Product information and disease description Place of product in therapy Disease description Burden of Second-line advanced biliary tract cancer

Humanistic burden and health-related quality of life

10 evidence topics · 5 sources

Summary: health-related quality of life in advanced and second-line disease

Robust health-related quality-of-life data in cholangiocarcinoma are sparse, which the authors of a disease primer attribute to low incidence, high lethality, limited trial enrollment until recently, and a historical lack of dedicated measurement tools. The EORTC QLQ-BIL21 was validated in 172 participants with cholangiocarcinoma and 91 with gallbladder cancer and measures eating, jaundice, tiredness, pain, and anxiety symptoms alongside the generic QLQ-C30.

In the second-line setting, the ABC-06 quality-of-life analysis found no difference between arms in time to deterioration of the global health scale (adjusted hazard ratio 0.97, 95% CI 0.48 to 1.97, P = 0.937) and found that adding FOLFOX did not worsen global, physical, social, or symptom scores, whereas the active-symptom-control arm declined across several domains including the EQ-5D utility value, which fell from 0.75 at baseline to 0.62 at month 4. In the first-line setting, neither durvalumab nor pembrolizumab added to gemcitabine and cisplatin worsened patient-reported outcomes: median time to deterioration of global health status or quality of life was 7.4 months versus 6.7 months in TOPAZ-1, and estimates were similar between arms in KEYNOTE-966.

Humanistic burden: sparse quality-of-life evidence in cholangiocarcinoma

“Robust studies and data on the quality of life of patients with CCA are sparse. This paucity of information is due to the low incidence of the disease, its high lethality, the limited number of patients enrolling in clinical trials until very recently, and the lack of dedicated quality-of-life measurement tools.” (opens the source at this quote in a new tab)

Humanistic burden: validated disease-specific instrument

“There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice.” (opens the source at this quote in a new tab)
“This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder.” (opens the source at this quote in a new tab)
“The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.” (opens the source at this quote in a new tab)

Humanistic burden: quality-of-life dynamics from baseline to month 4 in the second-line setting

Measure	Active symptom control, baseline	Active symptom control, month 4	Active symptom control, P value	Active symptom control plus FOLFOX, baseline	Active symptom control plus FOLFOX, month 4	Active symptom control plus FOLFOX, P value
EQ-5D utility value	“0.75”	“0.62”	“0.0309”	“0.77”	“0.70”	“0.6183”
QLQ-C30 Summary score	“77”	“64”	“0.0446”	“79”	“71”	“0.1846”
QLQ-C30 Physical health scale	“74”	“59”	“0.0221”	“78”	“66”	“0.1238”
QLQ-C30 Social function scale	“77”	“61”	“0.0272”	“76”	“65”	“0.1307”
QLQ-C30 Role scale	“71”	“49”	“0.0283”	“76”	“57”	“0.2713”
QLQ-C30 Nausea	“10”	“25”	“0.0009”	“10”	“16”	“0.4495”
QLQ-C30 Pain	“29”	“44”	“0.0323”	“28”	“21”	“0.2089”

Humanistic burden: time to deterioration of global health in the second-line setting

“Exposure to FOLFOX did not have a significant impact on the time to Global Health Scale deterioration (n = 76 participants; 36 patients ASC-alone arm; 40 patients in the FOLFOX arm), with similar TTD in both arms” (opens the source at this quote in a new tab)
“aHR 0.97, 95% CI 0.48-1.97, P = 0.937” (opens the source at this quote in a new tab)
“Addition of FOLFOX to ASC did not appear to induce worsening of the QoL parameters assessed (Table 3) at 4 months of study entry. In contrast, patients in the ASC-alone arm appeared to experience worsening of the EQ-5D utility values and most of the QLQ-C30 scales (including global, physical, social, and role scales), whereas these were stable in the FOLFOX arm.” (opens the source at this quote in a new tab)
“The absence of QoL deterioration with chemotherapy in this frail population highlights the importance of disease control, even in the absence of symptomatic improvement.” (opens the source at this quote in a new tab)

Humanistic burden: endpoint status, questionnaire completion, and compliance in the first-line setting

“Patient-reported outcomes were a prespecified secondary endpoint of the trial, but these analyses were not powered for formal testing.” (opens the source at this quote in a new tab)
“More than 81% of participants in both treatment groups completed both questionnaires at baseline (figure 1). The proportion of participants who completed the questionnaires remained higher than 70% throughout 28 cycles of treatment (figure 1).” (opens the source at this quote in a new tab)

“At week 18, 320 (61.5%) participants in the pembrolizumab arm completed QLQ-C30 with a 93.3% compliance rate (320 out of 343 participants) vs. 315 (60.9%) in the placebo arm with a 95.7% compliance rate (315 out of 329).” (opens the source at this quote in a new tab)

Humanistic burden: baseline symptom burden in the first-line setting

“Mean global health status or QOL scores for participants at baseline were 63·0 (95% CI 60·7–65·3) in the durvalumab group and 65·7 (63·3–68·1) in the placebo group.” (opens the source at this quote in a new tab)
“Symptoms with mean scores greater than 20 in either treatment group were anxiety, fatigue, tiredness, insomnia, pain, appetite loss, weight loss, and abdominal pain (table).” (opens the source at this quote in a new tab)

Humanistic burden: patient-reported outcomes in the first-line setting

“Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]).” (opens the source at this quote in a new tab)
“The adjusted mean change from baseline scores for all patient-reported outcomes did not meet the predefined threshold of an absolute change of 10 points or greater.” (opens the source at this quote in a new tab)
“In a post-hoc analysis, the HR for time to deterioration of global health status or QOL in the durvalumab group compared with the placebo group was 0·95 (0·74–1·24) up to 7 months, and 0·45 (0·22–0·91) after 7 months (figure 2A).” (opens the source at this quote in a new tab)

“Time to confirmed deterioration estimates were also similar between arms, including for global health status/quality of life (median not reached [NR] in the pembrolizumab arm vs. 21.2 months in the placebo arm; hazard ratio [HR] 0.86, 95% CI 0.70-1.07); jaundice (NR vs. NR; HR 1.20, 95% CI 0.94-1.54), and pain (NR vs. NR; HR 0.79, 95% CI 0.59-1.05).” (opens the source at this quote in a new tab)
“For the six prespecified domains, similar results between treatment arms were observed in the LSM change from baseline to week 18 (Table 1), including GHS/QoL (difference = 0.04, 95% CI -2.52 to 2.60; nominal p = 0.98), physical functioning (difference = 1.24; 95% CI -1.42 to 3.90; nominal p = 0.36) and role functioning (difference = 2.68, 95% CI -0.76 to 6.11; nominal p = 0.13).” (opens the source at this quote in a new tab)
“Comparable changes from baseline to week 18 between the two treatment arms were also seen for jaundice (difference = 0.26; 95% CI -1.35 to 1.87; nominal p = 0.75) and pain (difference = -1.87, 95% CI -4.26 to 0.53; nominal p = 0.13) symptom scale scores, as well as EQ-5D-5L VAS (difference = 0.14; 95% CI -2.18 to 2.46; nominal p = 0.91).” (opens the source at this quote in a new tab)
“The PRO endpoints were exploratory and were not powered to provide statistical significance nor adjusted for multiple comparisons, and therefore the results should be interpreted with caution.” (opens the source at this quote in a new tab)

Humanistic burden: deterioration of global health in relation to objective response and survival

“Median time to deterioration of global health status or QOL was longest for participants with a complete or partial response and shortest for participants with progressive disease (appendix p 9), suggesting that response could be associated with improved QOL.” (opens the source at this quote in a new tab)
“The HR for time to deterioration of global health status or QOL after 7 months suggested that the improved overall survival associated with durvalumab, gemcitabine, and cisplatin compared with placebo gemcitabine, and cisplatin could be accompanied by improved QOL.” (opens the source at this quote in a new tab)

Humanistic burden: perspective of a patient and advocate

“All patients, including myself, desire to increase our survival time. However, I came to a point in my journey in which quality of life became more important than the quantity of life, and my fellow patients agree with this sentiment. I came to this decision because my quality of life declined after 2 years of undergoing chemotherapy, and I had no desire to continue.” (opens the source at this quote in a new tab)
“Because there is no proven treatment and minimal options for CCA, patients are willing to try treatments that have no guarantee of working.” (opens the source at this quote in a new tab)