Immune-Related Adverse Effects Linked to Longer Survival With Pembrolizumab in Metastatic Urothelial Carcinoma

Patients with metastatic urothelial carcinoma who received pembrolizumab achieved prolonged median progression-free and overall survival after experiencing an immune-related adverse effect.

Immune-related adverse effects (irAEs) may serve as a prognostic marker for progression-free survival (PFS) and overall survival (OS) in patients with metastatic urothelial carcinoma (mUC) who are receiving pembrolizumab (Keytruda), according to findings presented at the 2022 AUA Annual Meeting.

Ultimately, patients who experienced an irAE while receiving pembrolizumab achieved a median PFS of 28 months (95% CI, 11.7-not reached [NR]) compared with 5.4 months (95% CI, 4.0-8.9) among those who did not experience such an event (P <.0001). Furthermore, the median OS among patients who experienced an irAE was 44.3 months (95% CI, 15.9-44.3; P = .0002) compared with 10.4 months (95% CI, 6.9-19.6) among those who did not (P = .0002).

“PFS was significantly longer in patients with irAEs than [in those] without irAEs,” Kazutaka Nakamura, Department of Urology, Tokiwakai Jyoban Hospital, said in a poster presentation of the findings. “In addition, OS was also significantly longer in patients with irAEs than [in those] without irAEs.”

Study authors noted that the relationship between irAE occurrence and disease prognoses in patients undergoing immune checkpoint inhibition has been observed across various cancer types. Furthermore, multiple studies have reported a positive relationship between irAE incidence and favorable prognoses in patients with mUC receiving pembrolizumab. However, there remains insufficient evidence regarding the prognostic impact of irAEs in this patient population.

Therefore, investigators conducted a retrospective analysis of 95 patients with mUC who received treatment with pembrolizumab as second-line or later-line therapy between January 2018 and February 2022. Patients received pembrolizumab at a dose of either 200 mg every 3 weeks or 400 mg every 6 weeks. Evaluable patients were classified according to their irAE development. Median PFS, OS, overall response rate (ORR), and disease control rate (DCR) were analyzed once the patients began treatment.

Among the 95 evaluable patients, 31 experienced an irAE (32%). Among these patients, a total of 43 irAEs occurred. Notably, there was a significant difference in ECOG performance status greater than 0 between those who did and did not experience an irAE (32% vs 56%, respectively; P =.0282).

At a median follow-up of 15.1 months (interquartile range, 6.1-22.9), 62 patients (65%) had experienced disease progression and 52 (55%) had died.

Overall, univariate and multivariate analysis demonstrated that irAEs is an independent factor contributing to PFS (HR, 0.33; 95% CI, 0.17-0.62; P = .0006). Poor performance status greater than 0 (HR, 2.06; 95% CI, 1.22-3.46; P = .0065) and metastases across multiple organs (HR, 1.75; 95% CI, 1.04-2.94; P = .0343) were also predictive factors for PFS.

Similarly, these factors were also found to be independent factors for OS as well. The hazard ratio for irAEs was 0.32 (95% CI, 0.16-0.66; P = .0018) compared with 2.83 for poor performance status greater than 0 (95% CI, 1.59-5.05; P = .0004), 2.04 for modified Glasgow prognostic score greater than 0 (95% CI, 1.09-3.84; P = .0267), and 1.90 for multiple metastatic organs (95% CI, 1.07-3.39; P = .0288).

Lastly, patients who experienced irAEs achieved significantly higher overall response rates than those who did not experience these events (35% vs 9%, respectively; P = .0019). The difference in disease control rates were significant as well (61% vs 21%, respectively; P = .0002).

“This multi-institutional study showed that [the] presence of irAE[s] was significantly associated with PFS, OS, ORRs, and DCRs in patients [with mUC] treated with pembrolizumab,” the study authors concluded. Moving forward they noted irAE occurrence may be used as a surrogate prognostic factor for pembrolizumab.

Reference

Nakamura K, Ishiyama Y, Nemoto Y, et al. Association between immune-related adverse events and survival of patients with metastatic urothelial carcinoma treated with pembrolizumab. Presented at: 2022 AUA Annual Meeting; May 13-16; New Orleans, LA. Abstract MP03-19. https://bit.ly/3sA2KIA