Baseline variables may predict immunotherapy response in metastatic ccRCC
medwireNews: A number of baseline variables, including age and PD-L1 expression level, may be linked to survival outcomes among people receiving PD-1 or PD-L1 inhibitors for metastatic clear cell renal cell carcinoma (ccRCC), meta-analysis data show.
Memorial Sloan Kettering Cancer Center (MSKCC) risk score and type of sarcomatoid tumor differentiation were also associated with treatment response, note Paul Arora (Cytel Inc, Toronto, Ontario, Canada) and co-investigators. They say that each of “[t]hese baseline factors may help to guide the delivery of anti–PD-1/PD-L1 immunotherapy for metastatic clear cell renal cell carcinoma.”
The meta-analysis focused on subgroup findings from six phase 2 or 3 randomized clinical trials of PD-1 or PD-L1 inhibitors that measured overall survival (OS) or progression-free survival (PFS) among patients with metastatic ccRCC.
The researchers report in JAMA Network Open that, based on data from Checkmate 025, Checkmate 214, and KEYNOTE-426, patients aged 75 years and older had significantly worse OS than those younger than 65 years of age.
They calculated that the ratio of pooled hazard ratios (HRs) for the older versus younger categories was 1.51.
Data from IMmotion150, IMmotion151, KEYNOTE-426, and JAVELIN Renal 101 indicated that PFS was significantly shorter in individuals who had a PD-L1 expression level below 1% versus those who had higher PD-L1 expression. In this case, the team found that the ratio of the HR for PD-L1 below 1% to the HR for PD-L1 at or above 1%, was 1.36.
In addition, the ratio of the HR for PD-L1 below 1% to the HR for PD-L1 at or above 10%, as derived from IMmotion150 and IMmotion151, was a significant 2.21.
For MSKCC risk score, reported in IMmotion150, IMmotion151, and JAVELIN Renal 101, the PFS ratio of HR for an immediate risk score to that of the HR for a poor risk score was a significant 1.62, indicating that “patients in the intermediate MSKCC risk group at baseline had a significantly reduced response to PD-1/PD-L1 inhibitors compared with patients in the poor risk group,” the researchers remark.
The only other variable linked to outcome was sarcomatoid tumor presence, for which Arora et al found that patients without sarcomatoid tumor differentiation had significantly worse PFS than those with sarcomatoid tumors. The ratio of the HR for no sarcomatoid differentiation to that for sarcomatoid differentiation was 1.54, based on data from IMmotion150 and IMmotion151.
The authors conclude that although they identified “subgroups of patients who may have a diminished response to anti–PD-1/PD-L1 therapies […], it is important to recognize that such subgroups may still benefit from PD-1/PD-L1 inhibitors.”
The stress: “Although the efficacy of these immunotherapies may be diminished, such therapies may still be more efficacious than the prior standard therapies within these subgroups.”
In an accompanying commentary, Alice Fan and John Leppert, both from Stanford University School of Medicine in California, USA, say that the “meta-analysis likelihood ratio approach has limitations.”
They point out that “[c]linical decision-making requires information to help clinicians choose the best treatment for an individual patient, rather than the relative likelihood of a patient to respond to PD-1/PD-L1 [inhibitors]” and say that the data should therefore “be interpreted with caution.”
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