Cancer Chemother Pharmacol DOI 10.1007/s00280-014-2596-4
SHORT COMMUNICATION
Predicting success in regulatory approval from Phase I results Laeeq Malik · Alex Mejia · Helen Parsons · Benjamin Ehler · Devalingam Mahalingam · Andrew Brenner · John Sarantopoulos · Steven Weitman
Received: 30 July 2014 / Accepted: 15 September 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Drug development in oncology is resource intensive and has a high failure rate. In this exploratory analysis, we aimed to identify the characteristics and outcomes of published Phase I studies associated with future Food and Drug Administration (FDA) approval. Methods Phase I studies of approved and non-approved anticancer agents between 2000 and 2013 were retrospectively examined. Fisher’s exact and chi-squared tests were used to compare the potential predictive measures. Results Phase I studies of 88 anticancer agents (54 approved and 34 non-approved by the FDA), treating a total of 4,423 subjects, were examined. The median number of patients in Phase I trials of approved and non-approved agents was 44.5 and 32, respectively. A total of 423 subjects (86 reporting studies) had a complete responses, and 342 subjects (80 reporting studies) had a partial responses (PR). A higher number of PR (P 63 Number of patients with complete response (CR) (in quartiles) Number of reporting studies 0 1 2–5 >5 NA Percentage of patients with CR (in quartiles) Number of reporting studies 0 0–2.9 2.9–11.5 >11.5 NA Number of patients with partial response (PR) (in quartiles) Number of reporting studies ≤1 2 3–5 >5 NA Percentage of patients with partial response (PR) (in quartiles) Number of reporting studies ≤3.1 3.1–6.6 6.6–13.45 >13.45 NA Number of patients with stable disease (SD) (in quartiles) Number of reporting studies ≤7 8–12 13–20 >20 NA Percentage of patients with stable disease (SD) (in quartiles) Number of reporting studies ≤18.7 18.7–30 30–43
54 3,144
34 1,279
88 4,423
P value
0.053b 54 12 (22.22 %) 13 (24.07 %) 11 (20.37 %) 18 (33.33 %)
34 11 (32.35 %) 11 (32.35 %) 9 (26.47 %) 3 (8.82 %)
23 (26.14 %) 24 (27.27 %) 20 (22.73 %) 21 (23.86 %) 0.35b
52 32 (61.54 %) 10 (19.23 %) 3 (5.77 %) 7 (13.46 %) 2 (3.7 %)
34 26 (76.47 %) 3 (8.82 %) 3 (8.82 %) 2 (5.88 %) 0 (0 %)
86 58 (67.44 %) 13 (15.12 %) 6 (6.98 %) 9 (10.47 %) 2 (2.27 %) 0.049b
52 32 (61.54 %) 10 (19.23 %) 3 (5.77 %) 7 (13.46 %) 2 (3.7 %)
34 26 (76.47 %) 1 (2.94 %) 5 (14.71 %) 2 (5.88 %) 0 (0 %)
86 58 (67.44 %) 11 (12.79 %) 8 (9.3 %) 9 (10.47 %) 2 (2.27 %) 43 NA Duration of complete response (CR), in weeks (in quartiles) Number of reporting studies ≤27 27–48 48–80 >80 NA Duration of partial response (PR), in weeks (in quartiles) Number of reporting studies ≤18 18–24 24–41 >41 NA Number of patients with a partial response
SHORT COMMUNICATION
Predicting success in regulatory approval from Phase I results Laeeq Malik · Alex Mejia · Helen Parsons · Benjamin Ehler · Devalingam Mahalingam · Andrew Brenner · John Sarantopoulos · Steven Weitman
Received: 30 July 2014 / Accepted: 15 September 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Drug development in oncology is resource intensive and has a high failure rate. In this exploratory analysis, we aimed to identify the characteristics and outcomes of published Phase I studies associated with future Food and Drug Administration (FDA) approval. Methods Phase I studies of approved and non-approved anticancer agents between 2000 and 2013 were retrospectively examined. Fisher’s exact and chi-squared tests were used to compare the potential predictive measures. Results Phase I studies of 88 anticancer agents (54 approved and 34 non-approved by the FDA), treating a total of 4,423 subjects, were examined. The median number of patients in Phase I trials of approved and non-approved agents was 44.5 and 32, respectively. A total of 423 subjects (86 reporting studies) had a complete responses, and 342 subjects (80 reporting studies) had a partial responses (PR). A higher number of PR (P 63 Number of patients with complete response (CR) (in quartiles) Number of reporting studies 0 1 2–5 >5 NA Percentage of patients with CR (in quartiles) Number of reporting studies 0 0–2.9 2.9–11.5 >11.5 NA Number of patients with partial response (PR) (in quartiles) Number of reporting studies ≤1 2 3–5 >5 NA Percentage of patients with partial response (PR) (in quartiles) Number of reporting studies ≤3.1 3.1–6.6 6.6–13.45 >13.45 NA Number of patients with stable disease (SD) (in quartiles) Number of reporting studies ≤7 8–12 13–20 >20 NA Percentage of patients with stable disease (SD) (in quartiles) Number of reporting studies ≤18.7 18.7–30 30–43
54 3,144
34 1,279
88 4,423
P value
0.053b 54 12 (22.22 %) 13 (24.07 %) 11 (20.37 %) 18 (33.33 %)
34 11 (32.35 %) 11 (32.35 %) 9 (26.47 %) 3 (8.82 %)
23 (26.14 %) 24 (27.27 %) 20 (22.73 %) 21 (23.86 %) 0.35b
52 32 (61.54 %) 10 (19.23 %) 3 (5.77 %) 7 (13.46 %) 2 (3.7 %)
34 26 (76.47 %) 3 (8.82 %) 3 (8.82 %) 2 (5.88 %) 0 (0 %)
86 58 (67.44 %) 13 (15.12 %) 6 (6.98 %) 9 (10.47 %) 2 (2.27 %) 0.049b
52 32 (61.54 %) 10 (19.23 %) 3 (5.77 %) 7 (13.46 %) 2 (3.7 %)
34 26 (76.47 %) 1 (2.94 %) 5 (14.71 %) 2 (5.88 %) 0 (0 %)
86 58 (67.44 %) 11 (12.79 %) 8 (9.3 %) 9 (10.47 %) 2 (2.27 %) 43 NA Duration of complete response (CR), in weeks (in quartiles) Number of reporting studies ≤27 27–48 48–80 >80 NA Duration of partial response (PR), in weeks (in quartiles) Number of reporting studies ≤18 18–24 24–41 >41 NA Number of patients with a partial response
