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

Fluoropyrimidine-Based second-line chemotherapy

7 evidence topics · 8 sources

Guideline recommendation: FOLFOX as the second-line standard of care

“FOLFOX is the standard of care in the second-line setting after cisplatin-gemcitabine-based treatment” (opens the source at this quote in a new tab)
“Irinotecan monotherapy or irinotecan- or liposomal irinotecan-based combination therapy may be considered [III, B]” (opens the source at this quote in a new tab)

“For patients who progressed after frontline therapy and lack actionable alterations, fluoropyrimidine plus oxaliplatin and fluoropyrimidine plus liposomal irinotecan are recommended second-line options, supported by ABC-06 and NIFTY, respectively.” (opens the source at this quote in a new tab)
“The primary endpoint, median OS, was significantly improved with ASC plus FOLFOX over ASC alone (Table 1B). The median PFS was 4.0 months, and the ORR was 4.9% in the FOLFOX arm.” (opens the source at this quote in a new tab)

“FOLFOX is the SoC in the second-line setting after cisplatin–gemcitabine [I, A; ESMO-MCBS v1.1 score: 1; no specific licensed indication in BTC].” (opens the source at this quote in a new tab)
“Second-line ChT has previously been used ad hoc by clinicians with limited knowledge of the magnitude of benefit.” (opens the source at this quote in a new tab)
“Evidence for irinotecan-based therapies is currently limited.” (opens the source at this quote in a new tab)

FOLFOX versus active symptom control: ABC-06 phase 3 results

“Overall survival was significantly longer in the ASC plus FOLFOX group than in the ASC alone group, with a median overall survival of 6·2 months (95% CI 5·4–7·6) in the ASC plus FOLFOX group versus 5·3 months (4·1–5·8) in the ASC alone group (adjusted hazard ratio 0·69 [95% CI 0·50–0·97]; p=0·031).” (opens the source at this quote in a new tab)
“Objective response was observed in four (5%) of 81 patients in the ASC plus FOLFOX group: one (1%) patient had a complete response and three (4%) patients had a partial response.” (opens the source at this quote in a new tab)
“Grade 3–5 adverse events were reported in 42 (52%) of 81 patients in the ASC alone group and 56 (69%) of 81 patients in the ASC plus FOLFOX group, including three chemotherapy-related deaths (one each due to infection, acute kidney injury, and febrile neutropenia).” (opens the source at this quote in a new tab)
“Based on these findings, FOLFOX should become standard-of-care chemotherapy in second-line treatment for advanced biliary tract cancer and the reference regimen for further clinical trials.” (opens the source at this quote in a new tab)

Liposomal irinotecan plus fluorouracil and leucovorin: NIFTY randomized phase 2b trial

“At a median follow-up of 11·8 months (IQR 7·7-18·7), the median BICR-assessed progression-free survival was significantly longer in the liposomal irinotecan plus fluorouracil and leucovorin group (7·1 months, 95% CI 3·6-8·8) than in the fluorouracil and leucovorin group (1·4 months, 1·2-1·5; hazard ratio 0·56, 95% CI 0·39-0·81; p=0·0019).” (opens the source at this quote in a new tab)
“Liposomal irinotecan plus fluorouracil and leucovorin could be considered a standard-of-care second-line therapy for advanced biliary tract cancer.” (opens the source at this quote in a new tab)
“The discordance rate for the date of tumour progression between the investigator and the BICR assessments was 30% (52 of 174; appendix 2 pp 5–8).” (opens the source at this quote in a new tab)
“the possibility of overestimation in the median progression-free survival by BICR assessment cannot be excluded.” (opens the source at this quote in a new tab)

Liposomal irinotecan plus fluorouracil and leucovorin: NALIRICC randomized phase 2 trial

“Median progression-free survival was 2·6 months (95% CI 1·7-3·6) in the nanoliposomal irinotecan group and 2·3 months (1·6-3·4) in the control group (hazard ratio [HR] 0·87 [0·56-1·35]).” (opens the source at this quote in a new tab)
“The addition of nanoliposomal irinotecan to fluorouracil plus leucovorin did not improve progression-free survival or overall survival and was associated with higher toxicity compared with fluorouracil plus leucovorin.” (opens the source at this quote in a new tab)

Liposomal irinotecan plus fluorouracil and leucovorin: NALIRICC overall survival, response, toxicity, and subsequent therapy

“Median overall survival was 6·9 months (95% CI 5·3–10·6) in the nanoliposomal irinotecan group and 8·2 months (5·4–11·9) in the control group (HR 1·08 [0·68–1·72]).” (opens the source at this quote in a new tab)
“The objective response rate was 14% (95% CI 6–27; seven patients) in the nanoliposomal irinotecan group and 4% (1–14; two patients) in the control group.” (opens the source at this quote in a new tab)
“There was a marked difference between groups in the number of severe (grade 3 or worse) adverse events, of which 95, affecting 34 (71%) of 48 patients, were reported for the nanoliposomal irinotecan group, and 57, affecting 24 (50%) of 48 patients, were reported for the control group.” (opens the source at this quote in a new tab)
“Discontinuation of study treatment due to toxicity was reported in five (10%) patients in the nanoliposomal irinotecan group and in one (1%) patient in the control group.” (opens the source at this quote in a new tab)
“After end of study participation, 18 (37%) of 49 patients in the nanoliposomal irinotecan group and 30 (59%) of 51 patients in the control group received subsequent anticancer treatment (appendix p 3). Of note, 21 (70%) of 30 patients from the control group who received subsequent therapies were treated with irinotecan-based regimens.” (opens the source at this quote in a new tab)

Sources of discordance between the NIFTY and NALIRICC results

“Differences in sample size (174 vs. 100), iCCA proportion (64% vs. 43%), ethnicity (Asian vs. White), and more frequent early treatment discontinuations due to toxicity in NALIRICC may have contributed to the discordant results [28].” (opens the source at this quote in a new tab)

Pooled individual patient data from NIFTY and NALIRICC

“Current standard of care for second-line therapy in patients with advanced biliary tract cancer (BTC) is FOLFOX.” (opens the source at this quote in a new tab)
“The nal-IRI plus 5-FU/LV group showed significantly longer median PFS (3.6 months [95% CI 2.7-4.4] vs. 1.8 months [95% CI 1.5-2.6]; hazard ratio 0.65, p <0.001).” (opens the source at this quote in a new tab)
“There was no statistically significant difference in OS (median 8.1 vs. 6.1 months, HR 0.77, p = 0.051).” (opens the source at this quote in a new tab)
“However, nal-IRI plus 5-FU/LV may be considered a viable alternative to second-line FOLFOX for patients of East Asian ethnicity or those deemed unfit for FOLFOX (e.g. due to severe peripheral neuropathy caused by prior platinum-based therapy).” (opens the source at this quote in a new tab)