Drug-free interval feasible in metastatic RCC
medwireNews: Incorporating a drug-free interval into first-line treatment for metastatic clear cell renal cell carcinoma (RCC) may not be detrimental to patient survival or quality of life, suggest STAR trial data presented at the ESMO Congress 2021.
Janet Brown, from the University of Sheffield in the UK, explained that STAR is a phase 2/3 trial in which patients with newly diagnosed metastatic (RCC) from 60 centers across the UK were randomly assigned to receive a conventional continuation strategy (CCS; n=461) or a drug-free interval strategy (DFIS; n=458) for treatment with sunitinib or pazopanib.
Participants initially received 24 weeks of treatment in 6-week cycles. At week 24, individuals in the CCS arm continued with treatment until disease progression, when they stopped treatment.
Those in the DFIS arm stopped treatment at week 24 until radiologic evidence of disease progression, when they restarted treatment. Further treatment breaks were allowed depending on disease response and patient or clinician choice, and the strategy continued until intolerance, progression while on treatment, or death.
In the DFIS arm, 248 patients continued with the trial past 24 weeks and had a median treatment break length of 87 days. Just over half (51.2%) of these participants started one break, 15.3% started two, and 27.4% started three or more breaks, with a maximum of nine.
Brown reported that, in the intention-to-treat (ITT) analysis, median overall survival (OS) was 28 months in the CCS arm and 27 months in the DFIS arm, which corresponded to a hazard ratio (HR) of 0.97 with a lower 95% confidence interval (CI) boundary of 0.83.
In the per-protocol (PP) analysis, which included 453 participants in the CCS group and 418 in the DFIS group, the median OS durations were the same, but the HR was 0.94 with a lower 95% CI boundary of 0.80.
This meant that non-inferiority with DFIS relative to CCS was not met, because the lower CI needed to be above the predefined level of 0.812, equivalent to a 7.5% or lower difference in OS, in both analyses.
However, Brown pointed out that the “analysis had reduced power due to the trial stopping before the required number of events was reached for 80% power.” The actual power was around 77% “and we know that we can certainly say that it equated to less than 7.7% survival difference in that PP arm,” she remarked.
For the co-primary endpoint of quality-adjusted life years (QALYs), both the ITT and PP analyses met the criteria for non-inferiority, indicating that there was a 10% or lower difference in QALYs between the two arms.
Furthermore, at 2 years, the DFIS was associated with cost savings, driven by reduced treatment cost, of £6954 (US$ 9498, € 8099) per participant.
Brown also told delegates that fewer participants in the DFIS arm reported treatment-related serious adverse events (SAEs) after week 24 than in the CCS arm, at 9.4% versus 11.7%. Moreover, 39.0% of the SAEs reported from week 24 onwards occurred in the DFIS arm whereas 61.0% occurred in the CCS arm.
She concluded: “Treatment breaks were acceptable to patients and clinicians, were not detrimental to overall survival or quality of life and had significant cost savings.”
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