| General information |
| Database: | DB00258 |
| Objective: | Acquired resistance to antiepidermal growth factor receptor (antiEGFR) therapy may be caused by EGFRverbb2 avian erythroblastic leukemia viral oncogene homolog 2 (ErbB2) heterodimerization and pathway reactivation. In preclinical studies, inhibiting ErbB2 blocked this resistance mechanism and resensitized cells to antiEGFR therapy. Cetuximab targets EGFR, whereas lapatinib inhibits both EGFR and ErbB2. The objective of thisphase 1 trial was to assess the safety, doselimiting toxicities (DLTs), and maximum tolerated doses (MTDs) of cetuximab and lapatinib in patients with solid tumors. |
| Authors: | Deeken JF, et al |
| Title: | a phase 1 study of cetuximab and lapatinib in patients with advanced solid tumor malignancies. |
| Journal: | Cancer. |
| Year: | 2015 |
| PMID: | 25641763 |
| Trial Design |
| Clinical Trial Id: | NCT01184482 |
| Agent: | cetuximab and lapatinib
|
| Target: | NA
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | cetuximab +lapatinib |
| Study Type: | a singleinstitution, openlabel, doseescalation, sequential cohort, phase I clinical study |
| Key Patients Feature: | Adult patients who had refractory solid tumors that were treatable with cetuximab at the time of the study (Kras wildtype colorectal, nonsmall cell lung, head and neck, and anal squamous cell cancers) were enrolled;Fiftynine percent of patients had received prior antiEGFR therapy. |
| Biomarker: | Decreased expression of EGFR/ErbB2 pathway components;expression in the PI3K, Jak/Stat, and MAPK pathways |
| Biomark Analysis: | Decreased expression of EGFR/ErbB2 pathway components after treatment was correlated with response, whereas increased expression in the PI3K, Jak/Stat, and MAPK pathways occurred in nonresponders. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received standard weekly cetuximab with escalating lapatinib doses of 750 mg, 1000 mg, or 1250 mg daily in 3week cycles. DLTs were monitored through the end of cycle 2. Pretreatment and posttreatment tumor biopsies and germline DNA samples were obtained for correlative studies. |
| Primary End Point: | the maximum tolerated dose (MTD) of the combination of lapatinib and cetuximab. |
| Secondary End Point: | clinical activity as well as the translational studies. |
| Patients Number: | 22 |
| Trial Results |
| DLT_MTD: | No patient experienced a DLT at the highest dose level, and no grade 4 toxicity was observed. |
| Objective Response Rate: | Response included no complete responses, 3 partial responses, 9 patients with stable disease, and 6 patients with disease progression, for an overall response rate of 17% |
| Disease Control Rate: | a clinical benefit rate of 67%;the clinical benefit rate in patients who had previously received antiEGFR therapy was 70%. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common toxicities included rash and diarrhea. |
| Conclusions: | The combination of cetuximab and lapatinib was well tolerated, had the expected toxicities, and exhibited notable clinical activity, including in patients who had received previous antiEGFR therapy. Further clinical study of this combination is warranted. |