A clinical trial at The Christie NHS Foundation Trust in Manchester is showing promising results for patients with metastatic breast cancer. Elaine Sleigh, a 42-year-old mother of two diagnosed with triple-negative breast cancer, has seen her tumors decrease by 65% through participation in the PETRA trial.
The PETRA trial is evaluating the efficacy of a combination therapy involving AZD5305, an experimental PARP inhibitor, and Trastuzumab Deruxtecan (T-Dxd). Triple-negative breast cancer is an aggressive form of the disease characterized by rapid growth, limited treatment options, and a poorer prognosis compared to other breast cancer subtypes. The trial offers a potential new avenue for patients who have experienced recurrence and spread of the disease.
Treatment and Response
Elaine Sleigh's journey began in 2021 when she discovered a lump in her armpit. Following an initial course of chemotherapy, a mastectomy, and radiotherapy, the cancer recurred. Subsequent tests revealed cancer cell DNA in her bloodstream, leading to further chemotherapy and immunotherapy. However, the cancer returned again, spreading to her lymph nodes and lungs.
In April 2024, Elaine enrolled in the PETRA trial, receiving a combination of AZD5305 and T-Dxd. AZD5305 is designed to inhibit PARP, a protein involved in DNA repair within cells. By blocking PARP, the drug prevents cancer cells from repairing themselves, leading to cell death. T-Dxd, on the other hand, is a combination of trastuzumab (Herceptin) and deruxtecan, a chemotherapy drug that targets the HER2 protein on breast cancer cells, even in HER2-low expressing cancers.
"We’re really pleased with how Elaine has responded so far to her treatment which is a combination of 2 different drugs," said Dr. Anne Armstrong, consultant oncologist at The Christie and lead investigator of the PETRA trial. "The first is an experimental targeted treatment known as AZD5305 which is a type of PARP inhibitor...The second drug Elaine is receiving is Trastuzumab Deruxtecan (T-Dxd) which is a combination of trastuzumab (Herceptin) and deruxtecan (Dxd), a chemotherapy drug which targets the HER2 protein on breast cancer cells."
Trial Design and Objectives
The PETRA trial, sponsored by AstraZeneca, is a Phase 1/2 study designed to determine the safe and tolerable dose of AZD5305, both as a monotherapy and in combination with other cancer treatments. The trial includes patients with advanced solid tumors, including breast, ovarian, prostate, and pancreatic cancers. The primary objective is to assess the safety and tolerability of AZD5305, while secondary objectives include evaluating its efficacy in combination with other cancer treatments.
Implications for Breast Cancer Treatment
The results observed in Elaine Sleigh's case highlight the potential of PARP inhibitors like AZD5305 in combination with HER2-targeted therapies for treating metastatic breast cancer, particularly in cases where the cancer has recurred or spread. The PETRA trial is ongoing, and further results are anticipated to provide a more comprehensive understanding of the drug combination's efficacy and safety profile across different cancer types. The UK Chief Investigator is Dr Adam Sharp at The Institute of Cancer Research, London and Royal Marsden NHS Foundation Trust.
