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Cetuximab in Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Ovarian Cancer Without KRAS, NRAS, or BRAF
Julie G Fisher1, David Tait1, Elizabeth Garrett-Mayer2
1Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
Background:
The Targeted Agent and Profiling Utilization Registry (TAPUR) Study, a phase II basket study, evaluates anti-tumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known as drug targets.
Objective:
With no known genomic targets predictive of sensitivity to cetuximab, cetuximab was evaluated in patients with breast cancer (BC), non-small cell lung cancer (NSCLC), and ovarian cancer (OC), without KRAS, NRAS, or BRAF mutations.
Patients And Methods:
Eligible patients with advanced BC, NSCLC, and OC received a cetuximab loading dose, then weekly infusions (250 mg/m2 over 60 min). A Simon two-stage design, requiring ten patients in stage I, was employed per each disease-specific cohort. The primary endpoint was disease control (objective response or stable disease for at least 16 weeks). If two or more patients in stage I achieved disease control, the cohort would enroll 18 more patients in stage II. Power and alpha of the design are 85% and 10%, respectively. Secondary endpoints included progression-free survival, overall survival, and safety.
Results:
Patients with BC (n = 10), NSCLC (n = 10), and OC (n = 29) were enrolled between June 2016 and September 2018. No objective responses or stable disease for at least 16 weeks were observed in the BC and NSCLC cohorts. No objective responses and four patients with stable disease for at least 16 weeks were observed in the OC cohort. Six of 49 patients reported grade 3 or higher adverse events or serious adverse events at least possibly related to cetuximab.
Conclusions:
Cetuximab does not have clinical activity in patients with advanced BC, NSCLC, and OC without KRAS, NRAS, or BRAF mutations.
Clinical Trial Registration:
NCT02693535 (26 February, 2016).
Insights
Cetuximab showed no clinical activity in advanced breast, lung, or ovarian cancers lacking specific mutations. This targeted therapy was ineffective in patients without KRAS, NRAS, or BRAF alterations.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- The Targeted Agent and Profiling Utilization Registry (TAPUR) study investigates targeted agents in advanced cancers with known genomic alterations.
- This phase II basket study focuses on the anti-tumor activity of commercially available targeted agents.
Purpose of the Study:
- To evaluate the efficacy of cetuximab in patients with advanced breast cancer (BC), non-small cell lung cancer (NSCLC), and ovarian cancer (OC) lacking predictive genomic targets.
- Specifically, to assess cetuximab's activity in patients without KRAS, NRAS, or BRAF mutations.
Main Methods:
- A Simon two-stage design was used for BC, NSCLC, and OC cohorts, with primary endpoint of disease control (objective response or stable disease ≥16 weeks).
- Eligible patients received cetuximab loading dose followed by weekly infusions (250 mg/m²).
- Secondary endpoints included progression-free survival, overall survival, and safety.
Main Results:
- Enrollment included 10 patients with BC, 10 with NSCLC, and 29 with OC.
- No objective responses or sustained disease control were observed in BC or NSCLC cohorts.
- In the OC cohort, no objective responses were seen, but 4 patients achieved stable disease ≥16 weeks. Six patients experienced grade 3+ adverse events.
Conclusions:
- Cetuximab demonstrated no significant clinical activity in advanced BC, NSCLC, and OC patients without KRAS, NRAS, or BRAF mutations.
- These findings suggest cetuximab is not effective in these cancer types when these specific mutations are absent.
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