KEYNOTE-158
The basket trial that showed pembrolizumab alone rarely works in bile duct and gallbladder cancer: only 6 of 104 patients responded, though those who did stayed in response for years. It is also the trial behind the tumour-agnostic approvals of pembrolizumab for mismatch-repair-deficient and high mutation-burden cancers, which do apply to gallbladder cancer.
Overview
KEYNOTE-158 (NCT02628067) is Merck's multi-cohort phase 2 of pembrolizumab 200 mg every three weeks in advanced solid tumours. Its biliary adenocarcinoma cohort enrolled 104 patients with incurable gallbladder or bile duct cancer (ampulla of Vater excluded) that had progressed after standard treatment, regardless of PD-L1 status. Objective response by independent central review was 5.8 percent (6 of 104; 95 percent confidence interval 2.1 to 12.1), median duration of response was not reached (range 6.2 to more than 26.6 months), and median overall and progression-free survival were 7.4 and 2.0 months; response was 6.6 percent in PD-L1 expressers and 2.9 percent in non-expressers. Grade 3 to 5 treatment-related adverse events occurred in 13.5 percent with one grade 5 renal failure. The companion KEYNOTE-028 cohort (24 PD-L1-positive patients) responded in 13 percent. The same trial's mismatch-repair-deficient and tumour mutational burden cohorts underpinned the tumour-agnostic FDA approvals of pembrolizumab (2017 and 2020), which are the route to single-agent immunotherapy for the small minority of gallbladder cancers with those features; for the rest, checkpoint blockade works only in combination with gemcitabine and cisplatin (TOPAZ-1, KEYNOTE-966).
- 5.8 out of 100 people had their tumour shrink with Pembrolizumab.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- Median 7.4 months with Pembrolizumab.
- A median is a midpoint: half the people did better than this and half did worse.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- Median 2 months with Pembrolizumab.
- A median is a midpoint: half the people did better than this and half did worse.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Advanced solid tumours in histology-defined and biomarker-defined cohorts, including previously treated advanced biliary adenocarcinoma of the gallbladder or biliary tree (n=104; ampullary excluded): pembrolizumab 200 mg every 3 weeks, single arm. People in a different situation may not see the same effect.
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.
1,609 enrolled.
95% CI 2.1 to 12.1
SourceSimilar pages
not linked directly; found by shared links- TrialAgnostic Therapy in Rare Solid Tumors
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
- TrialTRAP-BTC
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), PD-1, Biliary tract cancer (cholangiocarcinoma).
- TrialChemotherapy Combined With Adebrelimab and Mecapegfilgrastim in Neoadjuvant Treatment of Potentially Resectable BTC
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
- TrialA Study of HRS-4642 Monotherapy or in Combination With Adebrelimab in the Treatment of Advanced Biliary Tract Tumors.
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
- TrialA Single-arm, Multicenter, Exploratory Study of Adebrelimab Combined With Apatinib and Systemic Chemotherapy for Initially Unresectable Biliary Tract Cancer
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
- TrialTesting the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
- TrialEORTC 1607: pembrolizumab with cisplatin and gemcitabine in biliary tract cancer
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.
- TrialOlanzapine for the Management of Cancer Associated Appetite Loss in Patients With Advanced Esophagogastric, Hepatopancreaticobiliary, Colorectal or Lung Cancer
Shares Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups), Biliary tract cancer (all types), Biliary tract cancer (cholangiocarcinoma), Gallbladder cancer.