Trends in Grade 5 Toxicity and Response in Phase I Trials in Hematologic Malignancy: 20-Year Experience From the Cancer Therapy Evaluation Program at the National Cancer Institute

• DOI: 10.1200/jco.21.02190
• Publication Date: 2022-03-09T20:59:17Z
• Authors: Dai Chihara; Erich P. Huang; Shanda R. Finnigan; Lisa M. Cordes; Nebojsa Skorupan; Yoko Fukuda; Larry V. Rubinstein; S. Percy Ivy; James H. Doroshow; Loretta J. Nastoupil; Christopher R. Fl...; Naoko Takebe
• Keywords: Leukemia, Myeloid, Acute; 03 medical and health sciences; 0302 clinical medicine; Hematologic Neoplasms; Humans; Antineoplastic Agents; Leukemia, Lymphocytic, Chronic, B-Cell; National Cancer Institute (U.S.); United States; 3. Good health

PURPOSE Cancer drug development has largely shifted from cytotoxic chemotherapy to targeted treatment in the past two decades. Although previous studies have highlighted improvement response rates recent phase I trials, disease-focused reporting is limited. METHODS We integrated patient-level data for patients with hematologic malignancies who participated trials sponsored by National Institute Therapy Evaluation Program between January 2000 and May 2019 estimated trend of grade 5 toxicity disease subtype over time. RESULTS analyzed 161 involving 3,308 patients, all whom were assessed 2,404 evaluable therapy. The overall rate toxicities was 1.81% (95% CI, 1.36 2.27), no significant change Baseline characteristics associated higher risk age performance status ≥ 2 at enrollment. Overall (ORR) complete (CR) during study period 25.1% 14.7%, respectively. A increase both ORR CR observed time (ORR, 18.5% 2000-2005, 25.9% 2006-2012, 50.6% 2013-2019, P < .001). varied across subtypes: 20.2% acute myeloid leukemia, 9.1% myelodysplastic syndrome, 43.2% lymphoma, 42.9% chronic lymphocytic 15.1% lymphoblastic 16.5% myeloma. CONCLUSION Over time, malignancy improved meaningfully, whereas toxicity-related death remains stable. This provides broad experience that physicians can use when discussing potential outcomes considering participation trials.