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