Quality of life in the adjuvant setting. A close look at the ALINA trial (alectinib).
Adjuvant alectinib and Health-Related Quality of life
In this ASCO 2024 series, we provide insights about ASCO 2024 presentations, which is currently taking place between 31th May and 4th June. The annual congress of the American Society of Clinical Oncology is a key event in oncology. Each year, it attracts more than 30,000 attendees in Chicago.
The ALINA trial is taking patients who had ALK-rearranged lung cancer removed and randomizing them between two groups:
2 years adjuvant alectinib.
adjuvant chemotherapy (four 3 weeks cycles).
The trial demonstrated a benefit of alectinib over chemotherapy in terms of disease-free survival (a mix of different outcomes), and was recently FDA approved. However, the trial did not demonstrate an improvement in overall survival with alectinib, as the data are still immature. During ASCO 2024, quality-of-life data from the ALINA trial will be presented.
Several novel agents have been approved in the adjuvant setting in recent years. We analysed the quality-of-life (QoL) data from those trials between 2018 and 2022 and found that in the trials reporting QoL, 90 % had a moderate- to high-risk of bias. In other words, most data were poorly reliable.
Our meta-analysis also found “a non-significant detrimental effect on QoL in the experimental arm”. As you can see in the table, there are many items to consider to determine how much you can rely on the QoL data.
Quality of life in the adjuvant setting
When it comes to quality-of-life assessment, they are several differences between the adjuvant and the metastatic settings:
Questionnaires were originally designed in advanced settings, in patients with cancer-related symptoms.
Therefore, the validity of historical thresholds is questionable.
Financial toxicity remains uncaptured in most trials (see our paper here), this is best explained by the visual below. However, we found the median cost to avert one event in the adjuvant setting was … $1 610 000! (see this paper here)
Back to ALINA: likely a high risk-of-bias in the HRQoL data.
ALINA is an open-label study, which poses an important limitation in how the data are collected and interpreted. Conscious or unconscious biases may affect investigators. Here are the potential identified biases.
risks of performance bias (occurs if the control group is treated with systematic differences): likely due to unblinded design.
detection bias (occurs if the outcome is systematically assessed differently between arms): likely due to unblinded design.
selective reporting bias (occurs if the outcome is systematically assessed differently between arms). This could be partially mitigated by reporting detailed HRQoL results, but transparency about pre-specified outcomes would enhance credibility. Here, these are exploratory outcomes.
missing data: compliance rates look good, however more detailed reporting and addressing how missing data were managed would be crucial for a comprehensive assessment!
Looking forward to seeing the presentation, and the publication!