Clinical UM Guideline

 

Subject: Panitumumab (Vectibix®)
Guideline #: CG-DRUG-66 Publish Date:    12/27/2017
Status: New Last Review Date:    11/02/2017

Description

This document addresses the indications for panitumumab (Vectibix®, Amgen, Thousand Oaks, CA) in the treatment of oncologic conditions.  Panitumumab is a human, IgG2 kappa recombinant, monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR) and inhibits the growth and survival of selected human tumor cells expressing EGFR. 

For additional information, please refer to the following related documents:

Clinical Indications

Medically Necessary:

Panitumumab is considered medically necessary as treatment for individuals who meet all of the following criteria:

  1. As a single agent or as part of combination therapy for Stage IV colon, rectal, colorectal, small bowel, or anal adenocarcinoma; and
  2. Extended RAS gene mutation testing with an FDA approved test is documented and the tumor is determined to be RAS wild-type*; and
  3. Panitumumab is to be used for only one line of therapy; and
  4. Panitumumab is not used in combination with anti-VEGF agents (for example, bevacizumab); and
  5. The individual has not received prior treatment** with cetuximab (Erbitux®, ImClone, Branchburg, NJ).

Notes:
*RAS wild-type means that a genetic mutation in the KRAS, NRAS and BRAF genes is lacking, that is these genes are normal or lacking mutations.
**A course of cetuximab discontinued because of adverse reaction, not progressive disease, is not considered prior treatment.

Not Medically Necessary:

Panitumumab is considered not medically necessary for the treatment of RAS-mutant metastatic colorectal cancer, small bowel or anal adenocarcinoma, (that is, when an FDA approved test has confirmed the presence of genetic mutations in any of the RAS genes) or when RAS mutation status is unknown.

Panitumumab is considered not medically necessary when the above criteria are not met including, but not limited to treatment of penile cancer and squamous cell anal carcinoma.

Panitumumab is considered not medically necessary when used in combination with other monoclonal antibodies or anti-VEGF agents.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

CPT

 

J9303

Injection, panitumumab, 10 mg [Vectibix]

 

 

ICD-10 Diagnosis

 

C17.0-C17.9

Malignant neoplasm of small intestine

C18.0-C18.9

Malignant neoplasm of colon

C19

Malignant neoplasm of rectosigmoid junction

C20

Malignant neoplasm of rectum

C21.0-C21.8

Malignant neoplasm of colon, rectum, rectosigmoid junction, anus

C78.5

Secondary malignant neoplasm of large intestine and rectum

Z51.11-Z51.12

Encounter for antineoplastic chemotherapy and immunotherapy

Z85.038

Personal history of other malignant neoplasm of large intestine

Z85.048

Personal history of other malignant neoplasm of rectum, rectosigmoid junction, and anus

Discussion/General Information

Colorectal carcinoma
Panitumumab is currently one of two intravenous anti-EGFR (epidermal growth factor receptor) therapies approved by the United States (US) Food and Drug Administration (FDA) to treat malignancies.  The monoclonal antibodies directed against EGFR include panitumumab and cetuximab.  Panitumumab binds specifically to EGFR, which inhibits the attachment of ligands.  This prevents the activation of receptor-associated kinases, resulting in the start of apoptosis and inhibition of cell growth.  The blockade of epidermal growth has side effects, with skin rash occurring most frequently.  Various studies have drawn correlations between the frequency and severity of rash to tumor response rate (Giusti, 2007; Lacouture, 2007; Zhu, 2007).

On September 27, 2006, the FDA provided an accelerated approval for panitumumab (Vectibix) as a treatment of EGFR-expressing metastatic colorectal carcinoma (mCRC) with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.  The approval was based on progression-free survival (PFS) data from a randomized controlled trial (RCT) involving 463 individuals with mCRC.  Individuals had been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, but progressed on or following therapy.  There was a statistically significant PFS prolongation of 96 days with panitumumab compared to 60 days with best supportive care (BSC).  Nineteen (8%) partial response rates with a median duration of 17 weeks were noted in individuals randomized to receive panitumumab.  There were no measurable responses in the control arm (Van Cutsem, 2007; Product Information Label, 2014). 

The product information label was updated in June 2008, indicating panitumumab as a single agent for the treatment of EGFR-expressing mCRC that has progressed despite standard chemotherapy.  Additional warnings were added to the label in 2009, stating there has been increased toxicity with combination chemotherapy.  The 2009 label update also included an updated recommendation that, due to a lack of benefit, panitumumab was not indicated for mCRC with KRAS mutation in codon 12 or 13.  The limitation of use was further amended in 2012, stating panitumumab was not indicated for treatment of individuals with KRAS-mutant mCRC or unknown KRAS-mutation status.  A new indication as first-line treatment, in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin), of individuals with wild-type KRAS (exon 2 in codons 12 or 13) mCRC, as determined by an FDA-approved test, was added to the label in May of 2014. 

The Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) study (Hecht, 2009) was a phase IIIb randomized, open-label clinical trial evaluating cohorts of a chemotherapy regimen including bevacizumab, with and without panitumumab, as first-line treatment of individuals with previously untreated mCRC.  Investigators chose a 5-FU-, leucovorin- and oxaliplatin-based regimen (Ox-CT; n=823) or a 5-FU-, leucovorin- and irinotecan-based regimen (Iri-CT; n=230), each with bevacizumab.  Individuals were randomized to receive the selected regimen, or chemotherapy with the addition of panitumumab.  A statistically significant difference in PFS in favor of the control arm (without panitumumab) was unveiled at the first planned interim analysis (Zhu, 2007) which resulted in a discontinuation of panitumumab, and the study was discontinued early based on this data.  In the final analysis of the data, the median PFS was 10.1 months for panitumumab and 11.7 months for the control group (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.79 to 1.79) (Hecht, 2009).  In a safety analysis of 804 individuals in the Ox-CT cohort and 224 individuals in the Iri-CT cohort, both groups had more adverse events (AE) of grade 3 or higher in the panitumumab cohorts compared to the control groups (Ox-CT 367 [90%] versus 305 [77%], respectively; Iri-CT 100 [90%] versus 71 [63%] respectively).  Serious AEs included diarrhea, infections and pulmonary embolism.  Seven (1%) deaths were attributed to be panitumumab related.  The authors concluded the decreased PFS and increased serious AEs do not support panitumumab in combination with bevacizumab and oxaliplatin- or irinotecan-based chemotherapy as a treatment for mCRC.  “Administration of chemotherapy and dual EGFR/VEGF inhibition should be conducted only in a research setting” (Hecht, 2009).

The National Comprehensive Cancer Network® (NCCN®) colon and rectal Clinical Practice Guidelines in Oncology (2017) state, “Strongly recommends against the use of therapy involving the concurrent combination of an anti-EGFR agent (cetuximab or panitumumab) and an anti-vascular endothelial growth factor (VEGF) agent (bevacizumab).” 

The phase III, Panitumumab Randomized Trial in Combination with Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) study randomized 1183 individuals with untreated mCRC to either a regimen of FOLFOX4 or to FOLFOX4 plus panitumumab.  The primary endpoint was PFS.  A total of 1096 (93%) of the participants had KRAS information available.  No KRAS mutations in exon 2 were noted in 656 participants (60%) and KRAS mutations in exon 2 were noted in 440 individuals (40%).  PFS was significantly improved in those with wild-type (WT) KRAS and who were treated with FOLFOX4 + panitumumab versus FOLFOX4 alone (median PFS 9.6 months vs. 8.0 months; HR, 0.80; 95% CI, 0.66 to 0.97; p=0.02).  There was a nonsignificant improvement in overall survival of 4.2 months (23.9 vs. 19.7 months, p=0.07) for those treated with FOLFOX4 + panitumumab vs. FOLFOX4 alone.  Participants with mutant KRAS had PFS significantly reduced with the addition of panitumumab to FOLFOX4 compared to FOLFOX4 alone (median PFS 7.3 months vs. 8.8 months; HR, 1.29; 95% CI, 1.04 to 1.62; p=0.02) (Douillard, 2010). 

The medically necessary criteria for excluding previous use of EGFR monoclonal antibody therapy prior to treatment with panitumumab is based on the selection criteria in the pivotal trial, as well as the expert view of medical practitioners practicing in the clinical area of oncology, and who have familiarity with the available evidence. The NCCN® Clinical Practice Guidelines in Oncology for colon cancer and rectal cancer (2017) include the following clarification:

There are no data, nor is there a compelling rationale, to support the use of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab.  As such, the use of one of these agents after therapeutic failure on the other is not recommended. 

Price and colleagues (2014) reported results from the first direct comparison trial which was an open-label, randomized, multi-center phase III study that compared panitumumab to cetuximab in individuals with chemotherapy-refractory mCRC.  A total of 1010 individuals were enrolled with 999 actually starting treatment.  The panitumumab treatment group included 499 participants with 500 participants assigned to the cetuximab treatment group.  The primary endpoint of overall survival (OS) showed panitumumab was noninferior to cetuximab (p=0.0007).  The median OS was 10.4 months in the panitumumab group and 10.0 months in the cetuximab group (HR, 0.97; 95% CI, 0.84-1.11).  The incidence of AE was generally similar.  The noted differences were a lower occurrence rate of grade 3-4 infusion reaction with panitumumab (< 0.5%) compared to cetuximab (2%) and a higher occurrence rate of grade 3-4 hypomagnesaemia with panitumumab (7%) compared to the cetuximab (3%) cohorts.  The authors concluded that although the results suggest noninferiority between the two anti-EGFR monoclonal antibodies, the study did not “Directly address the sequencing and timing of therapy” and additional research is needed.  Additional studies are also needed to confirm the interchangeability of anti-EGFR monoclonal antibodies in other clinical indications.

Recommendations by the NCCN (V.2.2017) regarding the use of panitumumab and the other FDA approved EGFR inhibitor cetuximab in the treatment of colorectal cancer note there are no data, nor is there a compelling rationale to support the use of one of these agents after the therapeutic failure of the other and that this practice is not recommended.  The NCCN practice guideline (V.2.2017) notes skin toxicities are side effects for both cetuximab and panitumumab, and is not considered to be an infusion reaction.  In addition, the guidelines indicate that EGFR testing of colorectal tumor cells has not demonstrated predictive value in determining the likelihood of a response to panitumumab.  Thus, this testing is not required to establish medical necessity or to be used in treatment determinations.

Panitumumab is indicated for individuals with tumors that express the wild-type KRAS gene.  The American Society of Clinical Oncology (ASCO, Allegra, 2009) issued a provisional, consensus clinical opinion based on systematic reviews of literature primarily from phase II and III clinical trials involving individuals with mCRC: 

All patients with metastatic colorectal carcinoma who are candidates for anti-EGFR antibody therapy should have their tumor tested for KRAS mutations in a CLIA-accredited laboratory.  If KRAS mutation in codon 12 or 13 is detected, then patients with metastatic colorectal carcinoma should not receive anti-EGFR antibody therapy as part of their treatment.

The ASCO published a provisional opinion update in 2016 regarding extended RAS mutation testing in mCRC to predict response to anti-EGFR monoclonal antibody therapy.  The opinion was based on evidence from 13 articles on KRAS mutations (11 systematic reviews, 2 health technology assessments) and 2 articles on NRAS testing.  The opinion stated that:

Subgroup analyses of patients with any of the less common RAS mutations are small, and there is inadequate evidence to provide a definitive opinion on the lack of benefit for the use of anti-EGFR antibodies for patients whose cancer harbors any specific RAS mutation other than the exon 2 KRAS mutation (Allegra, 2016).

Studies of mCRC treatment have shown there are subsets of individuals who are not as responsive to anti-EGFR monoclonal antibodies.  To understand the variation, there is ongoing research into the genetic signaling pathways that promote the growth of specific cells.  The Kirsten rat sarcoma virus also known as the KRAS gene is being analyzed for mutations and correlation of response to anti-EGFR monoclonal antibodies.  The desired goal for KRAS status mutation analysis is to identify individuals who would not respond to anti-EGFR monoclonal antibody therapy, thereby saving them the time, expense and unnecessary toxicity of ineffective therapies.

Freeman and colleagues (2008) analyzed gene mutations in mCRC tumor samples from three phase II panitumumab studies.  Results favored PFS in individuals with wild-type KRAS compared with individuals with mutant KRAS (HR 0.4; 95% CI, 0.2-0.7; p=0.002).  Median PFS was 16.2 weeks for the wild-type KRAS versus 7.4 weeks for the mutant KRAS cohort.  In a systematic review and meta-analysis, Adelstein and colleagues (2011) analyzed the treatment effect of KRAS mutation in response to anti-EGFR antibodies to treat mCRC.  Data analyzed from 11 studies included 8924 individuals treated with anti-EGFR therapy.  With anti-EGFR therapy, the HR for progressive disease in individuals with KRAS wild-type was 0.80 (4436 individuals; 95% CI, 0.64, 0.99) and 1.11 (3119 individuals; 95% CI, 0.97, 1.27) in individuals with the mutant KRAS.  The authors concluded the status of KRAS mutation modified the treatment effect of anti-EGFR therapy in the treatment of mCRC.

In a prospective-retrospective analysis of the PRIME study, Douillard and colleagues (2013) investigated if other activating RAS mutations, besides the KRAS mutation in exon 2, may be negative predictive biomarkers for anti-EGFR therapy.  The updated analysis showed a significant improvement in overall survival of 4.4 months (23.8 months vs. 19.4 months, p=0.03) in those treated with FOLFOX4 + panitumumab vs. FOLFOX4 alone.  In this exploratory analysis, RAS status had been evaluated in 90% (1060 participants) of the total 1183 participants in the PRIME trial.  There were 512 (48%) individuals who had non-mutated RAS, which meant no KRAS or NRAS mutations in exons 2, 3, or 4.  Mutated RAS (any KRAS or NRAS mutations in exon 2, 3, or 4) were identified in 548 (52%) participants.  A total of 108 (17%) of individuals without mutated KRAS in exon 2 had other RAS mutations in other exons.  This subgroup of participants had non-significantly shorter PFS and OS in the panitumumab + FOLFOX4 treatment group compared to the FOLFOX4 cohort.  The authors note the data, “Further assesses the hypothesis that additional activating RAS mutations predict unresponsiveness to panitumumab treatment.”  However, these findings need to be confirmed with meta-analyses or pooled trial data of anti-EGFR therapy. 

NCCN guidelines for colon cancer (V.2.2017) recommends:

All patients with mCRC should have tumor tissue genotyped for RAS mutations (KRAS, NRAS) and BRAF mutations.  Patients with any known KRAS mutation (exon 2 or non-exon 2) or NRAS mutation should not be treated with either cetuximab or panitumumab.  BRAF V600E mutation makes response to panitumumab or cetuximab highly unlikely…The testing can be performed on the primary colorectal cancers and/or on the metastasis as literature has shown that KRAS, NRAS and BRAF mutations are similar in both specimen types.

The data suggest that the mCRC population with wild-type Extended RAS mutation status benefited more from panitumumab alone, as compared to those with the activating RAS mutations (that is, a genetic mutation in the KRAS, NRAS, or BRAF genes).  Therefore, analysis of RAS status is recommended to facilitate treatment plans.

Squamous cell anal cancer is the most common histologic form of anal cancer. Adenocarcinoma and melanoma of the anal canal represents infrequently occurring subtypes of anal cancer.  The NCCN Anal Carcinoma Clinical Practice Guideline (V.2.2017) recommends management of anal adenocarcinoma according to the NCCN Rectal Cancer Clinical Practice Guidelines (V.2.2017).  Specialty consensus opinion also supports the NCCN recommendations to treat stage IV anal adenocarcinoma similar to stage IV colorectal adenocarcinoma.  Of note, the NCCN guidelines do not recognize the use of panitumumab for treatment of squamous cell anal cancer as an off-label indication.

Other carcinomas
The updated National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology for penile cancer (V.2.2017) no longer include the off-label recommendation for panitumumab as a single agent in second-line therapy as palliative therapy.  The guidelines recommend clinical trials for second-line or palliative therapies as “No standard second-line systemic therapy exists.”

Waddell and colleagues (2013) investigated panitumumab as first-line therapy for advanced esophagogastric carcinoma in a phase III open label trial known as REAL3.  Participants were randomized to epirubicin, oxaliplatin, and capecitabine (EOC) or to a modified dose EOC with panitumumab (mEOC+P).  The primary endpoint was OS.  However, after a preplanned review by the independent data monitoring committee reported a decreased OS with panitumumab compared to EOC alone, the trial was halted.  Additionally, there was an increased incidence of AEs with the panitumumab regimen, which included grade 3 and 4 diarrhea, mucositis, rash and hypomagnesemia.  Based on the inferior OS and PFS, the authors concluded that panitumumab could not be recommended when combined with EOC in unselected individuals with advanced esophagogastric adenocarcinoma.  Additional investigation was recommended for biomarkers that may identify a subgroup who may benefit from panitumumab.

A phase III study investigating cisplatin and fluorouracil with or without panitumumab as a treatment for individuals with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM) was reported by Vermorken (2013).  A total of 327 individuals were randomized to the panitumumab treatment group and 330 were assigned to the control group.  The primary endpoint of the open-label study was OS.  The median OS for the panitumumab cohort was 11.1 months compared to 9.0 months in the control group (HR, 0.873; 95% CI, 0.729-1.046; p=0.1403).  There were 14 (4%) deaths in the treatment group, with 5 (2%) deaths attributed to panitumumab.  In the control, group, there were 8 (2%) treatment related deaths.  The authors concluded that the addition of panitumumab to chemotherapy did not improve OS. 

In 2015, two open-label, randomized, controlled, phase II trials were reported addressing the use of panitumumab for unresected, locally advanced, squamous-cell carcinoma of the head and neck.  The first, reported by Mesia, the CONCERT-1 trial,  involved 150 subjects aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous cell carcinoma of the head and neck (non-nasopharyngeal) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.  Subjects were randomly assigned in a 2:3 ratio to receive treatment with either open-label chemoradiotherapy (n=63; 3 cycles of cisplatin at 100 mg/m2) or panitumumab plus chemoradiotherapy (n=87; 3 cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin at 75 mg/m2).  At 2 years, local-regional control was reported to be 68% (95% CI, 54-78) in the chemoradiotherapy group and 61% (95% CI, 50-71) in the panitumumab plus chemoradiotherapy group.  The most frequent grade 3-4 AE were dysphagia (27% of subjects in the chemoradiotherapy group vs. 40% in the panitumumab plus chemoradiotherapy group), mucosal inflammation (24% vs. 55%, respectively), and radiation skin injury (13% vs. 31%, respectively).  Serious AE were reported in 32% of subjects in the chemoradiotherapy group vs. 43% of subjects in the panitumumab plus chemoradiotherapy group.  The authors concluded that the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit.

The second report, by Giralt, provided results of the CONCERT-2 trial. This trial used the same inclusion and exclusion criteria as the CONCERT-1 trial but involved randomly assigning subjects in a 2:3 ratio to either chemoradiotherapy (n=61; 2 cycles of cisplatin at 100 mg/m2 during radiotherapy) or to radiotherapy plus panitumumab (n=90; 3 cycles of panitumumab at 9 mg/kg every 3 weeks administered with radiotherapy).  The authors reported that local-regional control at 2 years was 61% (95% CI, 47-72) in the chemoradiotherapy group and 51% (95% CI, 40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 AE were mucosal inflammation (40% of subjects in the chemoradiotherapy group vs. 42% of subjects in the radiotherapy plus panitumumab group), dysphagia (20% vs. 40%, respectively), and radiation skin injury (11% vs. 24%, respectively).  Serious AE were reported in 40% of subjects in the chemoradiotherapy group vs. 34% of subjects in the radiotherapy plus panitumumab group.  The authors concluded that panitumumab cannot replace cisplatin in combined treatment with radiotherapy.

There are ongoing trials studying the expanded use of panitumumab for additional indications, such as solid tumors including lung cancer, and at different stages of various diseases.  The use of panitumumab in combination with a variety of chemotherapy or biologic agents is also under investigation.

Black box warnings from the FDA Product Information Label for Vectibix (2017) include the following:

Dermatologic Toxicity
Dermatologic toxicities occurred in 90% of individuals and were severe (NCI-CTC grade 3 and higher) in 15% of individuals receiving monotherapy.  Monitor individuals who develop dermatologic or soft tissue toxicities while receiving panitumumab for the development of inflammatory or infectious sequelae. Life threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in individuals treated with Vectibix.  It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis).  Withhold or discontinue Vectibix for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications.

Additional labeling updates, warnings, precautions and recommendations from the FDA Product Information Label (2017) include the following:

Increased Tumor Progression, Increased Mortality or Lack of Benefit in Patients with RAS-mutant mCRC 
In June 2017 the FDA approved a supplemental Biologics License Application (sBLA) for Vectibix (panitumumab) for subjects with wild-type RAS (defined as lacking mutations in both KRAS and NRAS genes), as determined by an FDA-approved test* for this use: mCRC.
Indications:

Limitation of Use:

Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab).  Anti-EGFR antibodies in individuals with tumors containing RAS mutations resulted in exposing those subjects to anti-EGFR related AE reactions without clinical benefit from these agents.  Additionally, in Study 20050203, 272 subjects with RAS-mutant mCRC tumors received Vectibix in combination with FOLFOX and 276 subjects received FOLFOX alone.  In an exploratory subgroup analysis, OS was shorter (HR=1.21, 95% CI: 1.01-1.45) in subjects with RAS-mutant mCRC who received Vectibix and FOLFOX versus FOLFOX alone.

Definitions

Adenocarcinoma: Cancer originating in cells that line specific internal organs and that have gland-like (secretory) properties.

Anal cancer: Cancer originating in the tissues of the anus; the anus is the opening of the rectum (last part of the large intestine) to the outside of the body.

Apoptosis: A series of molecular steps resulting in a type of cell death; the body’s normal way of getting rid of unneeded or abnormal cells; programmed cell death.

Colon cancer: Cancer originating in the tissues of the colon (the longest part of the large intestine).  Most colon cancers are adenocarcinomas that begin in cells that make and release mucus and other fluids.

Colorectal cancer: Cancer originating in the colon (the longest part of the large intestine) or the rectum (the last several inches of the large intestine before the anus).

In Vitro Companion Diagnostic Devices (IVD): An in vitro device or an imaging tool that provides information essential for the safe and effective use of a corresponding therapeutic product. The use of an IVD companion diagnostic device with a particular therapeutic product is stipulated in the instructions for use in the FDA labeling of both the diagnostic device and the corresponding therapeutic product, as well as in the FDA labeling of any generic equivalents and biosimilar equivalents of the therapeutic product (FDA, 2017).

KRAS or NRAS wild-type: The combination of KRAS and NRAS genes is referred to as RAS wild type. Extended RAS mutation refers to mutations in KRAS, NRAS or BRAF genes. Wild-type is a term that refers to the normal or non-mutant form of the RAS genes, as distinguished from any mutant forms of KRAS, NRAS or BRAF where a genetic mutation is present.

Line of therapy:

Metastatic: The spread of cancer from one part of the body to another. A metastatic tumor contains cells that are like those in the original (primary) tumor and have spread.

Monoclonal antibody: A protein developed in the laboratory that can locate and bind to a specific substance in the body and on the surface of cancer cells (NCI, 2014).

Off-label: Utilization of a United States Food and Drug Administration (FDA) approved drug for uses other than those listed in the FDA approved label.

Partial response: A decrease in the size of a tumor, or in the amount of cancer in the body, resulting from treatment; also called partial remission.

Rectal cancer: Cancer originating in tissues of the rectum (the last several inches of the large intestine closest to the anus).

References

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  26. Schuette W, Behringer D, Stoehlmacher J, et al. CHAMP: A Phase II study of panitumumab with pemetrexed and cisplatin versus pemetrexed and cisplatin in the treatment of patients with advanced-stage primary nonsquamous non-small-cell lung cancer with particular regard to the KRAS status. Clin Lung Cancer. 2015; 16(6):447-456.
  27. Seymour MT, Brown SR, Middleton G, et al. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomized trial. Lancet Oncol. 2013; 14(8):749-759.
  28. Tebbutt NC, Price TJ, Ferraro DA, et al. Panitumumab added to docetaxel, cisplatin and fluoropyrimidine in esophagogastric cancer: ATTAX3 phase II trial. Br J Cancer. 2016; 114(5):505-509.
  29. Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007; 25(13):1658-1664.
  30. Van Cutsem E, Siena S, Humblet Y, et al. An open-label, single-arm study assessing safety and efficacy of panitumumab in patients with metastatic colorectal cancer refractory to standard chemotherapy. Ann Oncol. 2007; 19(1):92-98.
  31. Vermorken JB, Stöhlmacher-Williams J, Davidenko, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomized trial. Lancet Oncol. 2013; 14(8):697-710.
  32. Zhu Z. Targeted cancer therapies based on antibodies directed against epidermal growth factor receptor: status and perspectives. Acta Pharmacol Sin. 2007; 28(9):1476-1493.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Allegra CJ, Jessup JM, Somerfield MR, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009; 27(12):2091-2096.
  2. Allegra CJ, Rumble RB, Hamilton SR, et al. Extended RAS gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015. J Clin Oncol. 2016; 34(2):179-185.
  3. American Hospital Formulary Service® (AHFS). AHFS Drug Information 2017®. Bethesda, MD: American Society of Health-System Pharmacists®, 2017.
  4. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). KRAS mutations and epidermal growth factor receptor inhibitor therapy in metastatic colorectal cancer. TEC Assessments. 2008; 23(6).
  5. Evaluation of Genomic Applications in practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy? Genet Med. 2013; 15(7):517-527.
  6. Medical Advisory Secretariat. KRAS testing for anti-EGFR therapy in advanced colorectal cancer. An evidence-based and economic analysis. Ont Health Technol Assess Ser [Internet]. December 2010. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377508/pdf/ohtas-10-49.pdf. Accessed on September 21, 2017.
  7. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium (electronic version). For additional information: http://www.nccn.org. Accessed on September 21, 2017.
  8. NCCN Clinical Practice Guidelines in Oncology™. © 2017 National Comprehensive Cancer Network, Inc. For additional information: http://www.nccn.org/index.asp. Accessed on September 21, 2017.
    • Anal Carcinoma (V.2.2017). Revised April 20, 2017.
    • Colon Cancer (V.2.2017). Revised March 13, 2017.
    • Penile Cancer (V.2.2017). Revised March 10, 2017. 
    • Rectal Cancer (V.3.2017). Revised March 13, 2017.
  9. Panitumumab. In: DrugPoints System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated August 29, 2017. Available at: http://www.micromedexsolutions.com. Accessed on September 28, 2017.
  10. U.S. Food and Drug Administration (FDA). Office of In Vitro Diagnostics and Radiological Health. Accessed on September 22, 2017.
  11. Vectibix (Panitumumab) [Prescribing Information], Thousand Oaks, CA. Amgen. June, 2017. Available at:  https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125147s207lbl.pdf. Accessed on September 21, 2017.
  12. Vectibix (Panitumumab) Injectable Drug Approval Package. May 29, 2007. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125147s0000TOC.cfm. Accessed on September 21, 2017.
Websites for Additional Information
  1. American Cancer Society. What is colorectal cancer? Last revised April 6, 2017. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003047-pdf.pdf. Accessed on. September 23, 2017.
  2. American Cancer Society. Cancer Immunotherapy. Monoclonal antibodies to treat cancer. Last revised 08/08/2016. Available at: http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-monoclonal-antibodies. Accessed on September 23, 2017.
  3. National Cancer Institute. Dictionary of Cancer Terms. Monoclonal Antibodies. Available at: http://www.cancer.gov/. Accessed on September 23, 2017.
  4. National Library of Medicine. Genetics Home Reference. KRAS. Reviewed May 2016. Available at: http://ghr.nlm.nih.gov/gene/KRAS. Accessed on September 23, 2017.
Index

Epidermal Growth Factor Receptor (EGFR)
Erbitux
Monoclonal Antibody
Panitumumab
Vectibix

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

New

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review.

New

11/01/2017

Hematology/Oncology Subcommittee review. Initial document development. Moved content of DRUG.00035 Panitumumab (Vectibix®) to new clinical utilization management guideline document with the same title. Clarified the terminology regarding RAS wild type to include test verification of no “Extended RAS” mutations (including KRAS, NRAS, and BRAF mutations) in the MN criteria for panitumumab.  Added a NMN statement for panitumumab when mutations are present in any of the RAS genes or when RAS status is unknown.