Immune-linked adverse activities associated with enhanced pembrolizumab outcomes in urothelial carcinoma

Conclusions offered at the 2022 AUA Once-a-year Meeting exhibit that immune-related adverse occasions (irAEs) strengthen survival and development-absolutely free survival of pembrolizumab (Keytruda) in individuals with transitional cell carcinoma (mUC). It indicates that it may perhaps be a marker.

People who professional irAE all through pembrolizumab obtained a median development-absolutely free survival (PFS) of 28 months (95% CI, 11.7-not arrived at). [NR]) In comparison to 5.4 months (95% CI, 4.-8.9) amongst individuals who did not encounter these an celebration ()P <.0001). In addition, median overall survival (OS) for patients who experienced irAE was 44.3 months (95% CI, 15.9-44.3 P Compared to 10.4 months (95% CI, 6.9-19.6) among those who did not (= .0002) (P = .0002).

“PFS was significantly longer in irAE patients [in those] No irAE, “said Kazutaka Nakamura, Department of Urology, Jobankai Joban Hospital, in a poster presentation of the survey results. “In addition, OS was significantly longer in patients with irAE. [in those] No irAE. “

The authors of the study point out that the relationship between the development of irAE and the prognosis of the disease in patients undergoing immune checkpoint inhibition has been observed in different types of cancer. In addition, multiple studies have reported a positive relationship between irAE incidence and good prognosis in mUC patients receiving pembrolizumab. However, there remains insufficient evidence regarding the prognostic effects of irAE in this patient population.

Therefore, the researchers conducted a retrospective analysis of 95 mUC patients treated with pembrolizumab as second-line or late-stage treatment between January 2018 and February 2022. Patients received pembrolizumab at doses of 200 mg every 3 weeks or 400 mg each time for 6 weeks. Evaluable patients were classified according to the onset of irAE. Once the patient started treatment, median PFS, OS, overall response rate (ORR), and disease control rate (DCR) were analyzed.

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

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

Overall, univariate and multivariate analysis showed that irAE 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) was also a predictor of PFS.

Similarly, it turns out that these factors are also independent factors of the OS. The hazard ratio for irAE is 0.32 (95% CI, 0.16-0.66 P = .0018) Compare with 2.83 if performance status is greater than 0 (95% CI, 1.59-5.05 P = .0004), 2.04 (95% CI, 1.09-3.84 P = .0267), and 1.90 for multiple metastatic organs (95% CI, 1.07-3.39 P = .0288).

Finally, patients who experienced irAE achieved significantly higher overall response rates than those who did not experience these events (35% vs. 9%, respectively). P = .0019). Differences in disease control rates were also significant (61% vs. 21%, respectively). P = .0002).

“This multicenter study is [the] Existence of irAE[s] Significantly associated with patient PFS, OS, ORR, and DCR [with mUC] He was treated with pembrolizumab, “the study authors conclude. In the future, they pointed out that the development of irAE may be used as a surrogate prognostic factor for pembrolizumab.

reference

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1. Nakamura K, Ishiyama Y, Nemoto Y, etc. Relationship between immune-related adverse events and survival of patients with metastatic urothelial cancer treated with pembrolizumab. Announcement location: 2022 AUA Annual Meeting. May 13-16. New Orleans, Louisiana. Abstract MP03-19.

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