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Relevant comparators
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| The EMPOWER-Lung 1 trial comparator was platinum-doublet chemotherapy. This is likely not the most relevant comparator anymore. Should the relevant comparator be pembrolizumab alone or in combination with chemotherapy? How about nivolumab plus ipilimumab in combination with chemotherapy (not yet funded, but has a positive CADTH recommendation)? | According to the clinical experts, the most relevant comparator is pembrolizumab alone. On an individual level, the choice would be between cemiplimab monotherapy and pembrolizumab monotherapy. If a patient and/or clinician were to choose a treatment other than pembrolizumab monotherapy, there would be no compelling reason for them to consider cemiplimab monotherapy over that treatment. pERC agreed with the clinical experts. |
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Considerations for initiation of therapy
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| There was about a 70% crossover rate from the chemotherapy alone arm to receive cemiplimab. Should subsequent line treatment be made available on a time-limited basis for patients who would not have had the chance to receive cemiplimab in the first line? And if so, would this only be extended to patients who received chemotherapy alone? | The clinical experts indicated that, in clinical practice, most patients receive immunotherapy alone or in combination with chemotherapy in the first-line setting. Patients who have not received immunotherapy in first-line should be considered to receive it second line (unless contraindicated). Available second-line options are pembrolizumab, nivolumab and atezolizumab. Second-line single drug immunotherapy is readily available in all provinces for patients who progress on chemotherapy. The EMPOWER-Lung 1 data should not be extended to the second-line setting. pERC agreed with the clinical experts and considered that patients who have not received first-line immunotherapy, including those who received chemotherapy alone, should not be eligible for cemiplimab treatment in the second-line setting as it is indicated for the first-line setting only and there is no evidence to support its use in subsequent lines. |
| In the EMPOWER-Lung 1 trial, at time of progression, patients were permitted to continue cemiplimab with the addition of histology-specific chemotherapy for up to 4 cycles. In clinical practice, should cemiplimab be continued beyond progressive disease as per the EMPOWER-Lung 1 trial? | The clinical experts noted that, in clinical practice, patients may continue immunotherapy for clinical benefit beyond disease progression. Adding chemotherapy to immunotherapy at disease progression remains investigational. Based on the small number of patients from the EMPOWER-Lung 1 trial that had chemotherapy added to immunotherapy, no definitive conclusions can be derived. At present, the addition of chemotherapy to immunotherapy at disease progression is not funded. pERC agreed with the clinical experts, noting that there is no evidence to support the addition of chemotherapy to immunotherapy at disease progression. |
| Patients who were never smokers were not eligible for the EMPOWER-Lung 1 trial. Should they be excluded if funded? | The clinical experts noted that never smokers should not be excluded from treatment with cemiplimab. However, since they were excluded from the EMPOWER-Lung 1 trial, there is a lack of evidence on cemiplimab treatment outcomes for this population. pERC agreed with the clinical experts that never smokers should not be excluded from treatment with cemiplimab. |
| Are patients who had previous adjuvant or neoadjuvant chemotherapy eligible to receive cemiplimab as was allowed in the EMPOWER-Lung 1 trial? | The clinical experts indicated that patients who had previous adjuvant or neoadjuvant chemotherapy or immunotherapy should be eligible to receive cemiplimab. In the EMPOWER-Lung 1 trial, patients had to be 6 months post adjuvant/neo adjuvant chemotherapy to be eligible to participate. pERC agreed with the clinical experts and considered that patients who received previous adjuvant or neoadjuvant chemotherapy should be eligible to receive cemiplimab. In addition, patients who progress at least 6 months after their last dose of immunotherapy should be eligible to receive cemiplimab. |
| If a patient receives 108 weeks of treatment and subsequently relapses, should they be eligible for retreatment and if so, would there be a maximum duration? | According to the clinical experts, patients should be eligible for retreatment for 17 cycles (1 year) if extrapolating from the KEYNOTE-024 trial that allowed retreatment for patients who stopped immune therapy early (before 2 years) because of complete response or for patients who completed 2 years of immune therapy and subsequently progressed. pERC agreed with the clinical experts that patients who completed 2 years of cemiplimab treatment and subsequently progressed and patients who discontinued cemiplimab after less than 2 years due to complete response should be eligible for retreatment for up to 17 cycles (1 year). |
| If a patient discontinues treatment before the completion of 108 weeks due to toxicity, but without relapse, could they restart and be treated to a maximum of 108 weeks? | pERC agreed with the clinical experts that patients who discontinue treatment before completion due to toxicity can restart treatment as long as the toxicity has resolved. |
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Considerations for prescribing of therapy
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| In the EMPOWER-Lung 1 trial, the dose is 350 mg IV over 30 minutes every 3 weeks until progressive disease or 108 weeks (36 treatments – approximately 2 years). Is the 3 mg/kg IV over 30 minutes every 2 weeks dosing option for patients with low body weight currently available for advanced cutaneous squamous cell carcinoma also recommended for patients with NSCLC? | The clinical experts noted that there is limited evidence to inform on alternative dosages other than that used in the EMPOWER trial. Ideally, the fixed dose used in the clinical trial should be used. The weight-based dosing would be based on extrapolation from other disease settings. pERC agreed with the clinical experts. |
| Consider alignment with prescribing criteria for pembrolizumab and nivolumab/ipilimumab. | pERC considered this statement in their deliberations. |
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Generalizability
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| In the EMPOWER trial, patients had an ECOG-PS of 0 or 1. Can patients with ECOG-PS > 1 be considered eligible? | pERC agreed with the clinical experts that patients with ECOG-PS up to 2 may be considered for eligibility based on data showing efficacy of other treatments such as chemotherapy in these patients. |
| Should treatment be funded for patients who have had pembrolizumab or nivolumab plus ipilimumab in combination with chemotherapy and wish to switch to cemiplimab on a time-limited basis? | According to the clinical experts, switching is not generally necessary. If patients did not progress on pembrolizumab or nivolumab plus ipilimumab, there is no benefit in switching to cemiplimab. pERC agreed with the clinical experts and did not consider it necessary to fund cemiplimab treatment for patients who have not progressed on pembrolizumab or nivolumab plus ipilimumab. |
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Funding algorithm
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| PAG would like to note that other immune checkpoint inhibitors will not be funded in patients that experience disease progression while receiving cemiplimab. | pERC considered this statement in their deliberations. |
| Under what conditions would cemiplimab use be preferred over pembrolizumab, or nivolumab plus ipilimumab in combination with chemotherapy? | The clinical experts indicated that with similar efficacy and toxicity profiles, the choice of first-line immunotherapy as monotherapy will be based on access and physician choice. Similarly, the decision of first-line monotherapy vs. immunotherapy-chemotherapy combination will be based on access, toxicity considerations, and volume of disease (ultimately physician choice) in the absence of evidence-based comparison data. Longer-term follow-up data supports the use of pembrolizumab over cemiplimab. If funding allowed cemiplimab to continue with the addition of 4 cycles of chemotherapy at the time of progression, this would make it appealing to clinicians. pERC agreed with the clinical experts’ response, except that they noted that the addition of 4 cycles of chemotherapy to cemiplimab at the time of disease progression should not be funded given the lack of evidence for this approach. |
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Care provision issues
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| Pembrolizumab is currently reimbursed for this indication and nivolumab plus ipilimumab in combination with chemotherapy is currently undergoing price negotiations. | pERC considered this statement in their deliberations. |
