Abstract
BACKGROUNDThe outcome of patients who progress on front-line immune-based combination regimens (IC) including immune checkpoint inhibitors (CPI) and receive subsequent systemic therapy is unknown.MethodsRetrospective analysis of consecutive patients with clear-cell mRCC who progressed on one of seven clinical trials investigating an IC and received ≥1 line of subsequent VEGFR TKI therapy.ResultsThirty-three patients [median age 57 (37–77), 85% male, 73% ECOG 0] were included. For evaluable patients (N = 28), the best response to first subsequent therapy was 29% partial response, 54% stable disease, and 18% progressive disease. The median PFS (mPFS) for first subsequent therapy was 6.4 months (95% CI, 4.4–8.4); no difference in mPFS by prior type of IC (VEGFR TKI-CPI vs. CPI-CPI) was noted (p = 0.310). Significant AEs were observed in 30% of patients, more frequently transaminitis (9%).ConclusionsVEGFR TKIs have clinical activity in mRCC refractory to IC therapy, possibly impacted by the mechanism of prior combination therapy.
Highlights
Medical treatment for metastatic renal cell carcinoma has expanded considerably from a nonspecific immune approach to targeted therapies against vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin.[1,2,3,4,5] More recently, the survival benefit and subsequent approval of the immune checkpoint inhibitor (CPI) nivolumab, for patients with refractory mRCC has ushered in a new era of research into potential combination approaches to improve outcomes and to potentially overcome resistance.[6]
Among the 41 patients who progressed, 8 patients were excluded: five patients remained on axitinib at an escalated dose after coming off trial with a combination regimen that included axitinib; one patient received nivolumab as first subsequent therapy after immune-based combination regimens (IC) and two patients died before starting subsequent therapy
Twenty-four patients were on combo at time of progressive disease (PD), while four patients were on singleagent VEGFR TKI, three on checkpoint inhibitors (CPI) alone and two other had both IC agents on hold due to toxicity
Summary
Medical treatment for metastatic renal cell carcinoma (mRCC) has expanded considerably from a nonspecific immune approach to targeted therapies against vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin (mTOR).[1,2,3,4,5] More recently, the survival benefit and subsequent approval of the immune checkpoint inhibitor (CPI) nivolumab, for patients with refractory mRCC has ushered in a new era of research into potential combination approaches to improve outcomes and to potentially overcome resistance.[6]. The clinical outcome of patients who receive subsequent systemic therapy is undetermined. To assess the safety and efficacy of subsequent treatments in the post-immunotherapy setting, we conducted a retrospective review of consecutive mRCC patients from two academic centres who had received a prior IC and were subsequently treated with a targeted agent. The outcome of patients who progress on front-line immune-based combination regimens (IC) including immune checkpoint inhibitors (CPI) and receive subsequent systemic therapy is unknown. METHODS: Retrospective analysis of consecutive patients with clear-cell mRCC who progressed on one of seven clinical trials investigating an IC and received ≥1 line of subsequent VEGFR TKI therapy. CONCLUSIONS: VEGFR TKIs have clinical activity in mRCC refractory to IC therapy, possibly impacted by the mechanism of prior combination therapy
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