Later-line camrelizumab plus nab-paclitaxel produced durable responses in platinum-treated advanced urothelial carcinoma.
Camrelizumab combined with nab-paclitaxel (Abraxane) produced a median progression-free survival (PFS) of 4.66 months (95% CI, 4.13-8.50) and a median overall survival (OS) of 15.70 months (95% CI, 12.17-not reached [NR]) in patients with previously treated advanced urothelial carcinoma (aUC), according to findings from a multicenter phase 2 study (CTR2000033820) published in Cancer Communications.¹
In the full analysis set (n = 60), the objective response rate (ORR) was 37.04% (95% CI, 24.29%-51.26%), including 4 complete responses (CRs; 7.41%) and 16 partial responses (PRs; 29.63%), with a disease control rate (DCR) of 68.52% (95% CI, 54.45%-80.48%). In the per-protocol set (n = 49), the median PFS was 6.45 months (95% CI, 4.30-9.98) and the median OS was 17.98 months (95% CI, 15.44-NR), with an ORR of 40.81% and a DCR of 73.46%.
Between June 12, 2020, and April 1, 2024, 90 patients were screened and 60 were enrolled at 2 centers in China. Eligible patients were 18 years or older with aUC, an ECOG performance status of 0 to 2, creatinine clearance of at least 30 mL/min, and at least 1 prior platinum-based systemic therapy; prior immune checkpoint inhibitor (ICI) treatment was permitted, but prior taxane treatment was excluded.
Patients received camrelizumab at 200 mg intravenously on day 1 plus nab-paclitaxel at 125 mg/m² on days 1 and 8 of each 21-day cycle, with stepwise nab-paclitaxel dose reductions to 100 mg/m² and 75 mg/m² permitted for toxicity; camrelizumab could continue for up to 24 months. The primary end point was PFS, with secondary end points of OS, ORR, DCR, and safety.
At baseline, the median age was 62.5 years (IQR, 55.0-67.0), 73.33% of patients were male, 73.33% had upper tract urothelial carcinoma (UTUC), and 28.33% had received prior ICI-based therapy.
Any-grade treatment-related adverse effects (TRAEs) occurred in 98.33% of patients (n = 59 of 60), with grade 3/4 TRAEs in 51.67% (n = 31 of 60). The most frequent any-grade TRAEs were leukopenia (55.00%), neutropenia (51.67%), alopecia (48.33%), and peripheral neuropathy (48.33%); reactive cutaneous capillary endothelial proliferation, a camrelizumab-associated toxicity, occurred in 35.00% of patients. One patient discontinued treatment because of immune-related pneumonia, and no grade 5 events were reported.¹
In subgroup analyses, prior ICI-based therapy was associated with inferior PFS on both univariable (HR, 2.74; 95% CI, 1.45-5.17; P = .002) and multivariable analysis (HR, 2.50; 95% CI, 1.21-5.20; P = .013), without a corresponding OS difference. In exploratory analyses of 32 patients with pretreatment serum biomarker data, elevated CD25, IGFBP2, and IL-6 levels were associated with worse response. Using median levels as cutoffs, low CD25 was associated with superior PFS (HR, 0.26; 95% CI, 0.11-0.63; P = .003) and OS (HR, 0.25; 95% CI, 0.09-0.75; P = .013), and low IGFBP1 was associated with superior OS (HR, 0.25; 95% CI, 0.08-0.78; P = .017).
Among 12 patients with targeted gene sequencing data, alterations in KMT2D, TP53, and AR were most frequent (each in more than 30% of patients), while alterations in PIK3C2B and PIK3CA occurred exclusively among responders.
The authors concluded that camrelizumab plus nab-paclitaxel demonstrated modest antitumor activity and acceptable tolerability in previously treated aUC, including in patients with UTUC and those previously exposed to ICIs, and stated that larger, multicenter randomized trials are needed to validate these findings.
