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Beth benderfynodd Grŵp Asesu Meddyginiaethau Cymru’n Un?

Gellir rhoi panitumumab i drin canser metastatig colorefrol cam 4, math o ganser sy'n effeithio ar ochr chwith y coluddyn mawr (colon a rectwm) sydd wedi lledaenu i rannau eraill o'r corff, fel yr afu, yr ysgyfaint neu organau eraill. Dim ond os yw prawf gwaed yn dangos bod y canser yn debygol o ymateb i panitumumab y gellir rhoi panitumumab i drin y math hwn o ganser. Gellir rhoi panitumumab ar ôl 2 driniaeth flaenorol neu fwy gyda meddyginiaethau canser eraill. Mae'n rhaid bod y meddyginiaethau canser eraill hyn wedi cynnwys panitumumab neu feddyginiaeth debyg sy'n targedu proteinau penodol o'r enw EGFRs (derbynyddion ffactor twf epidermaidd) a geir ar bilenni celloedd canser.

Bydd panitumumab ar gael i gleifion cymwys sydd wedi cofrestru gyda phractis meddyg teulu yng Nghymru, hyd yn oed os oes angen iddynt dderbyn eu triniaeth y tu allan i Gymru.

Nid yw Panitumumab wedi'i drwyddedu i drin y math hwn o ganser metastatig y colon a'r rhefr, felly gelwir ei ddefnyddio yn y modd hwn yn ddefnydd “all-drwydded”. Pan gaiff meddyginiaeth ei defnyddio yn “all-drwydded”, rhaid i'ch meddyg esbonio'n glir i chi y risgiau a'r manteision o gymryd y feddyginiaeth. Dylai eich meddyg roi gwybodaeth glir i chi, siarad â chi am eich opsiynau a gwrando'n ofalus ar eich barn a'ch pryderon. Darllenwch ein taflen wybodaeth i gleifion am ddefnydd di-drwydded ac all-drwydded o feddyginiaethau.

Mae Grŵp Asesu Meddyginiaethau Cymru'n Un ac AWTTC yn adolygu'r penderfyniad hwn yn rheolaidd i weld a oes unrhyw dystiolaeth newydd a allai effeithio ar y penderfyniad hwn.

I gael rhagor o wybodaeth am ganser y colon a’r rhefr, ewch i: Bowel Cancer UK (Saesneg yn unig)

 

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What did the One Wales Medicines Assessment Group decide?

Panitumumab can be given to treat stage 4 metastatic colorectal cancer, a type of cancer affecting the left side of the large intestine (colon and rectum) that has spread to other parts of the body, such as the liver, lungs or other organs. Panitumumab can only be given to treat this type of cancer if a blood test shows that the cancer is likely to respond to panitumumab. Panitumumab may be given after 2 or more previous treatments with other cancer medicines. These other cancer medicines must have included panitumumab or a similar medicine that targets certain proteins called EGFRs (epidermal growth factor receptors) found on the membranes of cancer cells.

Panitumumab will be available to eligible patients who are registered with a GP practice in Wales, even if they need to receive their treatment outside Wales.

Panitumumab is not licensed to treat this type of metastatic colorectal cancer, so using it in this way is called “off-label” use. When a medicine is used “off-label”, your doctor must clearly explain to you the risks and benefits of taking the medicine. Your doctor should give you clear information, talk with you about your options and listen carefully to your views and concerns. Read our patient information leaflet about unlicensed and off-label use of medicines.

The One Wales Medicines Assessment Group and AWTTC review this decision regularly to see if there is any new evidence that may affect this decision.

For more information on colorectal cancer visit: Bowel Cancer UK

Medicine: panitumumab

Indication: Treatment of stage IV metastatic left-sided colorectal cancer with RAS wildtype confirmed by circulating tumour DNA following successful first line treatment with an epidermal growth factor inhibitor and at least one other treatment

Meeting date: 12 May 2025

Criterion: Clinical effectiveness and safety

OWMAG opinion OWMAG were presented with the Evidence Status Report (ESR) and noted the rationale for use of an epidermal growth factor inhibitor (EGFRi) as re-challenge treatment, guided by circulating tumour DNA analysis for RAS mutations, in stage IV metastatic colorectal cancer. OWMAG acknowledged that the AWMSG Scrutiny Panel had agreed that there was not sufficient evidence for the assessment of cetuximab for the same indication and that only panitumumab monotherapy was for consideration. The group noted the results presented from the CHRONOS study (a phase II multicentre, open label single arm trial), and the supporting evidence provided by two network meta analyses. The group acknowledged the low patient numbers in the CHRONOS trial (n = 27), the fact they were a heavily pre-treated population (a median of three prior therapies) and the lack of any direct comparative evidence. However, the 30% objective response rate (ORR) as highlighted by the clinical expert was noted. The clinical expert also highlighted the ORR (15.1%) for trifluridine-tipiracil (Lonsurf) plus bevacizumab in vascular endothelial growth factor (VEGF) naïve patients (as UK patients would be) which is the reason clinicians favour this particular treatment as the optimal third line therapy. The group also noted the favourable ORR reported for panitumumab rechallenge in CHRONOS compared to regorafenib in the CONCUR and CORRECT trials as highlighted by the clinical expert. The group acknowledged the poor adverse effect profile of regorafenib when compared with panitumumab. The clinical expert explained that panitumumab would mainly be used in patients who had received third line trifluridine-tipiracil (Lonsurf) plus bevacizumab. Current fourth line treatment options are regorafenib or best supportive care. Panitumumab would be expected to replace regorafenib at fourth line due to the higher ORR reported in CHRONOS and the more favourable adverse effect profile. The group acknowledged that indirect treatment comparisons between panitumumab as rechallenge and current treatment options was not possible due to the heterogeneity between study designs and patient characteristics, in particular with respect to the number of previous treatments patients had received. OWMAG accept that panitumumab re-challenge is most likely to be used in the fourth line setting and reserved as a third line option for those patients who are unable to tolerate or are unsuitable for trifluridine-tipiracil plus bevacizumab treatment. OWMAG considered that the evidence provided in the CHRONOS study and supporting network meta-analyses demonstrated a clear clinical benefit for panitumumab as an EGFRi re-challenge for patients with stage IV metastatic left-sided colorectal cancer with RAS wild type confirmed by circulating DNA.

Criterion: Cost-effectiveness

OWMAG opinion There is no published cost effectiveness evidence available for panitumumab in this indication. Therefore OWMAG considered the cost consequence analysis, scenario analysis and threshold analysis presented in the ESR. The group acknowledged the limitations of the analyses in terms of capturing all costs and effects. The group noted the cost consequence analyses for each potential line of therapy (third, fourth or fifth) and acknowledged that whilst the most likely place in therapy would be as a fourth line option the most plausible analyses would be the fourth and the fifth line scenarios, as regorafenib might not necessarily be used by all clinicians in Wales. The group considered that a 1.7 severity modifier was reasonable to apply for the indication. The group concluded that due to the range of conservative assumptions, particularly surrounding the relative quality of life (QoL) and modelling of QoL, that panitumumab was plausibly cost-effective in the 3rd, 4th, and 5th line of therapy.

Criterion: Budget impact

OWMAG opinion OWMAG considers the estimated patient numbers provided by the clinical expert to be reasonable whilst accepting that in year one numbers may be lower than anticipated and will increase to the estimate in about three years. The group also noted the clinical expert estimate that numbers may rise again in five to six years’ time due to increased mCRC diagnoses. OWMAG considers the additional cost of the circulating tumour DNA testing to be reasonable. The group note that the clinical expert and AWTTC team have been in communication with the All Wales Medical Genomics Service (AWMGS) who confirm that they have capacity to accommodate the additional tests without any adverse effect on the usual 5-day turnaround time. The group considers the use of the median PFS from treatment duration from the CHRONOS and SUNLIGHT trials to provide reasonable estimates for treatment duration on panitumumab and trifluridine-tipiracil plus bevacizumab. The uncertainty as to how many patients would be treated at each line of therapy was acknowledged and it was noted that the number of patients receiving panitumumab at the later lines of therapy are likely to be lower than those presented. Whilst acknowledging the absence of costs for monitoring and treating adverse events OWMAG consider the data presented to be a plausible estimate of the expected budget impact at each line of treatment. The group consider that the most likely place in therapy to be fourth line. OWMAG acknowledge that there will be some patients treated at third and fifth line. OWMAG consider panitumumab to be a reasonable use of NHS resources.

Criterion: Resource use

OWMAG opinion OWMAG note the additional resource required for ctDNA testing and consider it to be reasonable. Additional resource for IV infusion compared to oral preparations at fourth line were acknowledged.

Criterion: Other factors

OWMAG opinion OWMAG note that patients with stage IV colorectal cancer who have already received two treatments, whilst typically being relatively fit, have a limited life expectancy. Panitumumab may have the potential to extend the overall survival of patients by several months or more. The treatment may also improve the quality of life or maintain quality of life for both the patient and their family/carer. The group also noted the increase in diagnoses in younger people. The group recognised the benefit of regular treatment sessions for some patients as highlighted by the clinical expert. OWMAG acknowledge that panitumumab is administered by IV infusion in hospital and the comparator regorafenib is administered orally. Patients who live a distance from hospitals may not want to travel.

Final recommendation

OWMAG recommends the use of panitumumab for treatment of stage IV metastatic left-sided colorectal cancer with RAS wildtype confirmed by circulating tumour DNA following successful first line treatment with an epidermal growth factor inhibitor and at least one other treatment.

Summary of rationale

OWMAG recognise that whilst the evidence base is limited, and of low quality, panitumumab offers a targeted treatment option for this specific group of patients with stage IV colorectal cancer and is likely to extend overall survival compared to other treatment options. The group consider the cost consequence analysis and budget impact data presented to demonstrate a reasonable use of NHS resources.

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Key findings

Licence status: Panitumumab (Vectibix^®) is not licensed for treatment of stage IV metastatic left-sided colorectal cancer with RAS (rat sarcoma virus) wild-type confirmed by circulating tumour DNA (ctDNA) following successful first line treatment with an epidermal growth factor inhibitor (EGFRi) (either cetuximab or panitumumab) and at least one other treatment; its use for this indication is off-label.

Clinical evidence: The clinical evidence for the use of panitumumab in this setting comes from a phase II multicentre, open-label, single-arm clinical trial. A total of 36 patients were eligible for panitumumab rechallenge, 27 received treatment per protocol. The trial reported a 30% objective response rate with 8 partial responses, and a median duration of response of 17 weeks. An additional 40% of patients had stable disease, with 82% maintaining it for over 4 months. The disease control rate was 63%, and the median progression-free survival was 16 weeks, while median overall survival was 55 weeks.

Safety: The safety of panitumumab was found to be in line with previous literature; no new safety signals emerged with rechallenge of panitumumab in colorectal cancer compared with its use in other indications.

Patient factors: Panitumumab rechallenge can control tumours without the need for chemotherapy. It targets EGFR in tumours sensitive to this therapy, offering the possibility of renewed responses in patients who previously benefited from panitumumab. Panitumumab is administered through an intra-venous (IV) infusion, as is the preferred third line treatment option of oral trifluridine-tipiracil (Lonsurf^®) plus IV bevacizumab. Current fourth line treatment options (regorafenib or trifluridine-tipiracil [Lonsurf^®]) are both oral preparations.

Cost effectiveness: An All Wales Therapeutics and Toxicology Centre (AWTTC) literature review did not identify any published studies reporting the cost-effectiveness of panitumumab in the 3rd or later line in the treatment of stage IV metastatic left-sided colorectal cancer with RAS wildtype.

An AWTTC cost consequence analysis (CCA) compares the costs and outcomes of panitumumab with a range of comparators, according to line of treatment, in the treatment of stage IV metastatic left-sided colorectal cancer with RAS wildtype.

Base case analysis, treatment in the third line, suggests that panitumumab is associated with lower costs and higher overall survival. Scenario analysis finds that panitumumab costs more than the fourth-line (regorafenib) and fifth-line best supportive care (BSC) comparators whilst offering increased overall survival. The cost analysis is limited in scope, as it does not consider full resource costs or the costs of adverse events. It is considered possible that the inclusion of these costs could change the costing conclusion.

A threshold analysis found the quality adjusted life years (QALYs) required range between [commercial in confidence text removed], this is dependent on the willingness-to-pay threshold and treatment line.

Budget impact: For an estimated 30–50 patients eligible for treatment panitumumab is expected to be cost saving as a third line treatment. [commercial in confidence text removed] The budget impact is subject to considerable uncertainty.

Impact on health and social care services: Genomic testing is not routinely available for this indication and may have an impact on laboratory services. Regorafenib is an oral treatment, whereas panitumumab requires bi-weekly intravenous administration until treatment progression or the development of intolerable side effects. However, the overall impact from the administration difference is likely minimal due to the relatively small patient numbers.

Innovation and/or advantages: Clinical experts indicate the main benefit of this treatment is its survival advantage over existing options, whist also providing a chemotherapy-free regimen which may be better tolerated than current treatment options.

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Background

Most patients with metastatic colorectal cancer (mCRC) have incurable, unresectable disease. Treatment aims to slow tumour progression, manage symptoms, improve survival, preserve quality of life, and reduce treatment side effects.

Clinicians in Wales have identified a cohort who would benefit from panitumumab re-challenge, providing a survival advantage (compared to current treatment options) and offering a chemotherapy-free regimen. Panitumumab was therefore considered suitable for assessment though the One Wales Medicines process.

[confidential information removed]

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Target group

The indication under consideration is stage IV metastatic left-sided colorectal cancer with RAS (rat sarcoma virus) wild-type confirmed by circulating tumour DNA (ctDNA) following successful first line treatment with an epidermal growth factor inhibitor (EGFRi) and at least one other treatment.

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Marketing authorisation date

Not applicable, off-label. 

Panitumumab (Vectibix^®) is not licensed for the target group.

Panitumumab (Vectibix^®) is indicated for the treatment of adult patients with wild-type RAS mCRC¹:

• in first line in combination with folinic acid, fluorouracil and oxaliplatin (FOLFOX) or folinic acid, fluorouracil and irinotecan (FOLFIRI)
• in second line in combination with FOLFIRI for patients who have received first line fluoropyrimidine-based chemotherapy (excluding irinotecan)
• as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

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Dosing information

The licensed dose as monotherapy for colorectal cancer is 6mg/kg administered by IV infusion every two weeks¹. 6mg/kg is also used for re-challenge in the pivotal CHRONOS clinical trial². Treatment is continued until treatment progression or the development of intolerable side effects.

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Clinical background

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Incidence/prevalence

Colon cancer makes up 72% of colorectal cancer cases, while rectal cancer accounts for 28%¹³. In the UK, around 44,000 new cases are diagnosed annually, representing 12% of all cancers¹⁴, with 666 Stage IV cases in Wales in 2021¹⁵. Stage IV mCRC has a poor prognosis, with 1-year survival rates of about 44% and 5-year survival rates under 10%¹⁶.

Clinicians consulted by the (AWTTC estimate that there are around 200-250 metastatic patients each year, with 60% having left-sided tumours and 50% of those being RAS wild-type. Approximately 50‑80 patients annually will undergo ctDNA testing, with 60% of them being eligible for rechallenge. This results in an estimated 30 to 50 patients per year in Wales who would qualify for treatment with an EGFRi.

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Current treatment options and relevant guidance

Patients with mCRC have disease that is incurable; treatment goals are focused on delaying tumour progression, alleviating tumour-related symptoms, optimising survival, preserving quality of life (QoL), and minimising treatment-related toxicity¹⁶.

First-line treatment involves targeted biologic therapy tailored to the mutation profile and tumour location, such as cetuximab or panitumumab combined with chemotherapy (FOLFOX or FOLFIRI) for left-sided RAS wild-type tumours¹⁷. Second-line treatment usually involves chemotherapy, with the specific regimen chosen based on the patient's first line therapy¹⁸. The proposed treatment under consideration would be third line or later with the current treatment pathway based on Welsh clinical expert clinical advice and current NICE TA-approved treatments.

Third line treatment for RAS wild-type mCRC

In the third line setting, after progression following second line treatment, patients with RAS wild-type mCRC are often treated with targeted therapies. Key options include:

• Trifluridine-tipiracil (Lonsurf^®) (administered orally) with IV bevacizumab is licensed and NICE approved after the failure of two lines of treatment¹⁶
• Trifluridine-tipiracil (Lonsurf^®) alone is NICE approved at this line of treatment¹⁹
• Regorafenib (administered orally) is similarly NICE approved¹⁹

Fourth line treatment for RAS wild-type mCRC

In the fourth line setting, treatment options are more limited, but there are still effective therapies:

• Regorafenib: In accordance with NICE TA866¹⁶, regorafenib can continue to be an option in the fourth line setting for patients who have failed earlier treatments and have not received regorafenib.
• Trifluridine-tipiracil (Lonsurf^®):  if trifluridine-tipiracil was not used in the third line setting, it can still be considered in the fourth line setting for patients with progressive disease, in accordance with NICE TA405²⁰. However, clinical expert opinion is that in practice patients will have been treated with trifluridine-tipiracil (Lonsurf^®) plus bevacizumab at third line therefore regorafenib would be the treatment of choice.
• Best Supportive Care (BSC): In cases where all available treatments have been exhausted and the patient has a poor performance status, the focus may shift toward BSC, which aims to improve the patient's quality of life.

Panitumumab monotherapy for mCRC that has progressed after first line chemotherapy was appraised by NICE in 2012. At the time NICE decided not to recommend panitumumab in this setting stating that it did not provide enough benefit to patients to justify its high cost even when the special considerations were applied²¹. However, the marketing authorisation holder has informed AWTTC that rechallenge falls outside the marketing authorisation for this medicine and therefore this NICE recommendation would not apply as NICE advice does not include off-label use of a medicine.

Fruquintinib for previously treated mCRC is currently undergoing NICE TA, publication date is to be confirmed at the time of writing this report²².

The European Society for Medical Oncology (ESMO) has recently updated its treatment guidelines for unresectable mCRC in the third-line setting and beyond⁶. For patients with RAS wild-type, ESMO recommends several third-line and later treatment options, including trifluridine-_­tipiracil with or without bevacizumab, panitumumab, irinotecan with cetuximab and regorafenib.

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Summary of evidence on clinical effectiveness

A literature search was conducted in February 2025 by the All Wales Therapeutics and Toxicology Centre (AWTTC) relating to panitumumab as rechallenge monotherapy in metastatic colorectal cancer with RAS wild-type identified on circulating tumour DNA testing. Searches were performed using Cochrane, Central Register of Controlled Trials, EMBASE, MEDLINE and TRIP database. The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), adverse events (AE), health related quality of life (HRQoL) and resource use. A literature search identified 268 records which were assessed for eligibility, with 80 excluded following removal of duplicates and screening of title and abstracts. Following eligibility screening, three publications were included in the report covering one clinical trial, and two meta-analyses and systematic reviews. The remaining records were excluded due to small patient numbers, incorrect cohort or unsuitable study design (see Appendix 1 - image opens in new window). The company also provided information that contributed to the development of the findings in this report.

Efficacy

Safety

Discussion

Panitumumab is licensed as monotherapy for later treatment of mCRC, although to be included in the two randomised controlled trials (RCTs) on which the licence is based, participants must have been naïve to prior treatment with panitumumab. The first was a Phase III trial comparing panitumumab monotherapy with BSC versus BSC alone in 463 patients with chemorefractory, wild-type KRAS mCRC, who had a median of two prior treatments²⁵. Panitumumab showed significant benefits over BSC, improving OS (10.0 vs. 7.4 months), PFS (3.7 vs.1.9 months), and achieving a 10% response rate²⁵. The second Phase III, randomised, open label, non-inferiority trial compared panitumumab with cetuximab in 1,010 patients with wild-type KRAS mCRC, also with a median of two prior treatments²⁶. The results showed no significant difference in OS (10.0 vs. 9.9 months) or PFS (3.7 months for both treatments), with comparable response rates²⁶. Overall these studies demonstrate a similar response rate to CHRONOS, however the main difference being that CHRONOS patients were not naïve to EGFRi treatment and the CHRONOS trial aimed to improve patient selection using molecular profiling through ctDNA, targeting those less likely to have developed resistance mutations, potentially leading to better outcomes.

CHRONOS was a phase II multicentre, open-label, single-arm clinical trial². All patients had received an EGFRi plus chemotherapy (as per UK clinical practice) and prior treatments received were relevant to those used in UK clinical practice. Patients had received a median of three prior treatments, almost all patients had an eastern cooperative oncology group (ECOG) status of 0 or 1 and most patients had left-sided disease (63%) which is most likely to reflect the population eligible for this treatment. However, the study lacked a formal comparison between retreatment with anti-EGFR therapy and standard later line treatments. The trial also lacked long-term follow-up, preventing assessment of treatment durability and safety².

Over the last ten years there have been a number of medicines approved for third-line or later treatment of mCRC (see current treatment section above) which have improved survival rates in this clinical setting. The median OS for third-line treatment with trifluridine-tipiracil plus bevacizumab was 10.8 months in the SUNLIGHT study with a PFS of 5.6 months²⁷. Regorafenib has been studied in two main clinical trials: CONCUR and CORRECT^28,29. In CONCUR, OS was 8.8 months²⁸. In CORRECT, participants were heavily pre-treated, with approximately 50% having received four or more lines of prior treatment, which may have in part accounted for the lower OS of 6.4 months²⁹. RAS wild-type status was not tested in either of the regorafenib trials.

CONCUR and CORRECT were both placebo-controlled trials with a control arm of best supportive care alone. Overall survival in the control groups were 6.3 and 5 months respectively^28,29.

In their submission to NICE (TA1008, published September 2024)¹⁹, the manufacturers of trifluridine-tipiracil conducted a network meta-analysis (NMA) to provide an indirect comparison of the relative treatment effectiveness for OS and PFS of trifluridine-tipiracil plus bevacizumab with regorafenib. The NMA results favoured trifluridine-tipiracil plus bevacizumab over regorafenib for both OS (Hazard ratio [HR] 0.60, 95% CI 0.38 to 0.95) and PFS (HR 0.49, 95% CI 0.31 to 0.84)¹⁹. For NICE TA866¹⁶, the company reported similar efficacy between regorafenib and trifluridine-tipiracil based on a fixed-effect network meta-analysis model, with an OS HR of 0.99 (95% CI 0.84 to 1.17)¹⁶. Although the NICE commented on the heterogeneity between trials, the Committee concluded that regorafenib was likely to provide similar benefits in terms of PFS and OS to trifluridine-tipiracil.

It is difficult to draw any firm conclusions or undertake an indirect analysis between panitumumab and the relevant comparators due to heterogeneity between studies in terms of number and type of prior treatments, differences in study design and characteristics of study participants. Many of the comparator studies also did not test RAS status or RAS status was known for only a proportion (30.7% of patients in SUNLIGHT had RAS wild-type disease²⁷) of the study population.

The conclusions of two meta-analyses by de Moraes et al (2024) and da Silva et al (2024) are supportive of the findings of the CHRONOS trial, as well as the use of ctDNA as a guide for treatment^23,24 They are however limited by the heterogenous nature of the studies included and the fact that most participants received combination treatment. This could potentially limit the generalisability of the results to patients receiving panitumumab as a single-agent therapy.

The biological rationale behind rechallenging is not entirely understood, and clinical data supporting efficacy of panitumumab rechallenge are still lacking. While some studies have shown that rechallenge can be beneficial for certain patients², long-term outcomes remain uncertain.

Panitumumab is commonly associated with skin reactions, including acneiform rash, dry skin, pruritus, and paronychia, affecting up to 90% of patients¹. Other commonly reported adverse events include fatigue, diarrhoea, and infusion-related reactions. While dose adjustments or interruptions can help manage side effects, they may reduce the drug's effectiveness. Overall, the available information suggests that panitumumab safety is consistent with the profile known for its pharmacological class and no new signals have been identified¹. Data available, although limited in size and long-term exposure, appear acceptable and suggest a tolerable profile.

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Cost-effectiveness evidence

A literature review conducted by AWTTC did not identify any studies relevant to the cost-effectiveness of panitumumab in third-line or later-line treatment of stage IV metastatic left-sided colorectal cancer with RAS wildtype. The lack of cost-effectiveness evidence for the indication is not unexpected given the paucity of clinical trial data for panitumumab in third-line or later-line treatment of stage IV metastatic left-sided colorectal cancer with RAS wildtype.

An AWTTC cost consequence analysis (CCA) compares selected resource use and clinical outcomes associated with panitumumab (6mg/kg once every two weeks) with a range of comparators in the treatment of stage IV metastatic left-sided colorectal cancer with RAS wildtype. The analysis adopts a lifetime horizon and an NHS Wales/Personal and Social Services perspective. Costs are discounted at 3.5% per annum.

Cost of intervention

The administration of panitumumab is displayed in Table 1, the per cycle dose of 6 mg/kg every two weeks is informed by the SmPC. The average weight of the patient cohort is calculated at 79.7 kg, this equates a cycle dose of 478 mg. An 8-cycle administration is used for the per person panitumumab cost, this aligns with the 17-week median progression free survival from the CHRONOS study².

Resource use following treatment is described as BSC, cost inputs for this were identified from the literature. An AWTTC targeted literature search was undertaken to identify published figures reporting resource use and costs associated with BSC for patients with mCRC. One applicable estimate was identified within NICE Evidence Review Group report for TA405²⁰, inflated to £260 in 2025 (supplementary Table 1.a). The drug acquisition cost is based on patient access scheme (PAS) price and does not include VAT. For the lifetime horizon the duration of BSC is calculated as the OS minus PFS reported in the CHRONOS study, the total intervention cost of panitumumab is [commercial in confidence text removed].

Table 1. Panitumumab: diagnostic, procurement, and administration costs (opens image in new tab)

Cost of comparators

The analysis includes the costs considerations for the third-line, fourth-line, and fifth‑line treatments reflecting the current use within the NHS in Wales as informed by clinical experts. Patients are modelled to receive treatment with either panitumumab or the appropriate comparator according to the line of treatment. Table 2 reports the range of comparators and the total per patient cost. The comparator for third-line therapy is trifluridine-tipiracil plus bevacizumab; fourth-line is regorafenib; and fifth-line is BSC. BSC costs are applied to each line of treatment following the median treatment duration up until death. The cost of comparators and the relative cost compared to panitumumab is reported in Table 2. Treatment durations have been based on OS data from SUNLIGHT, CORRECT and CONCUR clinical trials (Table 3)^27-29. Cost details for the range of comparators is offered in Appendix 2a and Appendices 2b and 2c (opens images in new tab).

Table 2. Comparator costs (opens image in new tab)  

Clinical outcomes

The clinical outcomes and health-related quality of life effects captured in the cost-consequence analysis are informed by the literature where possible, and by clinical expert opinion where published evidence is lacking. The summary of evidence on clinical effectiveness section provides greater detail on the sources of the primary and secondary clinical outcomes included, and the rationale for apportioning applicability to the targeted population. The key clinical outcomes, progression free survival, overall survival, and treatment emergent adverse events of grade three or higher are reported according to treatment line are reported in Table 3. Clinical experts have reported that the distribution of patients for this indication within the Welsh NHS is likely to be 56% third-line, 31% fourth-line and 13% fifth-line (supplementary Table 1.d).

Table 3. Progression free survival, overall survival and adverse events (opens image in new tab)

Results

In the base case analysis panitumumab was found to cost [commercial in confidence text removed] less than trifluridine-tipiracil plus bevacizumab in the third line of therapy and is associated with higher overall survival and reduction of adverse events (Table 4); progression-free survival, however, was shorter.

Table 4. Base case analysis (opens image in new tab)

Scenario analyses

Clinical experts have reported that approximately 44% of patients treated would be in later lines (fourth and fifth). Comparison of panitumumab to regorafenib as a fourth-line therapy and best supportive care as a fifth-line approach is detailed in Table 5. Panitumumab was found to be more costly than both the fourth-line and fifth-line options whilst offering improved overall survival. Progression free survival was higher in the panitumumab group with a lower adverse event rate compared with regorafenib.

Table 5. Fourth-line and Fifth-line cost consequence analyses (opens image in new tab)

Threshold analyses

To characterise the scale of the differences in costs and overall survival a range of threshold analyses are undertaken at the willingness-to-pay values of £20,000 and £30,000 per quality adjusted life year (QALY). In the base case analysis panitumumab costs less and increases survival. Table 6 reports the threshold QALYs required, and the potential average health-related quality of life (HRQoL) required, over the additional overall survival, for the two alternative scenarios. The required HRQoL average for panitumumab to reach the £20,000 threshold is highest [commercial in confidence figure removed] when compared to the fifth-line option of BSC, this is due to the high net cost.

Table 6. Threshold analysis (opens image in new tab)

To inform and contextualise the threshold analysis an AWTTC targeted literature review sought disease specific HRQoL for patients with stage IV left-sided mCRC cancer with RAS wildtype, Odom et al. (2011) was chosen due to the closeness of patient match and study size³². Odom et al. report a baseline weighted HRQoL figure of 0.71. Clinical experts have reported that HRQoL is expected to reduce in a linear trend across the overall survival duration. Applying the overall survival durations with the baseline HRQoL of 0.71, calculations offered in supplementary Table 1.e, that declines linearly results in area under the curve QALYs which are reported in Table 7.

Table 7. Potential QALY by treatment line (opens image in new tab)

Cost-effectiveness evidence limitations

• There are no published cost-effectiveness studies for this intervention.
• The analysis adopts a limited cost approach which doesn’t consider the cost of adverse events and ongoing resource use. It is unknown what impact this has on the analysis aside from an increase in uncertainty.
• The clinical inputs from the CHRONOS trial are not specific to one line of therapy. Whilst the range of lines within this analysis (third, fourth and fifth) are observed within the trial, the lack of line specific overall survival, progression free survival and adverse event rate reduces the robustness of the analysis. A negative relationship between OS and lines of therapy may result in underestimating relative overall survival in earlier lines of therapy whilst overestimating relative overall survival in later lines.
• The comparative clinical effectiveness trials are not restricted to administration in single lines of therapy. Evidence sourced from trials where treatment is delivered in a range of lines of therapy may induce bias. 
• The patient characteristics of the CHRONOS trial vary from the comparator evidence trials. Patients in latter lines of therapy may achieve worse health outcomes, the single estimate for panitumumab lacks this detail.
• The evidence used to inform line specific clinical outcomes for the comparators is sourced from trials which include patients with a range of prior lines of therapy. This lack of patient/line matching may induce bias to the analysis in cases where there is a correlation between prior lines of therapy and clinical outcomes.
• The mapping of QoL over time is informed by experts, the simplistic linear slope may underestimate the benefits of extensions to progression-free and overall survival.
• The comparator clinical evidence is sourced from separate studies to that of the intervention, the lack of directly comparative evidence limits the certainty of the findings.
• The simple approaches used in this analysis may lack the accuracy and nuance of a full partitioned survival model, however, the clinical evidence was insufficiently detailed to undertake such analysis.
• The targeted literature searches used to identify resource use and utility data are inferior to undertaking full systematic reviews for these inputs, the confidence and robustness of the conclusions are subsequently limited.

Table 8. Examples of medicine acquisition costs (opens image in new tab)

Table 9. Severity modifier considerations for One Wales Medicines Assessment Group (OWMAG) (opens image in new tab)

If OWMAG conclude that panitumumab should be considered under the AWMSG policy for appraising medicines for severe conditions, OWMAG will need to consider:

• the effect of the severity QALY weight applied, and whether the weighted QALY benefits in this patient group result in a most plausible ICER that falls within the current cost-effectiveness threshold range.

In addition, OWMAG will need to be satisfied that:

• The estimates of the expected life years and total QALYs for the general population and for patients being treated with the comparator medicines(s) are sourced from recent and robust data sources.
• The assumptions used in the economic modelling are plausible, objective and robust.

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Budget impact

The Patient Access Scheme (PAS) price of panitumumab (Vectibix^®) is [commercial in confidence text removed]. Clinical experts estimate that patients will receive a maximum of 6 months treatment (12 cycles).

Medicine acquisition costs for panitumumab and comparators for one month of treatment are provided in Table 10. NHS Wales secondary care prescribing figures from 2024 for bevacizumab have been used to calculate a weighted average procurement cost (supplementary Table 1.b).

Table 10. Cost of panitumumab and comparators in Wales (per patient) (opens image in new tab)

Associated resource costs for panitumumab and comparators are defined in Table 1. Clinical experts estimate that 50 to 80 patients per year would be suitable for ctDNA testing and 60% of them would be identified as RAS wild-type and be eligible for treatment with panitumumab as re-challenge (30 to 50 patients in Wales). Resource costs for these lower and upper estimates are provided in Table 11.

Table 11. Net resource costs for upper and lower patient number estimates for panitumumab and comparator treatments (opens image in new tab)

Clinical expert opinion is that the current available preferred treatment option at third line would be for trifluridine-tipiracil (Lonsurf^®) with bevacizumab. For patients not fit enough to receive bevacizumab, trifluridine-tipiracil (Lonsurf^®) alone is an option for use. At fourth line regorafenib or BSC are the current treatment options and fifth line and beyond is BSC. Median progression free survival for patients receiving panitumumab in the CHRONOS study and treatment duration for trifluridine/tipiracil with bevacizumab in the SUNLIGHT trial and for regorafenib in the CONCUR and CORRECT trials have been used to inform the treatment duration for the panitumumab and comparators for the budget impact calculations shown in Tables 12 and 13^2,27-29. It is assumed that patients progressing on active treatment would go on to receive BSC therefore where the duration of treatment is less than 4 months, the remainder of the treatment would be BSC.

The budget impact for panitumumab versus trifluridine-tipiracil (Lonsurf^®) with bevacizumab as third line treatment is detailed in Table 12. In this setting panitumumab is overall cost saving based on medicine acquisition cost alone. The table shows costs for the lower and upper estimates of patient numbers for 4 months of treatment, as per the progression free survival in the CHRONOS trial². Table 13 details the budget impact for panitumumab used as a fourth line treatment versus regorafenib or best supportive care. If panitumumab is used as fifth line treatment or above the comparator treatment is BSC, which is predominately primary healthcare resource cost with no significant medicine acquisition costs. From fifth-line onwards the budget impact will equal the acquisition cost of panitumumab, [commercial in confidence text removed].

Table 12. Budget impact for four months panitumumab as third line treatment (opens image in new tab)

Table 13. Budget impact for four months panitumumab as fourth line treatment (opens image in new tab)

Budget impact discussion

• The budget impact shows that panitumumab re-challenge is likely to be cost saving as a third line treatment for this small sub-group of patients. This assumes the current favoured option for third line treatment is trifluridine/tipiracil plus bevacizumab. [commercial in confidence text removed].
• There is considerable uncertainty as to the number of patients treated at each line respectively. In the CHRONOS study the median number of previous treatments was three, in SUNLINGHT the majority of patients (93%) had received two prior treatments^2,27. In CONCUR and CORRECT the majority of patients had received three or more previous treatments^28,29. If these studies reflect real world practice then fourth- and fifth-line budget impact estimates are likely to be more plausible. However, if this were the case then patient numbers may be expected to be towards the lower end of the estimate due to the poor overall survival of this patient group.
• The duration of treatment is subject to significant uncertainty. CHRONOS did not report a median treatment duration, PFS was used as a proxy so may be an over estimate². Median treatment duration from study results were used for the comparator medicines. The results of the studies used to estimate treatment duration were not stratified by the number of previous treatments. It would be reasonable to assume that treatment duration would be longer for those patients who had received fewer treatments.
• The weighted average procurement cost for bevacizumab may fall slightly if biosimilar uptake increases in Wales. This is unlikely to affect future budget impacts significantly as the bevacizumab acquisition cost is not the main driver for the total cost for trifluridine/tipiracil plus bevacizumab.
• Monitoring costs are not included, clinical experts state that monitoring is the same for panitumumab as for comparator treatments.
• Treatment of adverse event costs have not been included however are expected to be similar for each treatment arm and small in comparison to drug acquisition costs^19,21.
• Administration costs are higher for subsequent treatment cycles than for the initial administration costs for bevacizumab and panitumumab. The NHS cost code SB15Z for delivery of subsequent chemotherapy covers a range of subsequent chemotherapy regimens from simple to highly complex⁴¹. It is therefore likely to be an overestimation of the costs for these more simple, single agent regimens with short infusion times after the first dose (30 to 60 minutes)^1,39.
• The resource costs associated with BSC is subject to significant uncertainty. There are very limited data available for BSC in mCRC which would be classed as palliative care for this indication. Gardiner et al (2018) performed a systematic review to explore activity and unit cost data for palliative care and concluded that due to limited data and heterogeneity it was not possible to provide an aggregate cost of palliative care in the UK⁴². We report costs provided for the appraisal of NICE TA405, trifluridine-tipiracil for previously treated mCRC inflated to 2025 prices. The costs comprise primary care costs only so may be someway reflective of BSC for comparison to active treatment with patients receiving support at home rather than in a hospice or as a hospital in-patient.

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Equality and health impact assessment

AWTTC have completed an Equality and Health Impact Assessment in parallel with each development stage of the project. This follows the five ways of working for public bodies, and work to achieving the wellbeing goals, outlined in the Well‑Being of Future Generations (Wales) Act 2015.

It is not expected that panitumumab will have significant potential negative impact on people based on the protected characteristics of the Equality Act 2010.

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Additional factors

Prescribing unlicensed medicines

Panitumumab (Vectibix^®) is not licensed to treat this indication and is therefore prescribed ‘off label’. Prescribers should consult their relevant guidelines on prescribing unlicensed medicines before any off-label medicines are prescribed.

Care has been taken to ensure the information is accurate and complete at the time of publication. However, the All Wales Therapeutics and Toxicology Centre (AWTTC) do not make any guarantees to that effect. The information in this document is subject to review and may be updated or withdrawn at any time. AWTTC accept no liability in association with the use of its content. An Equality and Health Impact Assessment (EHIA) has been completed in relation to the medicine and has been published on the AWTTC website.

Information presented in this document can be reproduced using the following citation: All Wales Therapeutics & Toxicology Centre. Evidence Status Report. RPanitumumab (Vectibix^®) for treatment of stage IV metastatic left-sided colorectal cancer with RAS wildtype confirmed by circulating tumour DNA following successful first line treatment with an epidermal growth factor inhibitor and at least one other treatment. Reference number: OW29. 2025.
Copyright AWTTC 2025. All rights reserved.

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• Original assessment: OWMAG recommendation with starting and stopping criteria June 2025 PDF 112KB
• Original assessment: OWMAG decision rationale June 2025 PDF 30KB
• Original assessment: Evidence Status Report June 2025 PDF 242KB
• Original assessment: Supplementary data tables June 2025 PDF 54KB
• Original assessment: Equality and Health Impact Assessment June 2025 PDF 185KB