ASCO’s clinical research endeavors are advancing precision medicine and inclusive research, setting new standards for patient care and treatment optimization. Elizabeth Garrett-Mayer, PhD, vice president of the ASCO Center for Research and Analytics (CENTRA) discusses the new CDK4/6 Inhibitor Dosing Strategies Study (CDK Study) and the ongoing Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Tell us about the new dosing strategies for CDK4/6 inhibitors that the CDK Study will investigate.

EGM: The CDK Study aims to explore whether starting treatment at lower doses of ribociclib and palbociclib allows patients, especially those 65 and older with hormone receptor-positive and HER2-negative metastatic breast cancer, to stay on treatment longer than when starting at the FDA-approved doses, without sacrificing clinical benefits. This approach is based on evidence suggesting that lower doses of CDK4/6 inhibitors may still provide the same clinical benefits as higher doses. Given that older patients are more susceptible to side effects that can lead them to stop treatment, this study is essential. It not only aims to optimize dosing strategies but also to enhance patient quality of life by avoiding potential adverse effects.

This research challenges the conventional one-size-fits-all dosing model, potentially leading to more personalized and effective treatment plans for patients with cancer. It underscores the importance of dose optimization in cancer therapy, which could have far-reaching implications for development of more tailored and patient-friendly treatment protocols.

What are the challenges and expectations as the CDK Study moves into the site recruitment phase?

EGM: As we prepare for patient enrollment in fall 2024, our main challenge is to engage a diverse range of practices, ensuring broad patient representation. Our practice recruitment efforts are pivotal to the CDK Study’s success. We urge the oncology community to join this effort to improve treatment strategies for older adults with metastatic breast cancer. We expect the study to shed light on the “start low, go slow” approach often encouraged by patient advocates and to lead to a broader exploration of dosing strategies across different cancer types.

How is the equity, diversity, and inclusion (EDI) focus influencing the study’s design?

EGM: The CDK Study embodies ASCO’s commitment to EDI by including a diverse range of practices and focusing on older patients. Because these patients are often excluded from clinical trials due to concerns of adverse events or tolerance, the safety profiles of drugs often underestimate side effects in this demographic. This approach will help build a comprehensive understanding of their drug tolerance and dosing needs, addressing the under prescription of anticancer agents to older patients.

How has the TAPUR Study expanded our understanding of off-label uses of FDA-approved targeted agents?

EGM: The TAPUR Study, which began enrolling patients in 2016, is a phase II basket trial evaluating the off-label use of FDA-approved targeted anticancer agents. Conceived by Dr. Richard L. Schilsky, ASCO’s chief medical officer at the time, the study enrolls patients with advanced cancers that harbor a target for one of the TAPUR drugs and is a cancer type for which the drug hasn’t been approved. The TAPUR Study enrolls patients at over 250 sites across the U.S., and the majority are community sites. Currently, TAPUR has 16 targeted agents, and has provided 25 treatments to patients since its inception. From a site perspective, this provides an efficient means of access to many promising anticancer drugs through a single clinical trial protocol for patients with advanced cancer who have no other treatment options. From a patient standpoint, it allows access to novel treatments at community sites, avoiding the need for travel to academic centers.

Although off-label uses of targeted agents were occurring, the results were largely anecdotal. Without a systematic approach for collecting data from these uses, it was challenging—if not impossible—to determine which off-label uses were leading to clinical benefit in patients. The TAPUR trial addresses this gap. With over 2,800 patients enrolled, the TAPUR Study has yielded results demonstrating settings in which targeted agents show promise in patients, with tumor response or extended stable disease, and those settings in which they are unlikely to show benefit. While the positive results are encouraging, identifying cohorts with negative results has been valuable by sparing future patients from potentially toxic agents that are unlikely to provide benefit.

With the clinical and genomic data from the TAPUR Study now available, what innovative research directions do you foresee emerging?

EGM: The availability of TAPUR’s data opens up a wealth of opportunities for cancer research. By standardizing genomic information from a variety of testing laboratories, we’ve created a genomic database on all patients in the TAPUR Study. Alongside clinical data, this provides a gold mine of data for researchers.

Although patients are matched to study treatments based on a single marker, the genomic database includes data on many other cancer-related genes, allowing researchers to search for patterns of genomic signatures and clinical outcomes. There are other ways to use the data, including investigations of co-mutations, and relationships between genomic data and other patient characteristics. Analyses addressing these questions have the potential to predict which patients will have a response to certain treatments and to investigate new applications of currently available treatments.

As part of ASCO’s commitment to fostering a collaborative research ecosystem, we’re excited to share these data with our members to foster further exploration of targeted therapies for patients with cancer.

How do these studies advance ASCO's vision for the future of cancer care?

EGM: The TAPUR and CDK Studies were developed when neither the industry nor other research groups were particularly motivated or equipped to undertake such trials. Based on input from our members, ASCO saw these studies as addressing critically important gaps in knowledge aligned with ASCO’s mission. Both the TAPUR Study and the CDK Study evaluate evidence-based personalized treatment approaches that can enhance quality cancer care. These efforts align with our vision of a world where cancer is prevented or cured, and every survivor is healthy.