Survival Benefit, Neutropenia Risk Influence Third-Line Treatment Preferences for mCRC in Germany and the UK

Metastatic colorectal cancer|

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Physicians’ preferences for third-line treatment options in metastatic colorectal cancer (mCRC) in the United Kingdom (UK) and Germany were primarily influenced by expected improvements in overall survival (OS), 3-month progression-free survival (PFS) rates, and the risk of grade 3 or higher neutropenia, according to findings from a survey shared during the 2025 ESMO Gastrointestinal Cancer Congress.¹ However, respondents indicated a willingness to place less emphasis on potential OS gains in favor of avoiding treatment-related toxicity risk or regimens with a higher treatment burden.

On average, physicians in Germany (n = 81) and the UK (n = 75) most frequently rated OS as the most important of the 8 attributes to improve (Germany, 1.8; UK, 2.0), followed by 3-month PFS rate (3.1; 3.2), grade 3 or higher neutropenia (3.7; 3.8), grade 3 or higher hand-foot syndrome (4.6; 5.5), all-grade diarrhea (4.6; 4.7), and all-grade fatigue (5.5; 5.0). Hypertension less than grade 3 (6.3; 6.2) or mode of administration (5.6; 6.5) were the lowest-ranked attributes in both countries, although mode of administration was ranked higher by UK vs German physicians.

Survey results also showed that a minimum additional OS benefit was required for physicians to accept a 10% increase in treatment-related risks or switch to a less desirable regimen. Physicians in Germany and the UK necessitated a 1.1-month and 1.3-month increase in OS, respectively, to accept treatment with a 10% increase in the risk of grade 3 or higher hand-foot syndrome. Similarly, to accept a twice-daily treatment regimen of 3 oral pills and an intravenous infusion every 2 weeks vs a regimen comprising 2 oral pills once daily, physicians in Germany and the UK required 1.1-month and 2.5-month increases in OS, respectively.

Regarding the management of adverse effects, most physicians in Germany and the UK reported being somewhat or very comfortable managing toxicities such as any-grade diarrhea (91.3%; 85.3%), grade 3 or higher neutropenia (91.4%; 78.7%), and less than grade 3 hypertension (93.8%; 82.7%). Additionally, approximately half of physicians were somewhat or very comfortable managing grade 3 or higher hand-foot disease (61.7%; 61.3%) and any-grade fatigue (48.2%; 60.0%).

“These findings indicate that physicians require survival gains to accept increased toxicity or more burdensome treatment regimens, such as those requiring IV administration” presenting author Ashley Geiger, PhD, associate director of Oncology Patient-Centered Outcomes at Takeda, and coauthors wrote in a poster presentation of the data.“[They also] highlight the importance of accounting for physicians’ preferences when developing new treatments, to support alignment with clinical decision-making and real-world treatment considerations.”

Survey Design and Physician Characteristics

The current third-line or later treatment options for metastatic colorectal cancer (mCRC) are associated with modest survival benefits, typically extending OS by approximately 2 to 3 months. However, the toxicity profiles of these regimens vary significantly, posing challenges in balancing survival gains with treatment-related risks and quality-of-life considerations during clinical decision-making.

To better characterize the factors influencing treatment selection, investigators conducted a survey to assess how specific treatment attributes affect physicians’ preferences for third-line mCRC therapies in Germany and the UK.

The study comprised oncologists and gastroenterologists who had self-reported treating 10 or more patients in the last year. Physicians were recruited through established panels. Of the 156 physicians who completed the survey, the majority were male (Germany, 80.2%; UK, 80.0%). Medical oncologists were the most represented medical specialty across both countries (86.4%; 82.7%) followed by gastroenterologists (22.2%; 20.0%) and radiation oncologists (3.7%; 16.0%). In Germany, 87.7% of physicians surveyed had treated 20 or more patients with mCRC in the last year, and 39.5% had 20 or more patients who mCRC who received third-line treatment in the past year. For UK physicians, these respective percentages were 90.7% and 46.7%.

Upon recruitment, physicians completed a survey of multidimensional thresholding exercises, including 2 attribute ranking exercises and a thresholding exercise consisting of 13 to 15 paired treatment comparison tasks. Treatment attributes were determined according to a targeted review of scientific literature and clinical data, patient engagement, and pilot interviews with both patients and physicians.

In the attribute-ranking exercise, physicians ranked each of the 8 identified attributes in order or most (1st place) to least (8th place) important to improve. In the thresholding exercise, which was constructed according to individual attribute rankings, physicians chose their preferred treatment through a series of paired comparison tasks. Preferences were examined through the ranking of attributes of importance and trade-offs they would be willing to make between these characteristics. These assessments were followed by sociodemographic and medical practice-related questions.

Data were subsequently analyzed using a Dirichlet regression model, and marginal rates of substitution were calculated to quantify physicians’ willingness to accept treatment-related risks in exchange for benefits.

“Future studies should explore how these treatment attributes influence patients’ preferences,” Geiger and colleagues wrote in their conclusion.

Disclosures: Geiger disclosed full or part-time employment; receiving institutional sponsorship/funding from; and having personal stock/shares in Takeda.

Reference

  1. Geiger A, Michaels-Igbokwe C, Hernandez L, et al. Physicians’ preferences for later-line treatment of metastatic colorectal cancer in Germany and the UK. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 67P.

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