Panitumumab In Metastatic Colorectal Cancer Research Articles

Unveiling acquired resistance to anti-EGFR therapies in colorectal cancer: a long and winding road.

Emergence of acquired resistance limits the efficacy of the anti-EGFR therapies cetuximab and panitumumab in metastatic colorectal cancer. In the last decade, preclinical and clinical cohort studies have uncovered genomic alterations that confer a selective advantage to tumor cells under EGFR blockade, mainly downstream re-activation of RAS-MEK signaling and mutations in the extracellular domain of EGFR (EGFR-ECD). Liquid biopsies (genotyping of ctDNA) have been established as an excellent tool to easily monitor the dynamics of genomic alterations resistance in the blood of patients and to select patients for rechallenge with anti-EGFR therapies. Accordingly, several clinical trials have shown clinical benefit of rechallenge with anti-EGFR therapy in genomically-selected patients using ctDNA. However, alternative mechanisms underpinning resistance beyond genomics -mainly related to the tumor microenvironment-have been unveiled, specifically relevant in patients receiving chemotherapy-based multi-drug treatment in first line. This review explores the complexity of the multifaceted mechanisms that mediate secondary resistance to anti-EGFR therapies and potential therapeutic strategies to circumvent acquired resistance.

Circulating tumor DNA to guide rechallenge with panitumumab in metastatic colorectal cancer: the phase 2 CHRONOS trial

Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC), but the emergence of resistance mutations restricts their efficacy. We previously showed that RAS, BRAF and EGFR mutant alleles, which appear in circulating tumor DNA (ctDNA) during EGFR blockade, decline upon therapy withdrawal. We hypothesized that monitoring resistance mutations in blood could rationally guide subsequent therapy with anti-EGFR antibodies. We report here the results of CHRONOS, an open-label, single-arm phase 2 clinical trial exploiting blood-based identification of RAS/BRAF/EGFR mutations levels to tailor a chemotherapy-free anti-EGFR rechallenge with panitumumab (ClinicalTrials.gov: NCT03227926; EudraCT 2016-002597-12). The primary endpoint was objective response rate. Secondary endpoints were progression-free survival, overall survival, safety and tolerability of this strategy. In CHRONOS, patients with tissue-RAS WT tumors after a previous treatment with anti-EGFR-based regimens underwent an interventional ctDNA-based screening. Of 52 patients, 16 (31%) carried at least one mutation conferring resistance to anti-EGFR therapy and were excluded. The primary endpoint of the trial was met; and, of 27 enrolled patients, eight (30%) achieved partial response and 17 (63%) disease control, including two unconfirmed responses. These clinical results favorably compare with standard third-line treatments and show that interventional liquid biopsies can be effectively and safely exploited in a timely manner to guide anti-EGFR rechallenge therapy with panitumumab in patients with mCRC. Further larger and randomized trials are warranted to formally compare panitumumab rechallenge with standard-of-care therapies in this patient setting.

The Role of Pre-treatment Inflammatory Biomarkers in the Prediction of an Early Response to Panitumumab in Metastatic Colorectal Cancer.

BackgroundSystemic inflammation is a critical component of the development and progression of several types of cancer. Neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) are simple, inexpensive, and reliable predictors of the systemic inflammatory response to the therapy in different malignant tumors, including colorectal cancer.MethodsMetastatic colorectal cancer (mCRC) patients treated with panitumumab plus chemotherapy at first-line at the medical oncology unit of Fondazione Institute for Research, Hospitalization and Health Care (IRCCS) Policlinico San Matteo di Pavia between January 1st 2016 and February 1st 2021 were retrospectively analyzed. NLR and LMR were divided into two groups (high and low) based on the cut-off points, with the estimation of the prognostic accuracy of NLR for the early treatment response as the primary end-point of this study.ResultsThe receiver operating characteristic (ROC) analysis showed a fair prognostic accuracy of NLR for early treatment response (area under the curve (AUC)=0.76, 95% CI: 0.62-0.89). A slightly lower prognostic accuracy was found for LMR (AUC=0.71, 95% CI: 0.57-0.85). In the univariable proportional hazard Cox model, no effect of NLR on PFS was found (NLRHigh vs. NLRLow HR=1.3; 95% CI: 0.7-2.4, p=0.414). Patients with higher levels of LMR showed a trend towards higher PFS (LMRHigh vs. LMRLow HR=0.4; 95% CI: 0.2-1.1, p=0.066). No association was found between NLR (or LMR) and skin toxicity.ConclusionsNLR and LMR may be used as biomarkers of prognostic accuracy for the early treatment response in mCRC patients treated with panitumumab.

Investigating racial differences in treatment responses through analysis of real-world data (RWD).

e18141 Background: Clinical trials remain the most reliable means to evaluate drug efficacy and safety for evidence-based cancer care. However, there is a significant racial disparity among participants in clinical trials. For example, only 1-3% of the participants in registration trials of immune checkpoint inhibitors (CPIs) in advanced non-small cell lung cancers (aNSCLCs) were Black. RWD data enable assessment of whether clinical trial results can be generalized to broader populations. Methods: We analyzed clinical records of > 145,000 cancer patients treated at Mount Sinai hospitals. Therapeutic agents approved by FDA in recent years were assessed for responses across various race groups. Time to treatment discontinuation (TTD) was used as a surrogate clinical endpoint for outcomes. Results: Overall we did not observe significant differences in TTD among different race groups for the following drugs and indications we examined: palbociclib in metastatic breast cancer (mBC), EGFR tyrosine kinase inhibitors in aNSCLC, EGFR antibody cetuximab and panitumumab in metastatic colorectal cancer with wild type KRAS, abiraterone in metastatic castration-resistant prostate cancer (mCRPC), enzalutamide in mCRPC, sorafenib in unresectable hepatocellular carcinoma (HCC), CPIs in metastatic melanoma. For example, the median TTD of palbociclib in combination with fulvestrant or letrozole in post-menopausal women with HR+HER2- mBC was 181, 261, and 160 days in White (n = 114), Black (n = 55), other (n = 48) race groups, respectively (P = 0.61, log-rank test). Among patients with unresectable HCC treated with sorafenib, the median TTD was 64, 49, and 67 days in the White (n = 201), Black (n = 127) and other (n = 243) race groups, respectively (P = 0.70). However, when CPIs in aNSCLC were examined, we observed a significantly longer TTD in the Black group (median TTD not reached; n = 77) compare to the non-Black group (169 days, 95% CI 133-331; n = 211), P = 0.0049, median follow up 194 days. Conclusions: RWD showed there are no apparent differences of treatment response in various race groups for most new therapeutic agents. Preliminary results of CPIs in aNSCLC suggested a favorable response in the Black than the non-Black population.

Relationships between tumour response and primary tumour location, and predictors of long-term survival, in patients with RAS wild-type metastatic colorectal cancer receiving first-line panitumumab therapy: retrospective analyses of the PRIME and PEAK clinical trials

BackgroundData from two trials of panitumumab in metastatic colorectal cancer (mCRC) were retrospectively analysed to investigate the effects of primary tumour location on early-tumour shrinkage (ETS) and depth of response (DpR), and identify factors predicting long-term survival.MethodsPatients with RAS wild-type mCRC from PRIME (NCT00364013) and PEAK (NCT00819780) were included. ETS was defined as a ≥30% reduction in the sum-of-the-longest-diameters of measurable target lesions at eight weeks. DpR was the maximum percentage change from baseline to nadir in patients with shrinkage. Univariate and multivariate logistic analyses of short- versus long-term survivor data were performed.ResultsA total of 435/559 (78%) patients had left-sided disease. Of these, a higher proportion of patients treated with panitumumab versus comparator achieved ETS (PRIME: 62% vs. 36%; PEAK: 58% vs. 41%); median DpR was also higher with panitumumab (PRIME: 59% vs. 49%; PEAK: 70% vs. 48%). In pooled analyses of the studies, more patients with right-sided disease achieved ETS if treated with panitumumab than comparator (39% vs. 29%). Panitumumab treatment consistently predicted long-term survival.ConclusionsFirst-line panitumumab was associated with improved ETS and DpR vs. comparator in patients with left-sided mCRC. ETS may identify a subgroup of patients with right-sided disease who might respond to panitumumab.

P-319 - Characteristics and response outcomes of long-term survivors in studies of first-line panitumumab for metastatic colorectal cancer

P-319 - Characteristics and response outcomes of long-term survivors in studies of first-line panitumumab for metastatic colorectal cancer

Panitumumab in Metastatic Colorectal Cancer: The Importance of Tumour RAS Status.

Tumour biomarker status is being used more and more frequently to guide treatment decisions in patients with metastatic colorectal cancer (mCRC). Continued cycles of hypothesis generation and biomarker testing in retrospective, prospective–retrospective and prospective analyses from studies of the epidermal growth factor (EGFR)-targeted monoclonal antibodies (mAbs), panitumumab and cetuximab, have resulted in improved patient selection in mCRC. Initial data suggested EGFR-targeted mAb treatment should be limited to patients with KRAS exon 2 wild-type (WT) tumours, but the availability of tumour samples from large phase III studies permitted evaluation of additional potential biomarkers of activity for these agents. Subsequent analyses further refined the target population to those patients whose tumours were WT for KRAS and NRAS exons 2, 3 and 4 (i.e., those with RAS WT status). Here, we review key clinical data for panitumumab in mCRC across the lines of treatment, assessing in detail the impact of more comprehensive RAS selection on patient outcomes. Panitumumab data across first- to third-line therapy consistently demonstrate that by testing tumour RAS status, it is possible to select patients more likely to benefit from treatment.

COLD-PCR protocols to enrich KRAS codon 61 and 146 mutations in heterogeneous tumor samples.

e22125 Background: About 40% of colorectal cancer patients show mutations on codon 12-13 of KRAS but other, less frequent and mutually exclusive mutations, were described. In Italy, treatments with Cetuximab or Panitumumab for metastatic colorectal cancer are granted only for patients with no mutations on RAS genes and analysis of codon 12,13,59,61,117,146 of KRAS and NRAS are requested before the treatment scheduling. Principal limitation of conventional PCR-based methods for mutation analysis is the inability to selectively amplify low percentages of somatic variants in an elevated background of wild-type sequences. CO-amplification at Lower Denaturation temperature PCR (COLD-PCR) is a simple approach of PCR that selectively enriches minority alleles in a mixture of wild-type and mutant sequences. This method requires the definition of a Critical Temperature (Tc) for each Dna sequence, lower than the melting temperature, at which mismatched Dna heteroduplex (WT-mutated alleles) are preferentially denatured, promoting selective amplification of mutant sequences. Minor allele enrichment by COLD-PCR can be performed in association to different methods of variants detection: Sanger Sequencing, HRM analysis, Pyrosequencing Methods: Comparison of theoretical sensitivity achievable after PCR or COLD-PCR amplification was carried out analyzing serial dilution of mutated cell lines DNA into WT DNA (from 50% to 0.25%). To optimize the enrichment of minority alleles we developed a Full COLD-PCR protocol to analyze the Tm-increasing mutation (183 A>C) on KRAS codon 61 and a Fast COLD-PCR protocol to analyze the Tm-reducing mutation (436 G>A) on KRAS codon 146. Critical temperature was defined experimentally. Results: In KRAS codon 61 and 146 analysis, minimum detectable percentage of mutated allele in WT background was about 10% using conventional PCR followed by both Sanger sequencing and HRM. Conversely limit of sensitivity reached 0.5% using both detection methods after COLD-PCR Conclusions: Our experiments proved as COLD-PCR could be a rapid and economic approach, adaptable to investigate other somatic variants, to enrich very low percentages of mutant alleles in very heterogeneous tumor samples.

Panitumumab safety for treating colorectal cancer

Introduction: Panitumumab is a human IgG2 mAb against the EGFR, inhibiting tumor cell proliferation, survival and angiogenesis. It has demonstrated clinical efficacy in metastatic colorectal cancer (CRC) in combination with chemotherapy in first- and second-line settings and as monotherapy in third-line setting. Recently, mutations in the RAS genes have been shown to be predictive of lack of efficacy, panitumumab should be restricted to patients with RAS wild-type (wt) tumors.Areas covered: This review focuses on main efficacy results of panitumumab in metastatic CRC in first-, second- and third-line settings in combination with chemotherapy or as monotherapy. Additionally, we have covered safety aspects of this agent in these indications, especially in K-RAS and all RAS wt patients. These safety aspects refer to the most common toxicities (i.e., acne-like skin rash, diarrhea and hypomagnesaemia).Expert opinion: Panitumumab adds to the armamentarium of effective agents in the treatment of metastatic CRC. Due to its human origin, panitumumab is a well-tolerated agent with low rates of infusional reactions. Skin toxicity is frequent and should be pre-emptively treated. Other common toxicities related to panitumumab treatment, such as diarrhea and hypomagnesaemia, should be closely monitored to ensure early treatment or substitution.

MiR-181a is associated with poor clinical outcome in patients with colorectal cancer treated with EGFR inhibitor

AimsmiR-181a expression is frequently altered in different types of cancer. Members of the Wnt/β-catenin signalling pathway, which is commonly altered in colorectal cancer (CRC), have been reported as molecular interaction...

Panitumumab in metastatic colorectal cancer

Increasing chemotherapeutic and targeted drug options has led to improved overall survival in metastatic colorectal cancer. Panitumumab is a fully humanized monoclonal antibody that binds to the EGF receptor and inhibits downstream cell signaling with net effects of inhibition of tumor growth, induction of apoptosis and inhibition of angiogenesis. Panitumumab leads to improved response rate and progression-free survival when used in combination with chemotherapy and as monotherapy in metastatic colorectal cancer. This benefit is limited to patients who have non-mutated KRAS tumors, and regulatory agencies worldwide have restricted panitumumab to this patient population. Rash is a common side effect of panitumumab, and prophylactic skin treatments are advised. The optimal use of panitumumab is evolving and will become further defined with results of upcoming clinical trials and improved identification of biomarkers predicting benefit of this class of drugs

A Novel Fully Automated Molecular Diagnostic System (AMDS) for Colorectal Cancer Mutation Detection

Background KRAS, BRAF and PIK3CA mutations are frequently observed in colorectal cancer (CRC). In particular, KRAS mutations are strong predictors for clinical outcomes of EGFR-targeted treatments such as cetuximab and panitumumab in metastatic colorectal cancer (mCRC). For mutation analysis, the current methods are time-consuming, and not readily available to all oncologists and pathologists. We have developed a novel, simple, sensitive and fully automated molecular diagnostic system (AMDS) for point of care testing (POCT). Here we report the results of a comparison study between AMDS and direct sequencing (DS) in the detection of KRAS, BRAF and PI3KCA somatic mutations.Methodology/Principal FindingDNA was extracted from a slice of either frozen (n = 89) or formalin-fixed and paraffin-embedded (FFPE) CRC tissue (n = 70), and then used for mutation analysis by AMDS and DS. All mutations (n = 41 among frozen and 27 among FFPE samples) detected by DS were also successfully (100%) detected by the AMDS. However, 8 frozen and 6 FFPE samples detected as wild-type in the DS analysis were shown as mutants in the AMDS analysis. By cloning-sequencing assays, these discordant samples were confirmed as true mutants. One sample had simultaneous “hot spot” mutations of KRAS and PIK3CA, and cloning assay comfirmed that E542K and E545K were not on the same allele. Genotyping call rates for DS were 100.0% (89/89) and 74.3% (52/70) in frozen and FFPE samples, respectively, for the first attempt; whereas that of AMDS was 100.0% for both sample sets. For automated DNA extraction and mutation detection by AMDS, frozen tissues (n = 41) were successfully detected all mutations within 70 minutes.Conclusions/SignificanceAMDS has superior sensitivity and accuracy over DS, and is much easier to execute than conventional labor intensive manual mutation analysis. AMDS has great potential for POCT equipment for mutation analysis.

Pre-emptive skin toxicity treatment for anti-EGFR drugs: evaluation of efficacy of skin moisturizers and lymecycline. A phase II study

Anti-epidermal growth factor receptor (EGFR) target therapies like erlotinib for metastatic lung cancer and cetuximab or panitumumab for metastatic colorectal cancer (mCRC) cause skin reaction that seems to be related to treatment efficacy. Skin toxicity evaluation protocol with panitumumab study has shown that preemptive treatment reduces the incidence of ≥Grade 2 (G2) skin toxicity in mCRC treated with panitumumab. Aim of this study is to evaluate if preemptive skin toxicity treatment with different drugs has good efficacy in patients receiving anti-EGFR therapies, such as cetuximab, panitumumab, and erlotinib, for mCRC and metastatic lung cancer. Treatment included skin moisturizers with sunscreen and lymecycline 300 mg/daily. Primary objective is to reduce the incidence of ≥G2 skin toxicity during the first 3 months of therapy. Toxicities are reported with confidence interval at 95%. Quality of life was assessed with Dermatology Life Quality Index every 2 weeks and evaluated with repeated measure ANOVA. Fifty-one patients with mCRC (60.8%) and metastatic lung cancer (39.2%) were enrolled. Anticancer drugs were erlotinib/cetuximab/panitumumab 20:30:1. At 3-month evaluation, 27.4% patients had =G2 skin toxicity. Skin toxicity was not related with age (p = 0.67), sex (p = 0.65), previous chemotherapy regimens (p = 0.41), and current anti-EGFR treatment (p = 0.22). No gastrointestinal or hematological toxicities related to lymecycline were observed. Only six patients required further drugs. Quality of life analysis did not show a significant difference from the beginning and the end of treatment. Data show efficacy of preemptive treatment with a well-tolerated profile. A reduction of severe skin toxicities is shown with an increase of grade 1 toxicities, not leading to anti-EGFR dose reduction and with better quality of life for patients.

Is Codon 13 KRAS Mutation Biologically Different from Codon 12 Mutation?

The introduction into clinical practice of KRAS mutational status for selection of patients has dramatically improved the results from use of anti-EGFR monoclonal antibodies cetuximab or panitumumab for metastatic colorectal cancer. More refined selection of patients by means of other molecular alterations, for example BRAF, PIK3CA, and NRAS has enabled further increases in responses to first-line and other therapy for metastatic disease. Elucidation of differences among specific subtypes of KRAS mutations affecting sensitivity, and identification of other mechanisms by which tumor cell resistance is acquired, revealing “druggable” molecular targets to overcome resistance, are clearly a priority of clinical research. Recent data have revealed potentially different activity of the G13D KRAS mutation in conferring resistance to cetuximab. This review examines the most recent evidence available on codon 13 mutation in metastatic colorectal cancer, including both preclinical and available clinical data, indicating differences between codon 13 and other KRAS mutations and analyzing its prognostic and predictive use in EGFR-targeted therapy.

A Single Institutional Experience with Panitumumab in Metastatic Colorectal Cancer

Introduction: Panitumumab is an EGFR inhibitor approved for use in metastatic refractory colorectal cancer. It is unclear whether patients who have progressed on cetuximab may benefit from subsequent panitumumab therapy. This retrospective analysis was conducted to describe the experience at The Ohio State University with panitumumab including in patients who have progressed on cetuximab. Methods: Patients who received at least 1 dose of panitumumab between September 2006 and December 2011 were identified using the hospital’s pharmacy database. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 was used to assess responses and Kaplan-Meier curves were used to estimate progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients (median age 61 years) were identified. Sixty-seven percent of patients had tumors with wild-type KRAS, 3.4% had tumors with mutated KRAS and the KRAS status was unknown in 29.9%. Twenty-four percent of the patients had an ECOG performance status of 2 or above and 59.8% of patients had received ≥ 2 prior lines of chemotherapy. Thirty-two percent of patients received single-agent panitumumab while 68% received it in combination with chemotherapy. Of the patients with KRAS wild-type tumors, 10 (17.2%) had objective responses (3 complete, 7 partial) and 26 (44.8%) had stable disease. Median PFS and OS were 5.0 and 9.0 months. The presence of a rash, improved ECOG performance status and coadministration with either irinotecan or FOLFIRI, led to a significantly better OS in univariate analysis. Among patients who had clinical benefit with cetuximab, 71% had subsequent clinical benefit with panitumumab therapy. Conclusions: In our single institution analysis of patients who received panitumumab, the number of prior lines of therapy did not significantly affect OS, suggesting that panitumumab retains its efficacy in the 2nd and 3rd line setting. Additionally, panitumumab can benefit patients who previously had clinical benefit with cetuximab.

Clinical outcome of panitumumab for metastatic colorectal cancer with wild-type KRAS status: a meta-analysis of randomized clinical trials

Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that has a favorable effect on patients with metastatic colorectal cancer (mCRC) harboring wild-type (WT) KRAS gene. This meta-analysis was planned to quantify the benefit and assess safety. Selected for the analysis were randomized clinical studies that have used panitumumab-based therapy (PBT) for patients with mCRC and where the outcome of patients with WT KRAS was reported. Four eligible studies were analyzed including 1,010 and 1,105 patients who received PBT and the control intervention, respectively. Used in subsequent-line setting, PBT was associated with 42% improvement in progression-free survival (PFS) (hazard ratio [HR] = 0.58; 95% CI, 0.36-0.93; P = 0.02), a non-significant overall survival (OS) benefit (HR = 0.90; [95% CI, 0.76-1.05]; P = 0.18), and a significant increase in objective response rate (ORR) (odds ratio (OR) = 0.67 [95% CI, 1.15-77.98]; P = 0.04). PBT showed no benefit in the first-line setting. Restricted analysis to two studies (first- and second-line setting), where the treatment effect of PBT was prospectively analyzed according to tumor KRAS status, showed significant PFS (HR = 0.77), OS (HR = 0.84), and ORR (OR = 2.06) advantage. Almost all patients' subgroups attained clinical benefit. PBT-related adverse events were similar across comparisons with the exception of toxicities known to be associated with anti-EGFR therapy. This meta-analysis showed significant clinical benefit for PBT for patients with WT KRAS mCRC predominantly when used following prior chemotherapy exposure. The benefit was demonstrated in most subgroup analyses. Further research to better define potential responders is needed.

Panitumumab: the evidence for its use in the treatment of metastatic colorectal cancer.

Panitumumab is the first fully human monoclonal antibody to Epidermal Growth Factor Receptor (EGFR) to enter clinical trials for the treatment of solid tumors. The anti-tumor activity of panitumumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in numerous cancer models, particularly lung, kidney and colorectal (CRC). Preclinical and clinical studies have established a role for panitumumab in metastatic colorectal cancer (mCRC) refractory to multiple chemotherapeutic regimens. Based on these encouraging findings, panitumumab was approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing mCRC refractory to fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic regimens. The improvement in progression free survival (PFS) and response rate (RR) produced by panitumumab monotherapy was significantly greater in patients with non mutated (wild-type) K-RAS than in those with mutant K-RAS. Therefore implementing routine K-RAS screening and limiting the use of EGFR inhibitors to patients with wild-type K-RAS appears the better strategy for select only the patients who could benefit from the therapy with panitumumab and also may have the potential for cost savings. The purpose of this review was to evaluate the patient-related, disease-related and economic-related evidence for the use of panitumumab in the treatment of metastatic colorectal cancer in clinical practice.

Spotlight on Panitumumab in Metastatic Colorectal Cancer†

Panitumumab (Vectibix) is a recombinant, fully human, IgG2 anti-epidermal growth factor receptor (EGFR) monoclonal antibody. This spotlight reviews the clinical efficacy of intravenous panitumumab in combination with chemotherapy in the first- and second-line treatment of metastatic colorectal cancer and as monotherapy in chemotherapy-refractory metastatic colorectal cancer, as well as summarizing its pharmacologic properties and tolerability. Panitumumab is indicated for use in patients with wild-type rather than mutant KRAS tumors. The efficacy of intravenous panitumumab 6 mg/kg administered every 2 weeks was examined in randomized, open-label, multicenter, phase III trials in patients with metastatic colorectal cancer. When administered as first- or second-line treatment in combination with chemotherapy, panitumumab plus chemotherapy prolonged progression-free survival to a significantly greater extent than chemotherapy alone in patients with wild-type KRAS tumors; no significant between-group difference in overall survival was seen in the second-line treatment trial. In patients with mutant KRAS tumors, progression-free survival was significantly shorter with panitumumab plus oxaliplatin-based chemotherapy (FOLFOX4) than with FOLFOX4 alone in the first-line treatment trial, with no significant difference between patients receiving panitumumab plus irinotecan-based chemotherapy (FOLFIRI) and those receiving FOLFIRI alone in the second-line treatment trial. In chemotherapy-refractory patients with metastatic colorectal cancer, panitumumab monotherapy plus best supportive care prolonged progression-free survival to a significantly greater extent than best supportive care alone in both the overall population and in patients with wild-type KRAS tumors, but not in those with mutant KRAS tumors. Intravenous panitumumab has an acceptable tolerability profile when administered as monotherapy or in combination with chemotherapy. It is associated with the skin-related toxicities characteristic of EGFR inhibitors and appears to have a low risk of immunogenicity. In conclusion, in patients with wild-type KRAS tumors, panitumumab is a useful option in combination with chemotherapy for the first- and second-line treatment of metastatic colorectal cancer or as monotherapy for the treatment of chemotherapy-refractory metastatic colorectal cancer.

Panitumumab in metastatic colorectal cancer

Panitumumab in metastatic colorectal cancer