Abstract P5-20-10: Panitumumab, Gemcitabine and Carboplatin in Triple-Negative Metastatic Breast Cancer: Preliminary Results of a Phase II Trial of the Sarah Cannon Research Institute
Authors: Yardley DA , Ward P , Handricks C , Daniel B , Harwin W , Kannarkat G , Saez R , Shastry M , Chirwa T , Peacock N 
Published: August 2014

Abstract
Background: Triple-negative breast cancer (TNBC) is a poor prognosis subtype with treatment limited to chemotherapy. Over expression of epidermal growth factor receptor (EGFR) occurs in up to 70% of TNBC providing a potential targetable receptor for treatment. Panitumumab is an approved fully human, IgG2 monoclonal anti-EGFR antibody that inhibits intracellular growth signals dependent on receptor activation. The gemcitabine/platinum combination has demonstrated activity in metastatic as well as TNBC at various schedules and doses. We therefore investigated the efficacy and safety of panitumumab in combination with gemcitabine and carboplatin in patients (pts) with TNBC.
Methods: Eligibility criteria included: females with metastatic TNBC, 0–1 prior chemotherapy regimen for metastatic disease, ECOG PS 0–1, no brain metastases, no previous EGFR inhibitors and adequate organ function. All pts received gemcitabine 1500 mg/m2 IV, carboplatin AUC = 2.5 IV, and panitumumab 6 mg/kg IV every 2 weeks. A prophylactic skin regimen consisting of moisturizer, sunscreen and topical steroid was to be used 24 hours prior to study treatment and continued until panitumumab was discontinued. Pts were restaged after 3 treatment cycles and continued treatment until unacceptable toxicity or disease progression. If treatment benefit was demonstrated, and pts were experiencing toxicity or intolerance to gemcitabine, carboplatin or both, pts were allowed to discontinue either one or both agents and continue study treatment with panitumumab as a single agent or in combination. The primary endpoint of this study is progression free survival (PFS) with accrual of 70 pts necessary to detect an improvement in median PFS from 3.6 to 5.4 months (80% power, 10% level of significance).
Results: Between May 2010 and May 2012, 61 patients were enrolled with an accrual goal of 70 pts. This analysis is based on 47 pts. Pt characteristics include: median age 56, prior hormonal therapy 4%, no prior chemotherapy for metastatic disease in 87% (28% de novo stage IV), 1 prior chemotherapy for metastatic disease in 13%. Sites of metastatic disease included local regional/lymph nodes 70%, lung 57%, liver 32%, bone 26%, and others 23%. Best response to treatment was as follows: CR − 1 (2%), PR − 14 (30%), SD − 20 (43%), PD − 11 (23%), UE − 1 (2%). As 1st line TNBC therapy, the ORR was 34%. The most common grade 3/4 heme toxicities were neutropenia − 12 (25%), leucopenia − 7 (15%), anemia − 3 (6%) and thrombocytopenia − 2 (4%). Grade 3/4 non-hematologic toxicities were rash − 4 (9% with 1 grade 4), fatigue − 3 (6%) and DVT − 3 (6%). Grade 1 and 2 rash was present in 19 and 9 pts respectively. Archival tumor tissue was collected for correlative biomarker analysis to include PI3KCA, p53, PTEN, EGFR, and K-ras status.
Conclusions: The addition of panitumumab to gemcitabine and carboplatin in metastatic TNBC was active with an ORR of 32%. No new safety signals were identified and treatment was generally well tolerated with easily manageable toxicity. Full study results and correlative biomarker assessments will be reported.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-20-10.