Pembrolizumab for advanced urothelial carcinoma: exploratory ctDNA biomarker analyses of the KEYNOTE-361 phase 3 trial.

Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance. To identify potential biomarkers of response, we retrospectively evaluated association of pre- and post-treatment ctDNA with clinical outcomes in a subset of patients who received pembrolizumab (n = 130) or chemotherapy (n = 130) in KEYNOTE-361. Baseline ctDNA were associated with best overall response (BOR;P = 0.009), progression-free survival (PFS;P < 0.001), and overall survival (OS;P < 0.001) for pembrolizumab, but not chemotherapy (all, P > 0.05). Chemotherapy induced larger ctDNA decreases from baseline to treatment cycle 2 than pembrolizumab; however, change with pembrolizumab (n = 87) were more associated with BOR (P = 4.39 × 10-5) and OS (P = 7.07 × 10-5) versus chemotherapy (n = 102; BOR: P = 1.01 × 10-4; OS: P = 0.018). Tumor tissue-informed versions of ctDNA change metrics were most associated with clinical outcomes but did not show statistically significant independent value for explaining OS beyond radiographic change by RECIST v1.1 when jointly modeled (pembrolizumab P = 0.364; chemotherapy P = 0.823). These results suggest distinct patterns in early ctDNA changes with immunotherapy and chemotherapy and differences in their association with long-term outcomes, which provide preliminary insights on the utility of liquid biopsies for treatment monitoring in metastatic urothelial cancer. Clinical trial registration: NCT02853305.

The Armed Conflict and the Impact on Patients With Cancer in Ukraine: Urgent Considerations.

On February 24, 2022, a war began within the Ukrainian borders. At least 3.0 million Ukrainian inhabitants have already fled the country. Critical infrastructure, including hospitals, has been damaged. Children with cancer were urgently transported to foreign countries, in an effort to minimize interruption of their life-saving treatments. Most adults did not have that option. War breeds cancer-delaying diagnosis, preventing treatment, and increasing risk. We project that a modest delay in care of only 4 months for five prevalent types of cancer will lead to an excess of over 3,600 cancer deaths in the subsequent years. It is critical that we establish plans to mitigate that risk as soon as possible.

Predictors of pathologic complete response to neoadjuvant treatment in HER2-overexpressing breast cancer: a retrospective analysis using real-world data.

The human epidermal growth factor receptor 2 (ERBB2, HER2 or HER2/neu) is a transmembrane tyrosine kinase receptor that is overexpressed in approximately 20% of breast cancers. The use of the anti-HER2 monoclonal antibodies Pertuzumab and Trastuzumab in association with chemotherapy has achieved a higher percentage of pathologic complete response (pCR) than conventional chemotherapy. The purpose of our study was to identify factors that could affect the therapeutic response of patients with breast cancer and HER2 overexpression treated with cytotoxic chemotherapy plus double HER2 blockade in neoadjuvant setting at Fundación Arturo López Pérez (FALP). A case-control study was designed to evaluate the effect of clinical and histopathological variables on the response to neoadjuvant therapy. Ninety-four women with non-metastatic breast cancer and HER2 overexpression received neoadjuvant combination chemotherapy with Trastuzumab and Pertuzumab at FALP during the period 2017-2020. Seventy percent of patients achieved pCR, and in the group of hormone receptor negative patients, 89% of patients achieved pCR. Different variables were analysed trying to look for clinicopathological predictors of complete response. This study provides us with real-world data on the efficacy of using this treatment combination in our population of HER2-overexpressing breast cancer patients.