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Olaparib in Patients With Solid Tumors With ATM Alterations: Results From the Targeted Agent and Profiling
Daniel R Carrizosa1, Michael Rothe2, Pam K Mangat2
1Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC.
Purpose:
The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of four cohorts of patients with ATM-altered tumors treated with olaparib are reported: colorectal cancer (CRC), lung cancer (LC), pancreatic cancer (PC), and other solid tumors (histology-pooled, HP).
Methods:
Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were OR, progression-free survival, overall survival, duration of response or SD, and safety.
Results:
Patients with CRC (n = 30), LC (n = 20), PC (n = 28), or other advanced cancers (n = 38) with ATM alterations were enrolled. The DC rates were 23% (one-sided 90% CI, 8 to 100; P = .38), 45% (one-sided 90% CI, 32 to 100; P = .0004), 28% (one-sided 90% CI, 14 to 100; P = .14), and 25% (one-sided 90% CI, 16 to 100), respectively. The null hypothesized 15% DC rate was rejected for the LC and HP cohorts but not the CRC and PC cohorts. Twenty of 116 patients (17%) experienced treatment-related grade 3 adverse events (AE) or serious AEs.
Conclusion:
Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.
Insights
Olaparib showed antitumor activity in patients with ATM-altered lung cancer and other solid tumors. However, it did not meet efficacy criteria for colorectal or pancreatic cancer patients in this phase II trial.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- The Targeted Agent and Profiling Utilization Registry Study (TAPUR) is a phase II basket trial.
- This study evaluates the efficacy of targeted agents in patients with advanced cancer and specific genomic alterations.
Purpose of the Study:
- To assess the antitumor activity of olaparib in patients with ATM-altered colorectal cancer (CRC), lung cancer (LC), pancreatic cancer (PC), and other solid tumors (histology-pooled, HP).
Main Methods:
- Patients with advanced solid tumors and ATM alterations were enrolled.
- The primary endpoint was disease control (DC) rate, defined as objective response (OR) or stable disease (SD) for at least 16 weeks.
- Statistical analysis used Simon's two-stage design for histology-specific cohorts and a one-sided 90% CI for the HP cohort.
Main Results:
- Disease control (DC) rates were 23% for CRC, 45% for LC, 28% for PC, and 25% for HP.
- The null hypothesis of a 15% DC rate was rejected for the LC and HP cohorts.
- 17% of patients experienced grade 3 or serious adverse events.
Conclusions:
- Olaparib demonstrated a signal of activity in patients with ATM-altered lung cancer and other solid tumors.
- Olaparib did not meet the prespecified criteria for efficacy in ATM-altered colorectal and pancreatic cancer cohorts.
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