Which sequence is most efficacious for PD-1/L1 inhibitors, carboplatin-based chemotherapy?

Cisplatin-ineligible patients with metastatic urothelial carcinoma treated with PD-1/L1 inhibitor followed by carboplatin-containing chemotherapy show similar overall survival (OS) with those treated with the reverse sequence, a study has found.

“Current first-line treatment options in patients with metastatic urothelial carcinoma unfit to receive cisplatin containing chemotherapy include PD-1/L1 inhibitors and carboplatin-containing chemotherapy,” the authors said. “However, the optimal sequencing of these therapies remains unclear.”

This multicentre retrospective study addressed this issue by analysing 146 consecutive cisplatin-ineligible patients with metastatic urothelial carcinoma treated with first line carboplatin-containing chemotherapy followed sequentially by second line PD-1/L1 inhibitor (n=34; group 1) or the reverse order (n=103; group 2).

The authors collected data on patient demographics, objective response, time to treatment failure for first- and second-line therapy, interval between end of first-line and initiation of second-line treatment, and OS. They also conducted multivariable analysis to examine the association of sequencing on OS.

Of the patients (median age, 72 years), 76 percent were men and 18 percent had liver metastasis. The objective response rates were higher with carboplatin-containing chemotherapy (45.6 percent first line and 44.2 percent second line) compared to PD-1/L1 inhibitors (9.3 percent first line and 21.3 percent second line).

Furthermore, multivariate analysis revealed no association between treatment sequence and OS (hazard ratio, 1.05; p=0.85). The only factor significantly associated with OS was metastasis site (p=0.002).