phase.

However, these treatments were both well tolerated by patients when looking at adverse event [AE] data from both arms. The most common grade 3 or worse adverse events were neutropenia with 51 (49%) patients in the ramucirumab group experiencing it compared to 48 (47%) patients in the merestinib group, and 33 patients in the pooled placebo group. This was followed by thrombocytopenia, 36 [35%] patients, 19 patients, and 17 patients, respectively, and anemia.

Serious AEs occurred in 53 (51%) patients in the ramucirumab group, 56 patients (55%) in the merestinib group, and 48 (48%) in the pooled placebo group. Treatment related deaths occurred in 1 patient from the ramucirumab group who had a heart attack, and 2 patients in the merestinib group with 1 patient dying due to pulmonary embolism and 1 due to sepsis.

“The role of these targeted inhibitors remains investigational, highlighting the need for further understanding of biliary tract malignancies and the contribution of molecular selection,” the researchers concluded.

Reference

Valle JW, Vogel A, Denlinger CS, He AR, et al. Addition of ramucirumab or merestinib to standard first-line chemotherapy for locally advanced or metastatic biliary tract cancer: a randomised, double-blind, multicentre, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1468-1482. doi: 10.1016/S1470-2045(21)00409-5