Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Gemcitabine and cisplatin plus an immune checkpoint inhibitor

7 evidence topics · 5 sources

ESMO recommendation: first-line chemoimmunotherapy

“Cisplatin–gemcitabine–durvalumab and cisplatin–gemcitabine–pembrolizumab are recommended as first-line therapy [I, A].” (opens the source at this quote in a new tab)
“Cisplatin–gemcitabine combined with either pembrolizumab or durvalumab is a viable option for first-line treatment.” (opens the source at this quote in a new tab)
“At present, there are no discernible clinical, biochemical or molecular biomarkers, nor any notable differences in efficacy or toxicity, favouring one immune checkpoint inhibitor over the other.” (opens the source at this quote in a new tab)

Durvalumab plus gemcitabine and cisplatin: TOPAZ-1 phase 3 results

“Patients with advanced biliary tract cancer have a poor prognosis, and first-line standard of care (gemcitabine plus cisplatin) has remained unchanged for more than 10 years.” (opens the source at this quote in a new tab)
“The hazard ratio for overall survival was 0.80 (95% confidence interval [CI], 0.66 to 0.97; P=0.021).” (opens the source at this quote in a new tab)
“The estimated 24-month overall survival rate was 24.9% (95% CI, 17.9 to 32.5) for durvalumab and 10.4% (95% CI, 4.7 to 18.8) for placebo.” (opens the source at this quote in a new tab)
“Objective response rates were 26.7% with durvalumab and 18.7% with placebo.” (opens the source at this quote in a new tab)

Durvalumab plus gemcitabine and cisplatin: TOPAZ-1 median survival, response, and safety

“Median overall survival was 12.8 months (95% CI, 11.1 to 14.0) in the durvalumab group and 11.5 months (95% CI, 10.1 to 12.5) in the placebo treatment group (Fig. 1A).” (opens the source at this quote in a new tab)
“Median progression-free survival was 7.2 months (95% CI, 6.7 to 7.4) with durvalumab and 5.7 months (95% CI, 5.6 to 6.7) with placebo (Fig. 1B).” (opens the source at this quote in a new tab)
“The rate of immune-mediated adverse events was 12.7% with durvalumab and 4.7% with placebo.” (opens the source at this quote in a new tab)
“Of the full analysis set, the number of patients who received one or more regimens of subsequent anticancer therapy post-discontinuation was 145 (42.5%) in the durvalumab group and 170 (49.4%) in the placebo group (Table S4).” (opens the source at this quote in a new tab)

Outcome	Durvalumab plus gemcitabine and cisplatin	Placebo plus gemcitabine and cisplatin
Objective response rate, no. (%)	“91 (26.7)”	“64 (18.7)”
Disease control rate, no. (%)	“291 (85.3)”	“284 (82.6)”
Median duration of response (IQR), mo	“6.4 (4.6–17.2)”	“6.2 (3.8–9.0)”
Median time to response (IQR), mo	“1.6 (1.3–3.0)”	“2.7 (1.4–4.1)”

Adverse events, no. (%)	Durvalumab plus gemcitabine and cisplatin (n=338)	Placebo plus gemcitabine and cisplatin (n=342)
Grade 3 or 4, any cause	“256 (75.7)”	“266 (77.8)”
Serious, any cause	“160 (47.3)”	“149 (43.6)”
Leading to discontinuation of any study treatment	“44 (13.0)”	“52 (15.2)”
Leading to death	“12 (3.6)”	“14 (4.1)”
Treatment-related, grade 3 or 4	“212 (62.7)”	“222 (64.9)”

Pembrolizumab plus gemcitabine and cisplatin: KEYNOTE-966 phase 3 results

“Median overall survival was 12·7 months (95% CI 11·5-13·6) in the pembrolizumab group versus 10·9 months (9·9-11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72-0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]).” (opens the source at this quote in a new tab)
“At the first interim analysis, 153 (29% [95% CI 25 to 33]) of 533 participants in the pembrolizumab group and 153 (29% [25 to 33]) of 536 participants in the placebo group had a complete or partial response (table 2).” (opens the source at this quote in a new tab)
“Median duration of response was 9·7 months (95% CI 6·9 to 12·2) in the pembrolizumab group and 6·9 months (5·7 to 8·2) in the placebo group.” (opens the source at this quote in a new tab)

Subsequent anticancer therapy after first-line gemcitabine and cisplatin plus an immune checkpoint inhibitor

“Median (95% CI) time to first SAT was longer for participants in the durvalumab arm (18.7 [13.2–42.2] months) vs. the placebo arm (12.3 [11.3–24.1] months) (HR 0.92; 95% CI 0.75–1.13; Fig. S2).” (opens the source at this quote in a new tab)
“In the small number of participants who received targeted therapies, the mean time to death or censoring from starting targeted therapy for durvalumab vs. placebo was 21.4 vs. 7.5 months (n = 4 vs. n = 2) with FGFR inhibitors and 11.3 vs. 8.4 months (n = 5 vs. n = 5) with IDH1 inhibitors, when given as subsequent therapy (Fig. S4).” (opens the source at this quote in a new tab)

“253 (47%) of 533 participants in the pembrolizumab group and 261 (49%) of 536 participants in the placebo group had received one or more subsequent anticancer therapies” (opens the source at this quote in a new tab)

Alternative first-line regimens for reduced fitness or organ dysfunction

“Oxaliplatin or carboplatin may be substituted for cisplatin when renal or auditory function is of concern, while gemcitabine plus S-1 can be an option for patients who present with or are susceptible to peripheral sensory neuropathy [II, B]” (opens the source at this quote in a new tab)
“Gemcitabine monotherapy may be used in patients with a PS of 2 [IV, B]” (opens the source at this quote in a new tab)

Grade 3 or 4 adverse events and treatment discontinuations in KEYNOTE-966

“In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4.” (opens the source at this quote in a new tab)
“31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events.” (opens the source at this quote in a new tab)
“Adverse events led to discontinuation of one or more study drugs in 138 (26%) participants in the pembrolizumab group and in 122 (23%) participants in the placebo group; discontinuation of all study drugs occurred in 35 (7%) participants in the pembrolizumab group and 39 (7%) in the placebo group.” (opens the source at this quote in a new tab)