Clinical course of patients with renal cell carcinoma or urothelial carcinoma who had stable disease as an initial response to a PD-1 or PD-L1 inhibitor

Background: About 17%-34% of patients with non-prostatic genitourinary (GU) cancer had stable disease (SD) as their best response to programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. However, most efficacy studies of PD-1/PD-L1 inhibitors are focused on the response and its durability. Little is known about patients' clinical outcomes with SD as their initial response to PD-1/PD-L1 inhibitors.

Methods: We retrospectively reviewed the clinical outcomes of patients with renal cell carcinoma (RCC) (n = 102) and urothelial carcinoma (UC) (n = 101) treated with PD-1/PD-L1 inhibitors. The duration of SD (DoSD) was calculated for patients who had SD as their best response and was defined from the time of SD to radiologically confirmed progressive disease (PD) or death.

Results: Fifty-five patients (27.1%) had SD as the initial response. Among them, 10 patients (18.2%) achieved a response on subsequent assessments. With a median follow-up duration of 15.2 months, the median DoSD was 8.5 months (range: 3.2-13.8), which was significantly different according to the disease; 9.4 months in RCC and 2.3 months in UC (p = 0.03). If the disease did not progress in 4 months (long SD subgroup), the DoSD (11.0 months) was comparable to the duration of response (12.9 months) in patients who achieved a complete or partial response to PD-1/PD-L1 inhibitors. In addition to the cancer type, the clinical factors associated with short DoSD were liver metastases (p = 0.003), neutrophil-lymphocyte ratio (NLR) > 4.0 (p = 0.001), and platelet-lymphocyte ratio (PLR) > 194 (p = 0.003).

Conclusion: For RCC patients with SD to PD-1/PD-L1 inhibitors, if there are no liver metastases and NLR/PLR is below the certain level, they would have similar duration of disease control and survival benefit as those who achieve the response.