The pan-Canadian Oncology Drug Review committee (pCODR) gave Bristol-Myers Squibb's (BMS) Erbitux a negative recommendation, while Roche's (Switzerland) Kadcyla and Erivedge were recommended for funding conditional on the improvement of their cost-effectiveness.
IHS Global Insight perspective | |
Significance | The pCODR's Expert Review Committee (pERC) did not recommend funding for BMS's Erbitux, while Roche's Kadcyla and Erivedge both secured favourable recommendations conditional on the improvement of their cost-effectiveness. |
Implications | The unfavourable recommendation for Erbitux is a setback for BMS, however results from an ongoing study (CALGB-C80405) comparing Kadcyla with Avastin as a first-line treatment for K-RAS wild-type unresectable metastatic colorectal carcinoma (mCRC) could aid BMS in a resubmission application. |
Outlook | Kadcyla and Erivedge received more favourable recommendations from the pERC, however Roche will likely be under pressure as individual jurisdictions aim to negotiate lower prices to improve the cost-effectiveness of the drug. |
The pan-Canadian Oncology Drug Review (pCODR) Expert Review Committee (pERC) has issued a final decision regarding funding for Bristol-Myers Squibb's (BMS; US) Erbitux (cetuximab), and Roche's (Switzerland) Kadcyla (trastuzumab emtansine) and Erivedge (vismodegib).
BMS's Erbitux
The pERC did not recommend funding for BMS's Erbitux as a first-line treatment for EGFR-expressing K-RAS wild-type metastatic colorectal carcinoma (mCRC) in combination with FOLFIRI (irinotecan, 5-flourouracil, leucovorin) due to uncertainty of the drug's benefit over bevacizumab and FOLFIRI as well as its lack of cost-effectiveness compared to this standard of care treatment. While the committee noted the need for a treatment option for patients with a contraindication to bevacizumab, the cost-effectiveness of cetuximab and FOLFIRI compared to FOLFIRI alone is unknown.
Clinical results assessed in the study included the CRYSTAL comparing cetuximab and FOLFIRI with FOLFIRI alone, which reported statistically significant improvements in overall survival (OS) and progression-free survival (PFS). The pERC also looked at the FIRE-3 study, comparing cetuximab and FOLFIRI with bevacizumab and FOLFIRI, the current standard of care for this indication, however discordant results were reported between OS and PFS.
At Erbitux's list price, CAD367.75 (USD337.54) per 100 mg vial, the average cost of treatment is CAD256.77 per day or CAD7,189.51 over a 28-day course of treatment. The recommended dose drops subsequent to initial treatment to CAD6,251.75 for a 28-day course. Bevacizumab, on the other hand, costs CAD125 per 5 mg, and the average cost of treatment is CAD125 per day, or CAD3,500 per 28-day course. FOLFIRI costs an estimated CAD402.56 per 28 days of treatment. Therefore, cetuximab and FOLFIRI was not considered cost-effective compared to bevacizumab and FOLFIRI.
The committee has highlighted the need for results from an ongoing study (CALGB-C80405) comparing cetuximab with bevacizumab as a first-line treatment for K-RAS wild-type unresectable mCRC, which could aid BMS in a resubmission application, along with cost-effectiveness analysis for cetuximab plus FOLFIRI versus FOLFIRI alone in patients with a contraindication to bevacizumab. The full reimbursement decision can be found here.
Roche's Kadcyla
The pERC has recommended the funding of Roche's Kadcyla as a treatment for patients with HER2-positive, unresectable locally advanced or metastatic breast cancer in patients that have already received treatment with trastuzumab and chemotherapy, conditional on improvement of its cost-effectiveness to an acceptable level. The committee was satisfied with the clinical benefit of the drug based on significant improvements in OS and PFS compared to treatment with lapatinib and capecitabine, however Kadcyla was not considered cost-effective at the undisclosed submitted price.
The committee assessed results from the EMILIA trial investigating Kadcyla compared to lapatinib and capecitabine treatment, considered to be a standard second-line treatment option for patients with metastatic breast cancer. The pERC noted that the magnitude of improvement in OS and PFS in the trial was "very meaningful", and particularly significant in a population that has previously been treated for a metastatic indication.
With regards to cost effectiveness, at the list price Kadcyla costs CAD2,508 (USD2301.97) per 100 mg vial, or CAD8,426.88 per 28-day treatment, while lapatinib and capecitabine treatment costs CAD4,064.29 for a 28-day course of treatment. The confidential submitted price for Kadcyla used to make the economic analysis was still considered not cost-effective compared to lapatinib and capecitabine treatment. The full reimbursement decision can be found here.
Roche's Erivedge
The pERC has issued a positive recommendation to fund Roche's Erivedge as a treatment in patients with metastatic or locally advanced basal cell carcinoma (BCC) that are inappropriate for surgery or radiotherapy, conditional on the improvement of its cost-effectiveness to an acceptable level. The recommendation was based on clinical evidence for improvement in objective response rates (43% metastatic and 30% locally advanced) with treatment in a patient population with few treatment options and no comparative evidence. However, the non-randomised, non-comparative mid-stage study design created uncertainty regarding the magnitude of clinical benefit, and cost-effectiveness of vismodegib. The comparison of vismodegib at the submitted price compared to a range of estimates for best supportive care did not demonstrate cost-effectiveness for the drug. At the list price, Erivedge costs CAD294.22 per 150 mg, or CAD8,238.24 per 28-day course treatment.
According to the pERC, with the availability of Erivedge for the treatment of metastatic and locally advanced BCC in patients that are inappropriate for surgery or radiotherapy, an indication with currently no standard of care, there will likely be a "larger patient population to treat". The committee highlighted the potential for use of the drug outside its recommended indication, potentially significantly impacting drug plan budgets due to the high prevalence of BCC. In order to prevent "indication creep", the committee has urged jurisdictions to take steps to restrict prescribing to the recommended population, potentially implementing a multi-disciplinary team to authorise prescribing decisions. The full reimbursement decision can be found here.
Outlook and implications
The unfavourable recommendation for Erbitux is a setback for BMS, however the committee seems to be waiting for results from the CALGB-C80405 study that could shed light on the drug's efficacy compared to Roche's Avastin (bevacizumab), currently considered the standard of care for first-line treatment of mCRC. Erbitux is already used as a third-line treatment, and alterations in the sequence of treatment may impact current "algorithms" and entail earlier testing for K-RAS mutations that the committee notes would increase costs. Colorectal cancer is the second most common cause of cancer-death in Canada, and the pERC highlighted the need for treatments that significantly improve survival.
While Roche's Kadcyla and Erivedge received more favourable recommendations from the pERC, the firm will probably be under pressure as individual jurisdictions aim to negotiate lower prices to improve the cost-effectiveness of the drug, as per the pERC's recommendations. The efficacy of Kadcyla was significant compared to treatment with GlaxoSmithKline's (UK) Tykerb/Tyverb (lapatinib) and capecitabine, however with regards to Erivedge, the committee seemed to raise concerns regarding the design of the trials used and the resulting "uncertainty" around the magnitude of clinical benefit. In the case of Erivedge, the pERC has recommended individual jurisdictions obtain a "substantial reduction in drug price" in order to offset this uncertainty and improve cost-effectiveness of the drug, although no current standard treatment currently exists for the indication in question. The pERC funding recommendations are taken into account by drug plans across Canada, except in the province of Quebec.