Immunotherapy shook up bladder cancer treatment

A next-generation immunotherapy from the checkpoint inhibitor class, nivolumab, was found highly effective in patients who had undergone surgery for muscle-invasive urothelial carcinoma (bladder and urinary tract cancer) when used as adjuvant (protective) treatment. These results were announced at the 2021 Genitourinary Cancers Symposium in the CheckMate 274 study.

One of the most important studies of the last 5 years

This clinical trial enrolled patients regardless of tumor PD-L1 status and whether they had received neoadjuvant (preoperative) chemotherapy.

Median disease-free survival was 21 months in patients given adjuvant nivolumab, compared with patients given placebo, in whom it was 10.9 months; an almost twofold difference.

Disease-free survival is the time after surgery until cancer recurs or metastasis occurs. The primary endpoint of this study was selected as "median disease-free survival time."

Not surprisingly, treatment-related side effects were more common with nivolumab, but health-related quality of life was similar to that with placebo.

Nivolumab made oncology history as the first systemic immunotherapy to show a statistically and clinically significant improvement in outcomes when administered as adjuvant therapy to patients with muscle-invasive bladder cancer!

Dr Dean F. Bajorin, who presented the study, said, "These results support nivolumab monotherapy as a new standard in the adjuvant setting for patients with high-risk urothelial cancer after surgical removal of the bladder, regardless of PD-L1 status and previous neoadjuvant chemotherapy".

Details of the CheckMate 274 study

This international phase-3 study recruited high-risk patients who had undergone surgery for muscle-invasive urothelial cancer of the bladder, ureter or renal pelvis; 709 patients were included.

Of the patient group, 20% had tumors originating in the ureter and renal pelvis, while 80% had tumors in the bladder.

Approximately 43% of patients had received cisplatin-based neoadjuvant chemotherapy, and 40% had tumors positive for PD-L1.

Patients were randomly assigned in a double-blind manner to two arms receiving adjuvant nivolumab or placebo for up to 1 year.

At a median follow-up of approximately 20 months, the clinical trial met its primary endpoint, and treatment with nivolumab showed a significant prolongation of median disease-free survival compared with placebo: 21 months and 10.9 months, respectively (hazard ratio, 0.70;  P  <.001).

In subgroup analyses by disease site, patients with bladder tumors were reported to have more with immunotherapy.

The benefit in disease-free survival was greater in patients whose tumors were positive for PD-L1. In PD-L1-positive patients, median disease-free survival was not reached in the nivolumab group because cancer had not recurred in more than half the patients, compared with 10.8 months in the placebo group (HR, 0.53;  P  <.001).

Patients in the nivolumab group had serious (grade 3 or higher) treatment-related side effects (17.9% versus 7.2%), mainly driven by higher rates of increased amylase and lipase levels. However, there was no deterioration in health-related quality of life compared with placebo.

The most common grade 3 or worse treatment-related side effects potentially mediated by the immune system with nivolumab, including two deaths due to treatment-related pneumonia, were diarrhea (0.9%), colitis (0.9%) and pneumonitis (0.9%).

• Related topic: What are the side effects of immunotherapy drugs, and how are they treated?

Dr Bajorin, who presented the research, acknowledged that overall survival and biomarker data would require longer follow-up. The trial had been designed approximately 7 years earlier, and after discussions, disease-free survival time had been selected as its primary endpoint.