Coverage Policy Manual
Policy #: 2017024
Category: Pharmacy
Initiated: June 2017
Last Review: July 2023
  Panitumumab (e.g., Vectibix™)
Description:
Panitumumab is a fully human immunoglobulin G2 antibody, that binds to human epidermal growth factor receptor (EGFR on the extracellular domain.  This binding inhibits the growth and survival of cancer cells that express EGFR, by causing internalization of the receptor and preventing further activation, which subsequently inhibits signaling for a variety of cellular events.  (Clinical Pharmacology, 2017).  
 
Regulatory Status
 
Vectibix™ was FDA-approved in 2006. (U.S.Food and Drug Administration 2015).
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.
 
Effective January 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Panitumumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of colorectal cancer when the following criteria is met:
 
    1. First-line treatment of wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC) in combination with FOLFOX. (FDA, 2021)
2. As a single agent for the treatment of wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC) following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. (FDA, 2021)
3. Therapy for KRAS/NRAS/BRAF wild-type gene and left-sided only tumors in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen in individuals appropriate for intensive therapy:
a. As primary treatment of colon cancer for locally unresectable or medically inoperable disease (NCCN 2A)
b. As primary treatment of rectal adenocarcinoma for T3, N Any; T1-2, N1-2; T4, N Any; or locally unresectable or medically inoperable disease if resection is contraindicated following neoadjuvant or total neoadjuvant therapy (NCCN 2A)
c. For unresectable synchronous liver and/or lung metastases that remain unresectable after primary systemic therapy (NCCN 2A)
d. For rectal adenocarcinoma following palliative radiation therapy (RT) or chemo/RT for synchronous liver only and/or lung only metastases that are unresectable or medically inoperable and remain unresectable (with progression of primary tumor) after primary systemic therapy (NCCN 2A)
e. As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction (NCCN 2A)
f. For synchronous unresectable metastases of other sites (NCCN 2A)
g. As primary treatment for unresectable metachronous metastases in individuals who have not received previous adjuvant FOLFOX or CapeOXwithin the past 12 months, who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy, or who have not received any previous chemotherapy (NCCN 2A)
h. For unresectable metachronous metastases that remain unresectable after primary treatment (NCCN 2A)
i. And progressed on non-intensive therapy, except if received previous fluoropyrimidine, with improvement in functional status (NCCN 2A)
4. Primary treatment for unresectable synchronous liver and/or lung metastases (KRAS/NRAS/BRAF wild-type gene and left-sided tumors only) in combination with:
a. FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen (NCCN 2A)
b. FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen (NCCN 2A)
5. Primary treatment for individuals with unresectable metachronous metastases (KRAS/NRAS/BRAF wild-type gene) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months:
a. In combination with irinotecan (NCCN 2A)
b. In combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen (NCCN 2A)
6. Primary treatment in combination with encorafenib for individuals with unresectable metachronous metastases (BRAF V600E mutation positive) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months (NCCN 2A)
7. Subsequent therapy for progression of advanced or metastatic disease (KRAS/NRAS/BRAF wild-type only):
a. In combination with irinotecan, FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen, or as a single agent for individuals who cannot tolerate irinotecan, if previously treated with oxaliplatin-based therapy without irinotecan (NCCN 2A)
b. In combination with irinotecan, FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen, or as a single agent for individuals who cannot tolerate irinotecan, if previously treated with irinotecan-based therapy without oxaliplatin (NCCN 2A)
c. In combination with irinotecan or as a single agent for individuals who cannot tolerate irinotecan if previously treated with oxaliplatin and irinotecan (NCCN 2A)
d. In combination with irinotecan or as a single agent for individuals who cannot tolerate irinotecan if previously treated without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab (NCCN 2A)
8. Subsequent therapy in combination with encorafenib for progression of advanced or metastatic disease (BRAF V600E mutation positive) in individuals previously treated:
a. With oxaliplatin-based therapy without irinotecan (NCCN 2A)
b. With irinotecan-based therapy without oxaliplatin (NCCN 2A)
c. With treatment with oxaliplatin and irinotecan (NCCN 2A)
d. Without irinotecan or oxaliplatin (NCCN 2A)
e. Without irinotecan or oxaliplatin followed by FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) with or without bevacizumab (NCCN 2A)
 
The use of this drug is covered if an FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
Dosing per FDA Guidelines
 
    • 6 mg/kg every 14 days
    • Panitumumab is available as 100 mg/5 mL (20 mg/mL) and 400 mg/20 mL (20 mg/mL) in single-dose vials.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Panitumumab does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication or circumstance other than those not listed above.
 
For members with contracts without primary coverage criteria, Panitumumab for any indication or circumstance other than those not listed above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective prior to January 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
 
Panitumumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications:
 
    • Metastatic Colorectal Cancer, for wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use:
        • in combination with FOLFOX for first-line treatment OR  
        • as a single agent following disease progression after prior treatment with fluoropyrimidine, oxaplatin, and irinotecan-containing chemotherapy.
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and administration
 
      • 6 mg/kg every 14 days.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Panitumumab (Vectibix®) does not meet member benefit certificate primary coverage criteria for any other indication than listed above.
 
For members with contracts without primary coverage criteria, Panitumumab (Vectibix®) is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective July 2019 to June 2021
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
 
Panitumumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications:
 
    • Metastatic Colorectal Cancer, for wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use:
        • in combination with FOLFOX for first-line treatment OR  
        • as a single agent following disease progression after prior treatment with fluoropyrimidine, oxaplatin, and irinotecan-containing chemotherapy.
 
NCCN 1, 2A, and 2B recommendations in accordance with Coverage Policy #2000030.
 
Dosage and administration
      • 6 mg/kg every 14 days.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Panitumumab (Vectibix®) does not meet member benefit certificate primary coverage criteria for any other indication than listed above.
 
For members with contracts without primary coverage criteria, Panitumumab (Vectibix®) is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective July 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
 
Panitumumab meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the following indications:
 
    • Metastatic Colorectal Cancer, for wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use:
        • in combination with FOLFOX for first-line treatment OR
        • as a single agent following disease progression after prior treatment with fluoropyrimidine, oxaplatin, and irinotecan-containing chemotherapy
    • NCCN 2A and 2B Recommendations in accordance with Coverage Policy #2000030.
 
Dosage and administration
 
    • Administer 6 mg/kg every 14 days IV over 60 minutes (<1000 mg) or 90 minutes (.1000mg).
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Panitumumab (Vectibix®) does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, Panitumumab (Vectibix®) is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to July 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage
Criteria
 
Panitumumab meets primary coverage criteria and is covered for treatment for the following listed indications:
 
FDA labeled
 
COLORECTAL CANCER, for wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use:
    • in combination with FOLFOX for first-line treatment OR
    • as a single agent following disease progression after prior treatment with fluoropyrimidine, oxaplatin, and irinotecan-containing chemotherapy
 
 
Off-label (2017)
 
COLON CANCER:
 
     A.  Left-sided only tumors expressing KRAS/NRAS wild-type gene, therapy:
      • in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) OR
      • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen OR
      • as a single agent in patients not appropriate for intensive therapy
 
        1. as primary treatment for locally unresectable or medically inoperable disease OR
        2. for unresectable synchronous liver and/or lung metastases OR
        3. as primary treatment for synchronous abdominal/peritoneal metastases OR
        4. for unresectable synchronous metastases of other sites OR
        5. as primary treatment for unresectable metachronous metastases OR
        6. for unresectable metachronous metastases that remain unresectable after primary treatment
  
B. Initial treatment for unresectable synchronous Liver and/or Lung Metastases from Left-sided only tumors expressing KRAS/NRAS wild-type gene:
      • in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) regimen OR
      • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
 
C. Adjuvant therapy for Left-sided only tumors expressing KRAS/NRAS wild-type gene, therapy:
      • in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) OR
      • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen, OR  
      • as a single agent in patients not appropriate for intensive therapy
  
        1. as adjuvant treatment following resection for synchronous Liver and/or Lung Metastases OR
        2. as adjuvant treatment following resection and/or local therapy for resectable Metachronous Metastases OR
        3. as adjuvant treatment for Metachronous Metastases that converted from unresectable to resectable disease
 
D. Primary treatment for tumors expressing KRAS/NRAS wild-type gene for patients with unresectable Metachronous Metastases
      • in combination with irinotecan OR
      • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
  
E. Subsequent therapy following disease progression for unresectable advanced or metastatic disease from tumors expressing KRAS/NRAS wild-type gene not previously treated with cetuximab or panitumumab
      • in combination with irinotecan OR
      • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
 
 
RECTAL CANCER:
 
    A. Tumors expressing KRAS/NRAS wild-type gene:
      • in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) OR
      • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen, OR  
      • as a single agent in patients not appropriate for intensive therapy
 
        1. primary treatment for locally unresectable or medically inoperable disease with no metastases OR
        2. primary treatment for unresectable Synchronous Metastases OR
        3. primary treatment for unresectable Metachronous Metastases OR
        4. systemic therapy following primary treatment with chemoradiation or local therapy for symptomatic unresectable Synchronous Metastases or medically inoperable disease OR
        5. systemic therapy for unresectable Metachronous Metastases that remain unresectable after primary treatment
        6. adjuvant treatment (following resection and/or local therapy) for resectable Metachronous Metastases in patients who have received previous chemotherapy OR
        7. adjuvant treatment for Metachronous Metastases that converted from unresectable to resectable disease  
 
 
B. Primary treatment for tumors expressing KRAS/NRAS wild-type gene in patients with unresectable Metachronous Metastases
      • in combination with irinotecan  
 
C.  Subsequent therapy following disease progression for unresectable advanced or metastatic disease from tumors expressing KRAS/NRAS wild-type gene not previously treated with cetuximab or panitumumab:
      • in combination with irinotecan OR
      • in combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan) regimen
 
 
Dosing:
The prescribed regimen must be in compliance with FDA-approved dosing, with a dosing regimen of less than 6mg/kg ever 2 weeks
 
Panitumumab is given as an IV infusion over 60 minutes.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary
Coverage Criteria
 
The use of Panitumumab for the treatment of any other indications or any other circumstances than those outlined above does not meet member benefit certificate primary coverage criteria.
 
For members with contracts without primary coverage criteria, the use of Panitumumab for the treatment of any other indications or any other circumstances than those outlined above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Rationale:
On September 27, 2006, the U.S. Food and Drug Administration granted approval to panitumumab (Vectibix, Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens (Gusti et al, 2007). Panitumumab approval was based on the results of a single, open-label, randomized, multinational study that enrolled 463 patients with EGFR-expressing (at least 1+ membrane staining in > or =1% of tumor cells) metastatic colorectal cancer. Patients were randomized to either best supportive care (BSC) alone or BSC plus panitumumab, 6 mg/kg i.v., every other week. The primary study endpoint was progression-free survival (PFS), determined by an independent review committee that was blinded as to treatment assignment. BSC patients who progressed were eligible to receive panitumumab. The study patients' median age was 62 years, with 40% aged > or =65; 63% were male, 99% were white, 86% had a baseline Eastern Cooperative Oncology Group performance status score of 0 or 1, and 67% had colon cancer. The median time from diagnosis of metastases was approximately 19 months and the median number of prior therapies was 2.4. The PFS duration was significantly longer among patients randomized to receive panitumumab in addition to BSC (n = 231) compared with BSC alone (n = 232). The median and mean PFS times were 56 and 96.4 days, respectively, for patients receiving panitumumab and 51 and 59.7 days, respectively, for patients receiving BSC alone. Nineteen partial responses (8%, 95% confidence interval [CI], 5.3%-12.5%) were observed in panitumumab treated patients. The median duration of response was 17 weeks (95% CI, 16-25 weeks). Approximately 75% of patients in the BSC alone arm crossed over to receive panitumumab after disease progression. There was no difference in overall survival between the two study arms. The most common adverse events were skin rash, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea. The most serious adverse events were pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, diarrhea, and constipation.
 
Price et al (2014) conducted a multicenter, multi-national, randomized, open-label, phase 3 head-to-head study referred to as the ASPECCT trial that compared panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 mCRC.   Enrollment was 1010 patients aged 18 years or older, 999 of whom began study treatment: 499 received panitumumab and 500 received cetuximab. Using a computer-generated randomisation sequence, patients were assigned (1:1; stratified by geographical region and ECOG performance status, with a permuted block method) to receive panitumumab (6 mg/kg once every 2 weeks) or cetuximab (initial dose 400 mg/m(2); 250 mg/m(2) once a week thereafter). The primary endpoint was overall survival assessed for non-inferiority (retention of ≥ 50% of the cetuximab treatment effect; historical hazard ratio [HR] for cetuximab plus best supportive care vs best supportive care alone of 0.55). The primary analysis included patients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment. For the primary analysis of overall survival, panitumumab was non-inferior to cetuximab (Z score -3.19; p=0.0007). Median overall survival was 10.4 months (95% CI 9.4-11.6) with panitumumab and 10.0 months (9.3-11.0) with cetuximab (HR 0.97; 95% CI 0.84-1.11). Panitumumab retained 105.7% (81.9-129.5) of the effect of cetuximab on overall survival seen in this study. The incidence of adverse events of any grade and grade 3-4 was similar across treatment groups.
 
Douillard et al (2010) conducted a multicenter, phase III trial referred to as the PRIME study.  In the study, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status. KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy.
 
Boeckx et al (2016) presented the results of a retrospective analyses with panitumumab in mCRC patients at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen,   Data from three industry-sponsored clinical trials were analyzed for treatment outcomes in relation to location of the primary tumor. All studies were randomized: a first-line phase 3 (PRIME; NCT00364013), a first-line phase 2 (PEAK; NCT00819780) and a second-line phase 3 (181; NCT00339183) study. In order to have a biomarker refined patient population, only RAS/BRAF wild type (WT) cases were included. Information on tumor location (left/right colon) was obtained from the free-text surgery descriptions and from the original pathology reports. Primary tumors located in the caecum to transverse colon were coded as right-sided and tumors located from the splenic flexure to rectum were coded as left-sided. Tumor location ascertainment rate was greater than 80%. Between 80% and 85% of cases are left sided. Results for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) for each treatment were analyzed.
 
Patients with right-sided tumors did worse for all parameters compared to left sided. Panitumumab provided better outcomes than the comparator for tumors of left-sided origin.  See below comparison of left-sided versus right-sided Overall Survival (OS), Progression Free Survival (PFS) and Overall Response Rate:  
 
PRIME study (1st line):  
OS: Left:  32.5 mos versus Right: 22.5 mos. (p=0.17)
PFS: Left: 12.9 mos versus Right: 8.9 mos (p=0.01)
ORR:  Left: 70.3% versus Right: 52.0 %
 
PEAK study (1st line):  
OS: Left:  43.4 mos versus Right: 22.5 mos. (p=0.058)
PFS: Left: 14.6 mos versus Right: 10.3 mos (p=0.029)
ORR:  Left: 63.5% versus Right: 69.2 %
 
181 study (2nd line):  
OS: Left:  20.1 mos versus Right: 11.9 mos. (p=0.08)
PFS: Left: 8.0 mos versus Right: 6.8 mos (p=0.006)
ORR:  Left: 50.7% versus Right: 19.0 %
 
The result of these retrospective analyses on a homogenous RAS/BRAF WT subpopulation confirms that primary CRC arising on the right side is associated with poor prognosis regardless of treatment received. Moreover, panitumumab plus chemotherapy provide a benefit over chemotherapy with or without bevacizumab in left-sided tumors. No final conclusions can be drawn on the optimal treatment in patients with right-sided primary tumors.
 
2019 Update
A literature search conducted through June 2019 did not reveal any new information that would prompt a change in the coverage statement.
 
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2020. No new literature was identified that would prompt a change in the coverage statement.
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2021. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer.
 
A randomized, open-label, phase 3 clinical trial was conducted at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022).
 
The trial consisted of panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days.
 
The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate.
 
In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%).
Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population. (Watanabe J, Muro K, Shitara K, et.al., 2023)
CPT/HCPCS:
J9303Injection, panitumumab, 10 mg
References: Amgen Inc.;(2015) Vectibix® [package insert]. Thousand Oaks, CA: Amgen Inc.; 2015

Boeckx N, Toler A, et al.(2016) Primary tumor sidedness impacts on prognosis and treatment outcome: results from three randomized studies of panitumumab plus chemotherapy vs chemotherapy or chemotherapy plus bevacizumab in 1st and 2nd line RAS/BRAF WT mCRC; paper presented at European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen (Abstract #89P). https://cslide.ctimeetingtech.com/library/esmo/browse/itinerary/5286

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Blasinska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J.(2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860.

Elsevier.(2017) Panitumumab [Internet]. Tampa (FL): Elsevier. c2017- [cited 2017 April 13]. Available from: http://www.clinicalpharmacology.com

Gusti RM, Shastri KA, Cohen MH, Keegan P, Pazdur R on behalf of the Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration.(2007) FDA drug approval summary: panitumumab (Vectibix). Oncologist 2007 May; 12(5):577-583

National Comprehensive Cancer Network (NCCN).(2021) NCCN Drugs and Biologics Compendium. Panitumumab. NCCN.org/DrugCompendium. Accessed 9/2/2021.

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