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TreeTopp tested whether the HER-family blocker varlitinib added to capecitabine helps bile duct and gallbladder cancer after first-line chemotherapy. It did not: response, progression and survival were the same, and the planned phase 3 part was abandoned. A small gallbladder subgroup hinted at slower progression but the finding was not conclusive.
TreeTopp (NCT03093870) was a global, double-blind, randomised, placebo-controlled phase 2 (part 1 of a planned phase 2/3) in patients with unresectable or metastatic biliary tract cancer, including gallbladder and ampullary cancer, after one prior gemcitabine-containing line. Patients received varlitinib 300 mg or placebo twice daily with capecitabine 1,000 mg/m² twice daily on days 1 to 14 of 21-day cycles. Of 127 treated patients (64 varlitinib, 63 placebo), objective response by independent central review was 9.4 versus 4.8 percent (odds ratio 2.28, p 0.42), median progression-free survival 2.83 versus 2.79 months (hazard ratio 0.90, 95 percent confidence interval 0.60 to 1.37) and overall survival 7.8 versus 7.5 months (hazard ratio 1.11, 0.69 to 1.79). Grade 3 or worse treatment-emergent adverse events occurred in 65.6 versus 58.7 percent. In subgroup analysis varlitinib appeared to prolong progression-free survival in women (4.1 versus 2.8 months, hazard ratio 0.59) and in gallbladder cancer (2.9 versus 1.6 months, hazard ratio 0.55, 0.26 to 1.19). The trial ended varlitinib development in biliary cancer and is the clearest failure of unselected pan-HER inhibition in the disease, in contrast to HER2-selected antibody therapy.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
151 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Objective response rate (independent central review)primary | Varlitinib + capecitabine | 64 | 9.4% | - | 0.42 | link |
| Placebo + capecitabine | 63 | 4.8% | ||||
| Progression-free survivalprimary | Varlitinib + capecitabine | 64 | 2.83 months | 0.9 (0.6 to 1.37) | 0.63 | link |
| Placebo + capecitabine | 63 | 2.79 months | ||||
| Overall survival | Varlitinib + capecitabine | 64 | 7.8 months | 1.11 (0.69 to 1.79) | 0.66 | link |
| Placebo + capecitabine | 63 | 7.5 months | ||||
| Progression-free survival, gallbladder cancer subgroup | Varlitinib + capecitabine | - | 2.9 months | 0.55 (0.26 to 1.19) | - | link |
| Placebo + capecitabine | - | 1.6 months |
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer and the tag failure.
Shares Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer, Cytotoxic chemotherapy and the tag failure.
Shares Small-molecule kinase inhibitors and the tag failure.
Shares Small-molecule kinase inhibitors and the tag failure.
Shares Small-molecule kinase inhibitors and the tag failure.
Shares HER2 and the tag failure.
Shares HER2 and the tag failure.
Shares Small-molecule kinase inhibitors and the tag failure.