Berzosertib Fails to Improve Urothelial Carcinoma PFS

Clinical trials are often used to understand the safety, efficacy, and tolerability of specific treatments. Unfortunately, sometimes the drugs in these studies fail. According to Targeted Oncology, this occurred in a Phase 2 trial evaluating berzosertib in conjunction with cisplatin and gemcitabine (the current standard-of-care chemotherapy treatment) for patients with metastatic urothelial carcinoma. Ultimately, the study sought to understand how adding berzosertib to the treatment regimen would improve progression-free survival (PFS). But researchers discovered that this addition did not actually improve PFS at all. Interested in the full study findings? Take a look at the data published in JAMA Oncology.

Berzosertib

To begin, what exactly is berzosertib? MyCancerGenome describes this treatment as:

an inhibitor of ataxia telangiectasia and rad3-related (ATR) kinase, a DNA damage response kinase, with potential antineoplastic activity. [Berzosertib] selectively inhibits ATR kinase activity, [preventing] DNA damage checkpoint activation, [disrupting] DNA damage repair, and [inducing] tumor cell apoptosis.

In the past, the standard-of-care, or even newly attempted combination treatments, have not been extremely effective in patients with metastatic urothelial carcinoma. Thus, a novel therapeutic option is needed. For this reason, researchers believed berzosertib could improve survival rates, cause tumor cells to die, improve the efficacy of the current standards-of-care, and benefit patients.

Within this particular study, approximately 87 patients were enrolled. Researchers wanted to evaluate:

  • How many issues there were with toxicity
  • Potential response predictors
  • Overall response and survival rates
  • Progression-free survival

Patients received either chemotherapy as a singular therapy or in conjunction with berzosertib for six cycles. Findings included:

  • The median progression-free survival was eight months for both groups. Thus, the addition of berzosertib did not improve PFS at all.
  • Those receiving just chemotherapy had longer survival rates than those treated with berzosertib. For example, the group treated with berzosertib had a median overall survival rate of 14.4 months, compared to 19.8 months in the chemotherapy group. Overall response rate (complete and partial response) was also higher in the group treated with chemotherapy alone.
  • 91% of those treated with chemotherapy and berzosertib experienced moderate-to-severe adverse reactions, compared to 66% of those taking chemotherapy alone. These included hematological toxicities, thrombocytopenia (low platelet count), and neutropenia (low white blood cell count).

Urothelial Carcinoma

Also known as bladder cancer, urothelial carcinoma occurs when cancerous cells form in the urothelial cells, which line the bladder. Urothelial carcinoma may also occur in the urethra and renal pelvis. As these cells proliferate, they cause a tumor to form. Risk factors include smoking tobacco, being Caucasian, being male, having a history of chronic bladder infections or bladder cancer, age (55+), or chemical exposure. Symptoms associated with urothelial cancer include:

  • Hematuria (blood in the urine)
  • Painful urination
  • Unintended weight loss
  • Appetite loss
  • Changes in bladder habits, such as urinary frequency
  • Swollen feet
  • Fatigue and/or general malaise
  • Pain on one side in the lower back
  • Bone pain

Learn more about urothelial carcinoma.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

Share this post

Share on facebook
Share on twitter
Share on linkedin
Share on pinterest
Share on print
Share on email