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How Real-World Data Helps Explore Alternative Dosing for Colorectal, Pancreatic Cancer Therapy

Despite recent advances in cancer therapeutics, side effects remain a big concern as they can impede the optimal delivery of effective therapy.  As a result, optimizing drug dosing and administration schedules is incredibly important to minimize side effects and improve compliance. But exploring alternatives to the standard of care can be challenging, especially in the absence of definitive clinical trial data to guide real-world practice.  Nonetheless, practicing clinicians, when faced with toxicity issues, have had to develop tailored approaches to maximize therapeutic exposure.  

High-quality real-world data (RWD) sets can provide researchers with the necessary insight they need to identify novel care patterns, observe relevant endpoints, and modify medication dosing schedules.

At Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C., a team of clinical researchers partnered with COTA to do just that.  

The combined team, which presented its findings at the 2023 ASCO Gastrointestinal Cancers Symposium in San Francisco, was interested in investigating how a different approach to maintenance capecitabine (cape) dosing for stage IV colorectal (CRC) and pancreas cancer (PC) and locally advanced PC might improve outcomes.

Using COTA-generated RWD and real-world evidence (RWE), the researchers were able to recommend a more patient-friendly dosing schedule as a viable alternative for individuals who struggle with the current standard dosing plan without sacrificing efficacy. 

What happened in the study?

Cape is an oral fluoropyrimidine (FP) often used as maintenance therapy for CRC and PC. Currently, the standard FDA-approved dosing schedule for this drug is twice daily for 14 days followed by 7 days off, out of a 21-day cycle.  

Unfortunately, this schedule can be difficult for patients to follow and has been known to produce toxicities, including painful skin swelling and blistering from hand-foot syndrome

Clinicians at MedStar and the Georgetown Lombardi Cancer Center wanted to know if a “continuous” dosing schedule, where cape is taken twice daily Monday through Friday with a treatment break on Saturday and Sunday, could be equally effective without the unwanted side effects. They worked with COTA to develop a customized real-world data set of patients within their institution who received the continuous dosing regimen. Together, the two organizations established endpoints of interest, including dose adjustments and reasons for and rates of treatment discontinuation. 

The results showed that the continuous dosing regimen produced outcomes comparable to that of the standard 21-day cycle, with relatively few patients changing from the continuous dosing to other schedules (11.4% for pancreatic cancer patients and 9.4% for colorectal cancer patients). Progression-free survival (PFS) estimates were also comparable to estimates previously reported in first-line maintenance studies in CRC and PC that used the standard FDA-approved.

The most common reason for dose schedule change was toxicity from the drug, while the most common reason for discontinuing cape therapy was progression of disease.

With similar results to the established dosing schedule, the researchers felt confident in recommending the continuous dosing strategy as a standard maintenance regimen for patients with applicable disease states.

Why this research is important?

The study not only demonstrated that patients with CRC and PC have an alternative option to an established treatment regimen, but it also highlighted the utility of RWD for bringing clarity to real, tangible issues in patient care and providing meaningful insight regarding optimal treatment approaches for complex, serious cancers.

This collaboration is a valuable case study for how to leverage RWD within innovative clinical research. COTA worked closely with the clinical team at MedStar from beginning to end, first abstracting a fit-for-purpose custom data set, then performing the data analysis, and finally submitting the findings to be shared with peers from across the industry.

It demonstrates RWD’s ability to answer pressing questions about care that is already taking place in clinical practice – a necessary complement to RWD’s established role in the drug development process.

We are proud to work with institutions like MedStar and many others to contribute to the thriving conversation around how to improve cancer experiences and outcomes for patients.  

The COTA team is excited to share our work with attendees at the ASCO GI Cancers Symposium and the broader oncology community. If you would like to learn more about how RWD can unlock insights in your institution, connect with COTA here.