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In 2021, when Gilead’s clinical development team and research collaborators sat down to plan clinical trials for two different types of metastatic triple-negative breast cancer (mTNBC), the stakes were high. Gilead set out to answer the question of whether its therapy could be proven safe and efficacious in earlier lines of treatment for mTNBC patients.
A key question for the team was “How to solve the clinical unmet needs earlier in the treatment landscape that exist for these patients, while best serving all the patients in the study?”.
TNBC is the most aggressive type of breast cancer and approximately 50% of patients receiving first-line treatment will never receive a second line of therapy. The rapidly progressive nature of mTNBC added additional stakes as the team grappled with a key decision of whether the trials should include a crossover option.
“We know cancer progresses quickly and that our treatment could be an option for people, so it was important to design the trial keeping these important elements in mind,” says Catherine Lai, Executive Director and Global Development Lead of Clinical Research.
The crossover option would enable a patient to receive a standard of care second-line mTNBC therapy once their cancer progressed on the control treatment.
Christine Hodgdon is living with metastatic breast cancer and is Executive Director of GRASP (Guiding Researchers and Advocates to Scientists Partnerships). She explains how many of the mTNBC patients she works with are desperate for more novel treatment options, but she says there’s sometimes a hesitancy to participate in trials because they may not receive the investigational drug. “Crossover could mitigate one reason patients may hesitate to join a clinical trial,” she says.
However, a crossover design comes with some drawbacks. It is much harder to calculate overall survival, an endpoint that can indicate if the group of participants receiving an investigational therapy lives longer than the group receiving standard therapy in the control arm. This is because, with crossover, everyone in the study — including those who started on the control arm — can ultimately get access to a standard of care option upon progression, making it more difficult to compare overall survival results across treatment arms. Overall survival is valued by health authorities, payers, providers and patients.
Ultimately, by approaching the decision from the perspective of the clinical trial participants, Catherine and the team decided that a crossover trial option should happen, even if it could make the trial more challenging.
Dr. Javier Cortés, Head of the International Breast Cancer Center in Spain and principal investigator of one of the clinical trials believes including crossover in the trials was the most patient-centric option in this first-line mTNBC study.
“I really congratulate everyone that understands, in this trial, crossover is essential because we optimize the needs of patients enrolling in our study,” Javier says.
When data from the trials were announced last year at the annual meetings of the American Society of Clinical Oncology and the European Society for Medical Oncology, the significance of the trials’ crossover design was recognized.
Catherine notes how patient-centered trials do not always include crossover options because a different population of patients may be best served by other clinical trials or have different treatment pathways.
“If you have patients as your north star, and make sure the results are meaningful to them, at the end of the day, that’s the conviction to have,” Catherine concludes.