Positive findings from three Targeted Agent and Profiling Utilization Registry (TAPUR) study cohorts on the potential benefit of molecularly targeted drugs in patients with advanced colorectal cancer were presented at the 2020 Gastrointestinal Cancers Symposium.1-3
The TAPUR study is the first clinical trial conducted by ASCO. It aims to describe the performance (both safety and efficacy) of U.S. Food and Drug Administration–approved, targeted anticancer drugs prescribed for the treatment of patients with advanced cancer that has a potentially actionable genomic alteration.
Cobimetinib Plus Vemurafenib in Patients With BRAF V600E–Mutant Disease
In a cohort of heavily pretreated patients with BRAF V600E–mutated colorectal cancer, the combination of the MEK inhibitor cobimetinib and the BRAF inhibitor vemurafenib showed antitumor activity. Results were reported by Klute et al.1
Sixty-three percent of patients in the cohort had had three or more prior systemic regimens. Patients had a BRAF V600E/D/K/R mutation and no MAP2K1/2, MEK1/2, or NRAS mutations. The recommended dosing was 60 mg of cobimetinib orally once daily for 21 days, 7 days off, and 960 mg of vemurafenib orally twice daily.
In the 28 patients eligible for evaluation, eight partial responses were reported, and eight patients had stable disease lasting 16 weeks or longer. Disease control and objective response rates were 57% and 29%, respectively. Twelve patients had at least one grade 3 adverse event or serious adverse event possibly related to the combination.
Pertuzumab Plus Trastuzumab in ERBB2-Amplified Colorectal Cancer
In another cohort of patients with heavily pretreated colorectal cancer—these, with an ERBB2 amplification—treatment with the anti-HER2 monoclonal antibodies pertuzumab and trastuzumab elicited responses. These findings were published by Gupta et al.2
All 28 patients in the cohort had an ERBB2 amplification, but one also had an ERBB2 mutation. Seventy-nine percent of patients had undergone three or more prior treatments. After initial dosing, the dosing regimen recommended was 420 mg of intravenous pertuzumab over 30 to 60 minutes every 3 weeks, plus 6 mg/kg of intravenous trastuzumab over 30 to 60 minutes every 3 weeks.
Four partial responses were seen, as well as 10 patients with stable disease of 16 weeks or more. The reported disease control rate was 50% (90% confidence interval [CI] = 36%–60%), and the objective response rate was 14% (95% CI = 4%–33%). Two patients had at least one grade 3 adverse event or serious adverse event classified as possibly related to pertuzumab/trastuzumab, including anemia, infusion reaction, and left-ventricular dysfunction.
Pembrolizumab in Patients With High Tumor Mutational Burden
In a cohort of previously treated patients with colorectal cancer and a high tumor mutational burden, pembrolizumab showed activity. This data was reported by Meiri et al.3
Patients had high tumor mutational burden—defined as nine or more mutations per megabase—by either a FoundationOne test or other test approved by the molecular tumor board. Tumor burden ranged from 9 to 54 mutations/megabase. Patients with microsatellite instability–high tumors were ineligible for inclusion. Patients were given either 2 mg/kg of pembrolizumab (n = 8) or 200 mg (n = 20) intravenously over 30 minutes every 3 weeks.
Of the 27 patients included in the analysis, tumor microsatellite status was reported stable in 25 patients, ambiguous in 1, and not available for 1. One partial response in a patient with a microsatellite-stable status and 10 mutations/megabase was recorded. Seven patients had stable disease for 16 weeks or longer. The disease control rate was 28%, and the objective response rate was 4%.
Two patients had grade 3 adverse events possibly related to pembrolizumab, including abdominal infection, anorexia, colitis, diarrhea, fatigue, nausea, and vomiting. One patient had a serious adverse event—acute kidney injury.
DISCLOSURE: For full disclosures of all study authors, visit meetinglibrary.asco.org.
1. Klute K, Garrett-Mayer E, Halabi S, et al: Cobimetinib plus vemurafenib in patients with colorectal cancer with BRAF V600E mutations. 2020 Gastrointestinal Cancers Symposium. Abstract 122. Presented January 25, 2020.
2. Gupta R, Garrett-Mayer E, Halabi S, et al: Pertuzumab plus trastuzumab in patients with colorectal cancer with ERBB2 amplification or overexpression. 2020 Gastrointestinal Cancers Symposium. Abstract 132. Presented January 25, 2020.
3. Meiri E, Garrett-Mayer E, Halabi S, et al: Pembrolizumab in patients with colorectal cancer with high tumor mutational burden. 2020 Gastrointestinal Cancers Symposium. Abstract 133. Presented January 25, 2020.