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National Institute for Health and Care Excellence
Single Technology Appraisal (STA)
Pembrolizumab with lenvatinib for previously treated advanced, metastatic or recurrent endometrial cancer ID3811
Response to consultee and commentator comments on the draft remit and draft scope (pre-referral)
Please note: Comments received in the course of consultations carried out by NICE are published in the interests of openness and transparency, and to promote understanding of how recommendations are developed. The comments are published as a record of the submissions that NICE has received, and are not endorsed by NICE, its officers or advisory committees.
Comment 1: the draft remit
| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| Wording Does the wording of the remit reflect the issue(s) of clinical and cost effectiveness about this technology or technologies that NICE should consider? If not, please suggest alternative wording. |
Eisai | Lenvima, in combination with pembrolizumab, is indicated for the treatment XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXX Therefore we suggest alternative wording as below: “To appraise the clinical and cost effectiveness of lenvatinib with pembrolizumab within its marketing authorisationXXXXXXXXX XXXXXXXXXXXXX |
Comment noted. The remit has been kept broad but notes that the technology will be appraised within its marketing authorisation. |
| MSD | KEYTRUDA, in combination with lenvatinib,XXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXX |
Comment noted. The remit has been kept broad but notes that the technology will be appraised within its marketing authorisation. |
National Institute for Health and Care Excellence
Consultation comments on the draft remit and draft scope for the technology appraisal of pembrolizumab with lenvatinib for previously treated advanced, metastatic or recurrent endometrial cancer
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| British Gynaecological Cancer Society (BGCS) |
Yes | Comment noted. No action required. |
|
| Timing Issues What is the relative urgency of this appraisal to the NHS? |
Eisai | The provisional scheduling for this topic is appropriate. | Comment noted. No action required. |
| MSD | We anticipate that the proposed appraisal should be scheduled to enable NICE to issue final guidance soon after regulatory approval. Information regarding anticipated regulatory timelines presented in UK PharmaScan accurately reflect current expectations. |
Comment noted. No action required. |
|
| BGCS | Disease progression following chemotherapy for advanced ovarian cancer is often not well controlled by further cytotoxic chemotherapy and other therapeutic strategies are urgently needed. |
Comment noted. This appraisal has been scheduled into the work programme. |
Comment 2: the draft scope
| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| Background information Consider the accuracy and completeness of this information. |
Eisai | Background information is accurate and complete. | Comment noted. No action required. |
| MSD | No further comment | Comment noted. No action required. |
National Institute for Health and Care Excellence
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| BGCS | Yes | Comment noted. No action required. |
|
| The technology/ intervention Is the description of the technology or technologies accurate? |
Eisai | The description of the technology is not accurate. Please use the following alternative wording: “Lenvatinib (Lenvima, Eisai) is a multi-kinase inhibitor. This selectively inhibits the kinase activities of all vascular endothelial growth factor receptors, in addition to other proangiogenic and oncogenic pathways, including fibroblast growth factor receptors, the platelet derived growth factor receptor alpha KIT and RET. It is administered orally.” |
The description of the technology section aims to provide a brief summary of the technology and is not designed to be exhaustive. The brand name of lenvatinib (Lenvima) was added. |
| MSD | No further comment | Comment noted. No action required. |
|
| BGCS | Yes | Comment noted. No action required. |
|
| Population Is the population defined appropriately? Are there groups within this population that should be considered separately? |
Eisai | The population is not defined appropriately and needs to be in line with proposed indication wording as below: “XXXXXXXXXXXXXXXXXXXXXX |
The population description has been updated in line with the marketing authorisation. |
| MSD | No further comment | Comment noted. | |
| Comparators | Eisai | There is no clear standard of care in people with advanced endometrial cancer who have received prior systemic treatment. |
Comments noted. Stakeholders’ opinions recently gathered for |
National Institute for Health and Care Excellence
Consultation comments on the draft remit and draft scope for the technology appraisal of pembrolizumab with lenvatinib for previously treated advanced, metastatic or recurrent endometrial cancer
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| Is this (are these) the standard treatment(s) currently used in the NHS with which the technology should be compared? Can this (one of these) be described as ‘best alternative care’? |
We suggest the comparators for the appraisal should be: • Doxorubicin BGCS guidelines1suggest doxorubicin can be used in the second line setting • Carboplatin with paclitaxel BGCS guidelines suggest carboplatin + paclitaxel can be considered in fit patients as a re-challenge if the treatment free-interval is more than six months. • Cisplatin with paclitaxel Clinical experts have suggested cisplatin with paclitaxel may be an option for when a platinum combination is considered. • Weekly paclitaxel We suggest the removal of weekly paclitaxel as the evidence is only supported by anecdotal evidence as stated by the BGCS and it’s listing as an option is based upon ovarian cancer activity. • Cyclophosphamide We suggest the removal of cyclophosphamide as the BGCS guidelines state this is an option in the first line setting for fit patients with disseminated recurrent disease. The pivotal phase III study relates to previously treated patients. • Hormone therapy We suggest that hormone therapy is removed from the comparators, as per BGCS guidelines, this treatment is used for patients not fit for chemotherapy. One inclusion criteria for the pivotal phase III study is that patients have to have an ECOG performance status of 0 or 1. The guidelines also state “there is no evidence that hormonal treatment in patients with advanced or recurrent endometrial cancer improves overall survival”. |
this disease area noted that there are no universal standards for treatments of patients with advanced endometrial. However, currently some treatment options are available for patients. Therefore, the following comparators have been included in the updated scope: Chemotherapy, including: • carboplatin with paclitaxel; • paclitaxel monotherapy; • doxorubicin monotherapy; and • carboplatin monotherapy; Hormone therapy, and Best supportive care. The following comparators have been |
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National Institute for Health and Care Excellence
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| excluded from the updated scope: cyclophosphamide and cisplatin. |
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| MSD | We suggest the comparators for the appraisal should be: • Doxorubicin BGCS guidelines suggest doxorubicin can be used in the second line setting • Carboplatin with paclitaxel BGCS guidelines suggest carboplatin + paclitaxel can be considered in fit patients as a re-challenge if the treatment free-interval is more than six months. • Cisplatin with paclitaxel Clinical experts have suggested cisplatin with paclitaxel may be an option for when a platinum combination is considered. Clinical experts have stated there is no clear standard of care for those who have had previous systemic treatment for advanced, recurrent or metastatic endometrial cancer. • Weekly paclitaxel We suggest the removal of weekly paclitaxel as the evidence is only supported by anecdotal evidence as stated by the BGCS and it’s listing as an option is based upon ovarian cancer activity. • Cyclophosphamide |
Comments noted. Stakeholders’ opinions recently gathered for this disease area noted that there are no universal standards for treatments of patients with advanced endometrial cancer. However, currently some treatment options are available for patients. Therefore, the following comparators have been included in the updated scope: Chemotherapy, including: • carboplatin with paclitaxel; |
1 BGCS Uterine Cancer Guidelines: Recommendations for Practice, 2017 National Institute for Health and Care Excellence
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| We suggest the removal of cyclophosphamide as the BGCS guidelines state this is an option in the first line setting for fit patients with disseminated recurrent disease. KEYNOTE-775 relates to previously treated patients. • Hormone therapy We suggest that hormone therapy is removed from the comparators, as per BGCS guidelines, this treatment is used for patients not fit for chemotherapy. One inclusion criteria for KEYNOTE-775 was patients had to have a ECOG performance status of 0 or 1. The guidelines also state “there is no evidence that hormonal treatment in patients with advanced or recurrent endometrial cancer improves overall survival |
• paclitaxel monotherapy; • doxorubicin monotherapy; and • carboplatin monotherapy; Hormone therapy, and Best supportive care. The following comparators have been excluded from the updated scope: cyclophosphamide and cisplatin. |
||
| BGCS | Yes | Comment noted. No action required. |
|
| Outcomes Will these outcome measures capture the most important health related benefits (and harms) of the technology? |
Eisai | The outcome measures listed are appropriate. | Comment noted. No action required. |
| MSD | To include duration of response | Comment noted. Duration of response |
National Institute for Health and Care Excellence
Consultation comments on the draft remit and draft scope for the technology appraisal of pembrolizumab with lenvatinib for previously treated advanced, metastatic or recurrent endometrial cancer
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| has been added as an outcome measure. |
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| Economic analysis Comments on aspects such as the appropriate time horizon. |
Eisai | No comment | Comment noted. No action required. |
| MSD | No further comment | Comment noted. No action required. |
|
| Equality and Diversity NICE is committed to promoting equality of opportunity, eliminating unlawful discrimination and fostering good relations between people with particular protected characteristics and others. Please let us know if you think that the proposed remit and scope may need changing in order to meet these aims. In particular, please tell us if the proposed remit and scope: • could exclude from full consideration any people |
Eisai | No comment | Comment noted. No action required. |
| MSD | None identified, no further comment. | Comment noted. No action required. |
|
| BGCS | I am not aware of any issues | Comment noted. No action required. |
National Institute for Health and Care Excellence
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| protected by the equality legislation who fall within the patient population for which [the treatment(s)] is/are/will be licensed; • could lead to recommendations that have a different impact on people protected by the equality legislation than on the wider population, e.g. by making it more difficult in practice for a specific group to access the technology; • could have any adverse impact on people with a particular disability or disabilities. Please tell us what evidence should be obtained to enable the Committee to identify and consider such impacts. |
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| Other considerations |
Eisai | No comment | Comment noted. No action required. |
National Institute for Health and Care Excellence
Consultation comments on the draft remit and draft scope for the technology appraisal of pembrolizumab with lenvatinib for previously treated advanced, metastatic or recurrent endometrial cancer
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| Suggestions for additional issues to be covered by the appraisal are welcome. |
MSD | No further comment | Comment noted. No action required. |
| Innovation Do you consider the technology to be innovative in its potential to make a significant and substantial impact on health-related benefits and how it might improve the way that current need is met (is this a ‘step- change’ in the management of the condition)? Do you consider that the use of the technology can result in any potential significant and substantial health- related benefits that are unlikely to be included in the QALY calculation? Please identify the nature of the data which you |
Eisai | Eisai do consider lenvatinib to be innovative as it is a multiple receptor tyrosine kinase (RTK) inhibitor with a novel, distinct binding mode that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet- derived growth factor [PDGF] receptor PDGFRα; KIT; and RET) involved in tumour proliferation. Furthermore, when used in combination with pembrolizumab, the immunomodulatory effects of lenvatinib i.e. the suppression of monocytes and macrophages and proliferation of CD8+ T cell populations are thought to enhance the overall antitumor effect of the combination treatment. There is a high unmet need in patients with advanced endometrial cancer. No novel therapies have been licensed for use in endometrial cancer for nearly 50 years, despite a growing incidence of the disease. As highlighted above, there is no current clear standard of care for patients with advanced endometrial cancer who have received previous treatment and therefore Eisai considers lenvatinib and pembrolizumab to be a “step-change” in the management of the condition. |
Comment noted. No action required. |
| MSD | MSD considers lenvatinib + pembrolizumab to be innovative in its potential to make a significant and substantial positive impact on health-related benefits. |
Comment noted. No action required. |
National Institute for Health and Care Excellence
Consultation comments on the draft remit and draft scope for the technology appraisal of pembrolizumab with lenvatinib for previously treated advanced, metastatic or recurrent endometrial cancer
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| understand to be available to enable the Appraisal Committee to take account of these benefits. |
Lenvatinib + pembrolizumab has the potential to improve outcomes for patients who have received previous treatment in adults with advanced endometrial cancer. |
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| BGCS | Yes. Data exist for benefit with immunotherapy in advanced endometrial cancer but a large proportion of patients do not respond or later develop resistance. By targeting abnormal tumour blood vessel formation VEGF inhibition may increase infiltration of immune effector cells and there may be synergistic effects of combined treatment in endometrial cancer which can improve outcomes. |
Comment noted. No action required. |
|
| Questions for consultation Please answer any of the questions for consultation if not covered in the above sections.If appropriate, please include comments on the proposed process this appraisal will follow (please note any changes made to the process are likely to result in changes to the planned timelines). |
Eisai | Is the population in the scope defined appropriately? No, please see comments above Have all relevant comparators for lenvatinib with pembrolizumab been included in the scope? Please see comments above Which treatments are considered to be established clinical practice in the NHS for previously treated advanced, metastatic and recurrent endometrial cancer? How should best supportive care be defined? Please see comments above Are the outcomes listed appropriate? Yes Are there any subgroups of people in whom lenvatinib with pembrolizumab is expected to be more clinically effective and cost effective or other groups that should be examined separately? |
Comment noted. |
National Institute for Health and Care Excellence
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| At present there are no sub-groups that have been identified where lenvatinib with pembrolizumab will be more clinically and cost effective. Where do you consider lenvatinib with pembrolizumab will fit into the existing NICE pathway for endometrial cancer, Urogenital conditions? We anticipate that lenvatinib with pembrolizumab will be used in people with previously treated advanced endometrial cancer. NICE is committed to promoting equality of opportunity, eliminating unlawful discrimination and fostering good relations between people with particular protected characteristics and others. Please let us know if you think that the proposed remit and scope may need changing in order to meet these aims. No anticipated impact Do you consider lenvatinib with pembrolizumab to be innovative in its potential to make a significant and substantial impact on health-related benefits and how it might improve the way that current need is met (is this a ‘step-change’ in the management of the condition)? Yes, please see comments above. Do you consider that the use of lenvatinib with pembrolizumab can result in any potential significant and substantial health-related benefits that are unlikely to be included in the QALY calculation? We do not currently consider that there will be substantial health-related benefits that are unlikely to be included in the QALY calculation. |
National Institute for Health and Care Excellence
Consultation comments on the draft remit and draft scope for the technology appraisal of pembrolizumab with lenvatinib for previously treated advanced, metastatic or recurrent endometrial cancer
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| To help NICE prioritise topics for additional adoption support, do you consider that there will be any barriers to adoption of this technology into practice? None anticipated |
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| MSD | Is the population in the scope defined appropriately? Yes Have all relevant comparators for lenvatinib with pembrolizumab been included in the scope? See comments above Which treatments are considered to be established clinical practice in the NHS for previously treated advanced, metastatic and recurrent endometrial cancer? How should best supportive care be defined? See comments above Are the outcomes listed appropriate? Inclusion of duration of response is suggested Are there any subgroups of people in whom lenvatinib with pembrolizumab is expected to be more clinically effective and cost effective or other groups that should be examined separately? At present there are no sub-groups that have been identified where lenvatinib with pembrolizumab will be more clinically and cost effective. |
Comment noted. |
National Institute for Health and Care Excellence
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| Where do you consider lenvatinib with pembrolizumab will fit into the existing NICE pathway for endometrial cancer, Urogenital conditions? We anticipate that lenvatinib with pembrolizumab will be used for people who have had previous systemic treatment for advanced, recurrent or metastatic endometrial cancer NICE is committed to promoting equality of opportunity, eliminating unlawful discrimination and fostering good relations between people with particular protected characteristics and others. Please let us know if you think that the proposed remit and scope may need changing in order to meet these aims. No anticipated impact Do you consider lenvatinib with pembrolizumab to be innovative in its potential to make a significant and substantial impact on health-related benefits and how it might improve the way that current need is met (is this a ‘step-change’ in the management of the condition)? Yes Do you consider that the use of lenvatinib with pembrolizumab can result in any potential significant and substantial health-related benefits that are unlikely to be included in the QALY calculation? We do not consider that there will be substantial health-related benefits that are unlikely to be included in the QALY calculation. To help NICE prioritise topics for additional adoption support, do you consider that there will be any barriers to adoption of this technology into practice? |
National Institute for Health and Care Excellence
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| Section | Consultee/ Commentator |
Comments [sic] | Action |
|---|---|---|---|
| None anticipated |
The following consultees/commentators indicated that they had no comments on the draft remit and/or the draft scope Pfizer
National Institute for Health and Care Excellence
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