Medical Oncology (2018) 35:101
Phase II study of panitumumab combined with capecitabine
and oxaliplatin as ﬁrst-line treatment in metastatic colorectal cancer
patients: clinical results including extended tumor genotyping
· Vassiliki Kotoula
· Eleni Giannoulatou
· Georgia‑Angeliki Koliou
· Vasilios Karavasilis
· Andreas Koureas
· Mattheos Bobos
· Elpida Chalaralambous
· Emily Daskalaki
· George Tsironis
· Elisavet Pazarli
· Soa Chrisa
· Epaminontas Samantas
Ioannis G. Kaklamanos
· Ioannis Varthalitis
· Athina Konstantara
· Konstantinos N. Syrigos
· Dimitrios Pectasides
· George Fountzilas
Received: 14 May 2018 / Accepted: 27 May 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
This clinical trial assessed the eﬃcacy and toxicity of panitumumab combined with oxaliplatin and capecitabine as ﬁrst-line
treatment in KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. Patients with exon 2 KRAS wild-type
mCRC received panitumumab 9 mg/Kg, oxaliplatin 130 mg/m
, and capecitabine 2000 mg/m
repeated every 3 weeks.
The primary endpoint was objective response rate (ORR, minimum 42 responses). We retrospectively assessed mutations
in genes implicated in CRC with massively parallel sequencing; ERBB2 and EGFR ampliﬁcation with ﬂuorescence in situ
hybridization, and tumor-inﬁltrating lymphocyte density. Among 78 patients enrolled, 45 (57.7%) completed 6 cycles. Most
common grade 3–4 toxicities were skin rash (19.2%), diarrhea (18%), and neuropathy (6.4%). Among 5 (6.4%) potentially
treatment-related deaths, 2 (2.6%) were characterized toxic. Objective response occurred in 43 (55.1%) of the patients (com-
plete 6.4% and partial response 48.7%; stable 17.9% and progressive disease 7.7%), while 3.8% were non-evaluable and 15%
discontinued their treatment early. Additional mutations in KRAS/NRAS/BRAF were found in 11/62 assessable (18%) tumors.
After 51 months median follow-up, median progression-free (PFS) was 8.1 and overall survival 20.2 months, independently
of KRAS/NRAS/BRAF or PI3K-pathway mutation status. Patients with TP53 mutations (n = 34; 55%), as well as those with
left colon primary tumors (n = 66; 85%), had signiﬁcantly better PFS, also conﬁrmed in multivariate analysis. Although the
clinical trial met its primary endpoint, according to the current standards, the eﬃcacy and tolerability of the drug combination
are considered insuﬃcient. Extended genotyping yielded interesting results regarding the signiﬁcance of TP53 mutations.
ClinicalTrials.gov identiﬁer: NCT01215539, Registration date: Sep 29, 2010.
Keywords Metastatic colorectal cancer · Panitumumab · Tumor sidedness · TP53 · Next generation sequencing
Colorectal cancer (CRC) is the third most common malig-
nancy in the western world. A signiﬁcant proportion of
patients is diagnosed with metastatic (stage IV) disease,
while even patients with locoregional disease relapse after
surgical resection, independent of (neo)adjuvant treatment.
Systemic treatment for metastatic CRC (mCRC) has signiﬁ-
cantly evolved during the last two decades, with the incorpo-
ration of many novel antineoplastic agents which helped to
extend median life expectancy from approximately 9 months
in the era of ﬂuoropyrimidine monotherapy, to more than
24 months in recent years .
George Papaxoinis and Vassiliki Kotoula authors contributed
equally to this study.
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s1203 2-018-1160-1) contains
supplementary material, which is available to authorized users.
* George Papaxoinis
Extended author information available on the last page of the article