Effect of biopsy requirement on patient enrollment to phase I trials in cancer.

Abstract

3154 Background: The need for safer and more effective drugs for patients with cancer is a constant unmet need. Given their narrow therapeutic index, determination of dose and toxicity through phase I clinical trials is confined to patients with cancer. Recently, there has been a trend towards a greater demand for fresh tumor biopsies (Bx) from patients to better understand the pharmacodynamic and target effect of the drugs. We sought to determine whether the requirement for Bx among this vulnerable population had any detrimental effect. Methods: The study population included patients who enrolled to phase I trials between June 2022 (new EMR system) through January 2025 at a single NCI-designated comprehensive cancer center. All charts were reviewed and data collected included sex, race, age, diagnosis, and dates of consent, treatment start, last dose of study drug, off treatment, last contact/death; Bx site/approach/complications. Images were reviewed by an interventional radiologist to assess safety, with targets deemed appropriate biopsied under image guidance. For lung lesions or those < 1 cm, 20g core needle was used, while 18g core needle was used for others. Outcomes were analyzed by Mantel–Cox test using Prism GraphPad v 10. Results: 146 patients [male (n = 63, 43.2%), age 62, 23-82(median, range), NHW-81 (55.5%), NHB-23 (15.8%), Hispanic-24 (16.4%), and Asian-18 (12.3%)] consented to 25 clinical trials. Of these, 8 mandated paired tumor Bx, 15 were mandatory or optional Bx depending on cohort, and 2 did not require Bx. The most common diagnoses were colorectal (37, 25.3%), other GI (21, 14.4%), pancreas (18, 12.3%), lung (11, 7.5%), breast (6, 4.1%), prostate (3, 2.1%) and others (50, 34.2%). Bx samples were to be collected prior to the first dose of study drug (pre-dose) and repeated after the first 1-2 cycles (on-study). Image guidance included ultrasound (50, 57.5%), CT scans (34, 39.1%), and others (3, 3.4%). Overall, 62 patients (42.4%) provided 87 Bx samples; 25 paired Bx, 20 only pre-dose Bx, and 17 only on-study Bx. Five patients (3.4%) did not undergo Bx because it was deemed unsafe or high risk. The sites of Bx included liver (45, 51.7%), lung (9, 10.3%), lymph node (8, 9.2%), peritoneum (4, 4.6%), and others (21, 24.1%). Two patients experienced pneumothorax and recovered without sequelae. The median (mean) duration from consent to start of study treatment was 20 (20) days among Bx patients vs. 14 (16) among non Bx patients (p = 0.003). The median (mean) duration of time on study was 77 (91) days among Bx patients vs. 77 (125) among non Bx patients (p = 0.046). Conclusions: Over 40% of patients entering phase I trials underwent study specific Bx. The patients who underwent a Bx had a median delay of 6 days in receiving the first dose of study medication. Further in-depth review of medical records will help identify variables that may have led to shorter time on study for patients undergoing clinical trial related biopsies.