In this observational prospective study, we provide evidence that HRQoL improved in mPAC patients receiving any first-line chemotherapy treatment in routine clinical practice, particularly in those with poorer HRQoL at treatment start. Mean scores of the QLQ-C30 global scale and pain, appetite, sleep disturbance, nausea, and constipation symptom scales improved throughout the chemotherapy treatment, whereas scores from the EQ–5D questionnaire (dimensions and VAS) remained unchanged. The evolution of HRQoL throughout the first-line treatment, measured using the QLQ-C30 global health status score, was significantly influenced by patients’ PS and treatment response. Baseline QLQ-C30 global health status scores influenced OS and PFS, suggesting a prognostic value for this factor.
In this study, two instruments were used to measure HRQoL: the EORTC QLQ-C30 scale and the EQ–5D. While QLQ-C30 showed good responsiveness and was sensitive to changes in HRQoL throughout the Treatment Period, EQ–5D (questionnaire and VAS) did not reflect any changes in HRQoL. This finding is in line with a previous observational study in patients with mPAC, in which QLQ-C30, but not EQ–5D, enabled to identify changes in HRQoL . In contrast, another clinical trial reported significant changes in the scores of pain symptoms using EQ–5D in patients with advanced pancreatic cancer . To our knowledge, very few studies on mPAC patients used EQ–5D to assess HRQoL, likely because other cancer-specific tools, such as QLQ-C30 and cancer site-specific instruments, are available. In fact, the National Cancer Institute of Canada Clinical Trial Group chose QLQ-C30 as a standard questionnaire in clinical trials . Even though EQ–5D lacked sensitivity, its response rates were slightly higher than those of the QLQ-C30 questionnaire: mean response rate throughout study visits was 79.0% and 76.1% for EQ–5D dimensions and VAS, respectively, and 70.3% for the complete QLQ-C30 questionnaire. The EORTC QLQ-C30 global health status score, used to investigate correlations with baseline PS, treatment response and prognosis, reached a mean response rate of 78.6% throughout the study. While a consensus on acceptable response rates for patient-reported outcomes remains unestablished, a 70–80% response rate can be considered reasonable to good . Although assessing the validity of these questionnaires was out of the scope of our study, the sensitivity observed with the QLQ-C30 questionnaire suggests it is suitable for measuring changes in HRQoL of mPAC patients undergoing first-line chemotherapy.
Despite the importance of assessing HRQoL to evaluate the balance between toxicity and effectivity of chemotherapy, studies focusing on changes in HRQoL of mPAC patients treated with chemotherapy are scarce, heterogeneous, and have often reported conflicting results. Kristensen et al. systematically reviewed 23 clinical trials in advanced pancreatic cancer, which included the assessment of HRQoL as a secondary endpoint. Of the 14 studies reporting changes in HRQoL compared to baseline, five observed an improvement in at least one treatment arm, three observed worsening in at least one treatment arm, and the remaining seven reported no change . Our results, showing a statistically significant 13-point increase in mean QLQ-C30 global health status scores from baseline to Month 6, are in line with the five studies reporting an improvement in HRQoL in the trial setting [7, 9, 27–29]. Likewise, the decrease in pain scores during the Treatment Period in our cohort, which indicates an improvement of this symptom, are in line with the seven studies (out of eight clinical trials reporting on the evolution of pain scores) showing an improvement in pain [9, 28, 30–34]. Even though the mean QLQ-C30 global health status score improved in our study population throughout the Treatment Period, 17% of patients showed only deterioration. Interestingly, patients with worse HRQoL at baseline were more likely to show an improvement throughout the Treatment Period than those with better HRQoL at baseline.
Asides from assessing the evolution of HRQoL in real-life patients receiving first-line chemotherapy, we investigated the prognostic value of baseline HRQoL in our study population. Previous clinical trials and real-life studies have demonstrated that baseline HRQoL and subsequent changes during treatment (global and subscales) are associated with survival of patients with pancreatic cancer [8, 9, 11–14, 35]. Our results confirmed this trend in a real-life setting, with patients scoring ≥50 in the QLQ-C30 global health status scale and showing higher OS and PFS.
Remarkably, besides low QLQ-C30 global health status scores at treatment start, low baseline PS was significantly associated with a greater improvement in HRQoL throughout the treatment. Thus, although QLQ-C30 global health status scores at baseline were lower in patients with poorer PS (18- and 21-point differences compared to patients with better PS for KI and ECOG, respectively), PS scores of both groups of patients were consistent after two months of chemotherapy. Regarding treatment response, patients with stable disease, or partial or complete response had persistently higher QLQ-C30 global health status scores than those who progressed during the first three months of treatment. Of note, HRQoL assessment was restricted to patients receiving first-line treatment, thus gradually reducing the number of patients in the progression subgroup. The observed trend was consistent with data from clinical trials, indicating a relationship between HRQoL and disease progression [3, 5, 6].
In addition to the general limitations of observational designs, such as the uneven sample size across variables due to missing data, the results of this study must be interpreted in the context of the risk of bias associated with a decrease in the study sample over time. This limitation, also observed in previous studies assessing HRQoL , implies that patients who discontinue treatment because of disease progression or death—and, therefore, are likely to have poorer HRQoL—are not followed up any longer. Consequently, the study population is gradually biased towards a better HRQoL as the follow-up progresses. Nevertheless, our overall purpose was to describe the changes in HRQoL during first-line chemotherapy, making it necessary to interrupt follow-up in patients initiating second-line chemotherapy. Future studies investigating the evolution of HRQoL throughout further treatment lines shall follow up patients during larger periods, irrespective of the treatment outcome.