Drugs, Health Technologies, Health Systems
Indication: For the treatment of adult patients with Stage III or metastatic small cell lung cancer (SCLC) who have progressed on or after platinum-containing therapy.
Sponsor: Jazz Pharmaceuticals Canada Incorporated
Final recommendation: Reimburse with conditions
This recommendation is time-limited and contingent on a reassessment of additional evidence.
Summary
What Is the Reimbursement Recommendation for Zepzelca?
Canada’s Drug Agency (CDA-AMC) recommends that Zepzelca should be reimbursed by public drug plans for the treatment of adult patients with stage III or metastatic small cell lung cancer (SCLC) who have progressed on or after platinum-containing therapy for a time-limited period while additional evidence is generated and if certain conditions are met.
Please note that time-limited reimbursement refers to temporary reimbursement by the drug programs while additional evidence is generated and submitted for reassessment (i.e., this does not refer to the length of treatment or number of cycles administered).
Which Patients Are Eligible for Coverage?
Zepzelca should only be covered to treat adult patients whose disease has relapsed or who have refractory stage III or metastatic SCLC, have received 1 prior line of platinum-based therapy, and are in good performance status. Zepzelca should not be used for patients with active (untreated) central nervous system disease, who are pregnant, and for those who received more than 1 prior line of therapy.
What Are the Conditions for Reimbursement?
Zepzelca should only be reimbursed if prescribed by a clinician with expertise in managing SCLC, treatment should be delivered in outpatient specialized oncology clinics with expertise in systemic therapy delivery, and the cost of Zepzelca is reduced.
Why Did CDA-AMC Make This Recommendation?
Evidence from a single-arm phase II trial (B-005) could not inform on the relative clinical value of Zepzelca versus drugs usually prescribed to the target patient population due to the noncomparative single-arm design.
While results from 4 indirect treatment comparisons (ITCs) showed possible improvements in overall survival (OS), progression-free survival (PFS), and safety among patients receiving Zepzelca compared to relevant comparators, all ITCs were affected by methodological limitations resulting in the inability to confidently draw conclusions on the efficacy and safety of Zepzelca versus comparators.
One real-world retrospective observational study evaluated the effectiveness and safety of Zepzelca versus other second-line treatments (e.g., platinum rechallenge, topotecan, immunotherapy). This study showed that Zepzelca may result in little to no difference in real-world response rate and real-world PFS at 6 months compared to other second-line treatments, although the evidence is very uncertain due to variability and risk of skewing results.
There is a significant unmet clinical need for patients with previously treated recurrent or metastatic SCLC because currently available treatments have limited effectiveness and substantial toxicities. While the current evidence is insufficient to conclude that these needs are addressed by Zepzelca, uncertainty could be alleviated if the results of the upcoming phase III LAGOON trial demonstrate similar or better survival rates of patients treated with Zepzelca versus relevant comparators. Further, the administration of Zepzelca may be easier compared with other therapies used for SCLC, which may improve patients’ health-related quality of life (HRQoL), an outcome that will be measured in the LAGOON study.
The Zepzelca evidence generation plans may address the uncertainty in the afforded clinical benefits and value for money. Consequently, reimbursement of Zepzelca for a limited time would be appropriate while this evidence develops. CDA-AMC will examine the LAGOON study results when they become available and will then reassess and finalize its reimbursement recommendation.
Based on the CDA-AMC assessment of the health economic evidence, Zepzelca does not represent good value to health care systems at the public list price. The committee determined that there is not enough evidence to justify a greater cost for Zepzelca compared with comparators for the same indication.
Based on public list prices, Zepzelca is estimated to cost the public drug plans approximately $98.8 million over the next 3 years.
Additional Information
What Is SCLC?
SCLC is a fast-growing type of lung cancer that predominantly affects people with a history of smoking tobacco. SCLC is classified as metastatic when the cancer cells have spread from the lungs to other parts of the body such as the brain, bones, or liver. In 2024, an estimated 32,100 people living in Canada were expected to be diagnosed with lung cancer with SCLC accounting for 10% to 15% of diagnoses.
Unmet Needs in SCLC
Patients indicated that currently available treatments are associated with suboptimal disease control, common and severe side effects, and have inconvenient administration schedules. Therefore, there remains a substantial unmet need for a well-tolerated, convenient, and effective drug for patients with previously treated SCLC.
How Much Does Zepzelca Cost?
Treatment with Zepzelca is expected to cost approximately $33,507 per patient per 28-day cycle, based on the Health Canada–recommended dosage and assuming 1.8 m2 body surface area.
Disease background: SCLC is a fast-growing type of lung cancer that predominantly affects people with a history of smoking tobacco. SCLC is classified as metastatic when the cancer cells have spread from the lungs to other parts of the body such as the brain, bones, or liver.
In 2024, an estimated 32,100 people living in Canada were expected to be diagnosed with lung cancer and SCLC accounts for 10% to 15% of diagnoses.
Indication and reimbursement request: Lurbinectedin (Zepzelca) has been conditionally approved by Health Canada for the treatment of adult patients with stage III or metastatic SCLC who have progressed on or after platinum-containing therapy. The sponsor is seeking reimbursement for the second-line treatment of adult patients with stage III or metastatic SCLC who have progressed on or after a platinum-containing therapy.
Drug under review: Lurbinectedin is an alkylating agent. It is administered by IV infusion and the dosage recommended in the product monograph is 3.2 mg/m2 for 1 hour every 21 days until disease progression or unacceptable toxicity.
Treatment costs: At the submitted price of $12,565.25 per 4 mg vial, the per 28-day cost of lurbinectedin is expected to be $33,507 per patient, based on the Health Canada–recommended dosage and assuming 1.8 m2 body surface area.
Eligibility for a time-limited recommendation: Based on the preliminary assessment by CDA-AMC, lurbinectedin met the criteria to be considered by the pan-Canadian Oncology Drug Review Expert Review Committee (pERC) for a time-limited reimbursement recommendation.
Submission history: Lurbinectedin was previously reviewed by CDA-AMC and received a recommendation not to reimburse from pERC on January 12, 2023, for the treatment of adult patients with stage III or metastatic SCLC who have progressed on or after platinum-containing therapy. The original review of lurbinectedin included 1 phase II trial (B-005; N = 105) reporting the efficacy and safety of lurbinectedin and 3 ITCs comparing lurbinectedin to a basket of second-line treatments (e.g., platinum rechallenge; platinum with etoposide; cyclophosphamide, doxorubicin, and vincristine; topotecan; or other), topotecan, and carboplatin plus etoposide. pERC’s rationale to recommend not reimbursing lurbinectedin in 2023 included uncertainty in the magnitude of any clinical benefit, uncertainty in the efficacy and safety of lurbinectedin versus relevant comparators, unknown effect of lurbinectedin on HRQoL — an important outcome to patients, and the lack of evidence indicating lurbinectedin addresses the unmet needs identified by patients.
Basis of resubmission: In this resubmission, the sponsor narrowed the reimbursement request to focus only on second-line treatment and requested that the file be considered under the time-limited reimbursement pathway. This resubmission is based on new evidence from real-world settings and an ITC to address gaps identified by pERC in the initial submission. The totality of evidence, including that submitted for the initial review and this resubmission, was considered by the expert committee during their deliberations.
The patient groups (Lung Cancer Canada, Lung Health Foundation, and Canadian Cancer Survivor Network) noted the following regarding impacts of the disease, unmet needs, and important outcomes:
Patients highlighted the physical burden of the disease including fatigue, breathlessness, persistent cough, pain, nausea, and rapid functional decline. The impact of late diagnosis, worry of progression, and distress of the limited options available contributed to the emotional burden of SCLC.
Prolonging survival, stopping or delaying disease progression, and maintaining quality of life with reduced symptoms are the most important outcomes for patients.
The clinician groups (Ontario Health [Cancer Care Ontario] Lung and Thoracic Cancer Drug Advisory Committee and Lung Cancer Canada – Medical Advisory Committee) and the clinical experts consulted by CDA-AMC noted the following regarding unmet needs arising from the disease and place in therapy for the drug under review:
Experts noted a substantial unmet need for a well-tolerated (i.e., low toxicity), convenient, and effective drug in the second-line SCLC setting.
The clinical experts consulted for this review and the clinician groups felt lurbinectedin would offer an alternative second-line and third-line treatment option for patients with SCLC following first-line platinum-containing chemotherapy. However, third-line therapy is not included in the present reimbursement request.
The participating public drug programs raised potential implementation issues related to considerations for initiation and prescribing of therapy, generalizability of trial populations to broader populations, care provision issues, system and economic issues, and the potential need for a provisional funding algorithm.
This recommendation supersedes the pERC recommendation for this drug and indication dated January 12, 2023.
With a vote of 14 in favour to 3 against, pERC recommends that lurbinectedin be reimbursed for the second-line treatment of adult patients with stage III or metastatic SCLC who have progressed on or after a platinum-containing therapy for a time-limited period while additional evidence is generated and only if the conditions listed in Table 1 are met.
Table 1: Reimbursement Conditions and Reasons
Reimbursement condition | Reason | Implementation guidance |
|---|---|---|
Initiation | ||
1. Treatment with lurbinectedin should be reimbursed in adult patients (18 years or older) who have: 1.1. Disease relapse or refractory stage III or metastatic SCLC 1.2. Received 1 prior platinum-based therapy 1.3. Good performance status. | These characteristics reflect patient characteristics in Study B-005 as patients in the study had progressed on or after receiving 1 prior platinum-containing chemotherapy and had to have an ECOG PS score of 0 to 2. | The decision to treat patients with lurbinectedin vs. rechallenging with platinum-based chemotherapy should be left up to the treating physician and patient as the effects of lurbinectedin are similar regardless of the chemotherapy-free interval. Patients who received platinum or etoposide at any time for limited stage SCLC and then progressed to extensive stage would be eligible for lurbinectedin. Patients with an adequate ECOG PS may be treated at the discretion of the treating clinician. Patients who are currently receiving second-line treatment with other chemotherapy regimens may be switched to lurbinectedin at time of funding. |
2. Patients must not have the following criteria: 2.1. Active (untreated) CNS disease 2.2. Person who is pregnant (potential teratogen) 2.3. Received more than 1 prior therapy (i.e., beyond second line). | Study B-005 excluded patients with known CNS involvement, patients who were pregnant or breastfeeding, or patients not using an effective method of contraception. The sponsor’s reimbursement request excludes third-line patients. | Patients who can become pregnant should be advised to avoid becoming pregnant while receiving lurbinectedin because it can cause embryonic or fetal toxicity. |
Discontinuation | ||
3. Reimbursement of lurbinectedin should be continued until progression or unacceptable toxicity, whichever occurs first. | Patients in Study B-005 discontinued treatment upon disease progression or unacceptable toxicity. | Clinical evaluations should be performed as per standard clinical assessment (typically CT restaging with or without bone scan every 3 to 4 months). |
Prescribing | ||
4. Lurbinectedin should be prescribed by a clinician with expertise in managing SCLC. Treatment should be delivered in outpatient specialized oncology clinics with expertise in systemic therapy delivery. | This is meant to ensure that lurbinectedin is prescribed for appropriate patients and that adverse effects are managed in an optimized and timely manner. | — |
Pricing | ||
5. The total cost of lurbinectedin should be negotiated to not exceed the total cost of treatment with the least costly comparator for the same indication. | Based on the committee’s assessment of the evidence, lurbinectedin is not expected to provide superior clinical benefits or safety compared with relevant comparators. Therefore, the total cost of lurbinectedin should be no more than other available comparators. | — |
Time-limited reimbursement | ||
6. This recommendation in favour of reimbursement is time-limited and contingent on a future reassessment of additional evidence that addresses the uncertainty. | Uncertainty in current phase II evidence must be adequately addressed in the ongoing confirmatory phase III, randomized LAGOON trial. Specifically, evidence from the LAGOON trial needs to confirm the clinical benefit in OS and PFS. | The sponsor has stated that the primary completion of the LAGOON trial is estimated to occur in 2027. The sponsor has confirmed that the LAGOON trial results will be filed with CDA-AMC in accordance with the timelines and requirements for a reassessment as described in the Procedures for Reimbursement Reviews, which requires the reassessment to be filed with CDA-AMC no later than 270 calendar days after the completion date of the phase III trial. In accordance with the CDA-AMC procedures, the sponsor must keep CDA-AMC informed of any revisions to the anticipated timelines for the LAGOON trial. |
CDA-AMC = Canada’s Drug Agency; CNS = central nervous system; ECOG PS = Eastern Cooperative Oncology Group Performance Status; OS = overall survival; PFS = progression-free survival; SCLC = small cell lung cancer; vs. = versus.
Based on the totality of the submitted clinical evidence, pERC concluded that it is uncertain if second-line treatment with lurbinectedin demonstrates acceptable clinical value compared with appropriate comparators (cisplatin or carboplatin plus etoposide; topotecan; cyclophosphamide, doxorubicin, and vincristine; irinotecan with or without cisplatin or carboplatin) in patients with SCLC. Lurbinectedin is expected to be an alternative to these regimens. Acceptable clinical value refers to similar or added clinical benefit versus the mentioned comparators.
One noncomparative single-arm phase II trial (B-005) did not demonstrate that treatment with lurbinectedin results in similar or better clinical benefit in patients with SCLC who received 1 prior line of platinum-containing chemotherapy. At a median follow-up of 17.1 months, patients treated with lurbinectedin had a median OS of 9.3 months (95% confidence interval [CI], 6.3 months to 11.8 months). Per independent review committee, the median PFS was 3.5 months (95% CI, 2.6 months to 4.2 months), median overall response rate (ORR) was 30.5% (95% CI, 21.9% to 40.2%), and median duration of response (DoR) in patients who had a confirmed complete response or partial response as best overall response was 5.1 months (95% CI, 4.9 months to 6.4 months). The key limitation of the trial is the single-arm, noncomparative design, which precludes any conclusion of the relative clinical value of lurbinectedin versus drugs usually prescribed to the target patient population. Aiming to address this gap, the sponsor submitted 4 ITCs and 1 real-world evidence (RWE) study.
Overall, the 4 ITCs informed on the effects of lurbinectedin versus a basket of second-line treatments (e.g., platinum rechallenge; platinum with etoposide; cyclophosphamide, doxorubicin, and vincristine; topotecan; or other), topotecan, and carboplatin plus etoposide. While the results from the ITCs suggested possible improvements in efficacy (including OS and PFS) and safety outcomes among patients receiving lurbinectedin, all were affected by methodological limitations which resulted in the inability to determine any effects on the efficacy and safety of lurbinectedin versus comparators.
One real-world retrospective observations study using US-based electronic medical records evaluated the efficacy and safety of lurbinectedin versus other second-line treatments (e.g., platinum rechallenge, topotecan, immunotherapy). Results from this study suggested that lurbinectedin may result in little to no difference in real-world response rate and real-world PFS at 6 months compared to other second-line treatments, although the evidence is very uncertain due to wide CIs and risk of bias.
HRQoL, an outcome identified as important by both patients and clinical experts, was not assessed in any of the submitted evidence. Therefore, it remains unknown how HRQoL with lurbinectedin treatment compares with other available treatments.
Given the considerable methodologic limitations in the body of evidence reviewed, comparative clinical benefit of lurbinectedin versus relevant comparators is largely unknown. Further information on the committee’s discussion around clinical value is provided in the Summary of Deliberation section.
Based on clinician and patient input, pERC established that there was a significant unmet clinical need for effective and safe treatments for patients with previously treated recurrent or metastatic SCLC. These patients have aggressive disease, and current second-line therapies have limited effectiveness. Currently available treatments offer poor survival outcomes and cause substantial toxicity, while the disease severely impacts quality of life through pain, functional limitations, and emotional distress.
pERC concluded that the submitted evidence is insufficient to conclude that these unmet needs may be addressed by lurbinectedin with an acceptable level of certainty. However, this uncertainty could be alleviated if the results of the upcoming phase III LAGOON trial demonstrate similar or better survival rates of patients treated with lurbinectedin. Additionally, pERC noted that lurbinectedin offers easier administration compared with alternative therapies, which may improve patient HRQoL, an outcome that will be measured in the LAGOON study. Therefore, pERC recommends reimbursement of lurbinectedin on a time-limited basis, while phase III evidence develops.
Further information on the committee’s discussion around unmet clinical need is provided in the Summary of Deliberation section.
pERC noted that Health Canada has mandated that the sponsor complete a confirmatory trial (LAGOON) to inform on clinical benefit via PFS and OS outcomes. pERC determined that the evidence generation plans may address the gaps in the evidence including providing higher certainty evidence on the comparative efficacy and safety of lurbinectedin versus relevant comparators and impacts of lurbinectedin on HRQoL, such that reimbursement of lurbinectedin for a time-limited period would be appropriate given the uncertainty in the magnitude of clinical benefit and cost-effectiveness. pERC noted that this approach would help facilitate equitable and timely access to new treatments for patients while ensuring that treatments considered for public reimbursement adhere to a level of rigour that sufficiently demonstrates effectiveness, safety, and cost-effectiveness. The time-limited reimbursement strategy allows the integration of future clinical trial evidence to help shape stronger health policy and drug funding decisions when additional data are required. The sponsor has confirmed that the LAGOON trial results will be filed with CDA-AMC in accordance with the timelines and requirements for a reassessment as described in the Procedures for Reimbursement Reviews.
Due to the uncertainty in clinical value, pERC could not recommend whether to reimburse lurbinectedin based on clinical value alone. Therefore, they also considered whether lurbinectedin addresses a significant unmet clinical need. pERC concluded that lurbinectedin may address a significant unmet clinical need with an acceptable level of certainty if the upcoming results of the LAGOON trial support the clinical value of lurbinectedin. Based on the preceding considerations, pERC recommended that lurbinectedin be reimbursed on a time-limited basis, contingent on reassessment when the LAGOON trial results become available. As part of the deliberation on whether to recommend reimbursement, the committee also considered unmet nonclinical need and health inequity. Information on this discussion is provided in the Distinct Social and Ethical Considerations domain in the Summary of Deliberation section.
Because pERC recommended that lurbinectedin be reimbursed, the committee also deliberated on whether reimbursement conditions should be added to address important economic considerations, health system impacts, or social and ethical considerations, or to ensure clinical value is realized. The resulting reimbursement conditions, with accompanying reasons and implementation guidance, are stated in Table 1.
pERC considered all domains of value of the deliberative framework before developing its recommendation: clinical value, unmet clinical need, distinct social and ethical considerations, economic considerations, and impacts on health systems. For further information on the domains of value, refer to Expert Committee Deliberation at Canada’s Drug Agency.
The committee considered the following key discussion points, organized by the 5 domains of value.
Appropriate comparators: pERC noted that cisplatin or carboplatin plus etoposide; topotecan; cyclophosphamide, doxorubicin, and vincristine; and irinotecan with or without cisplatin or carboplatin were appropriate comparators for lurbinectedin in the target population.
Efficacy in the single-arm trial: pERC considered the single-arm phase II trial (B-005; n = 105). However, in the absence of a control group, the relative efficacy and safety of lurbinectedin versus other treatment options could not be determined from this trial.
Efficacy versus synthetic control arm: pERC discussed that results from the synthetic control arm analysis submitted as part of the initial submission was a naive comparison and therefore results are too uncertain to draw any conclusions.
Efficacy versus carboplatin plus etoposide: One matching-adjusted indirect comparison and network meta-analysis submitted as part of the initial submission was limited by imprecision, risk of bias, and residual confounding and therefore too uncertain to draw conclusions on the efficacy of lurbinectedin versus carboplatin and etoposide.
Efficacy versus topotecan: One indirect external control study was provided to inform the comparison of lurbinectedin versus topotecan. pERC discussed that in the unanchored naive comparison, generalizability concerns, and overlapping 95% CIs rendered the results for OS, PFS, ORR, and DoR inconclusive. Similarly, 1 simulated treatment comparison and 1 matching-adjusted indirect comparison and network meta-analysis submitted as part of the initial submission were limited by imprecision, risk of bias, and residual confounding and therefore too uncertain to draw conclusions on the efficacy of lurbinectedin versus topotecan.
Efficacy versus other second-line treatments: One retrospective observational real-world study demonstrated that lurbinectedin may result in little to no difference in real-world response rate and real-world PFS at 6 months compared to other second-line treatments (including platinum rechallenge, platinum with etoposide, topotecan, immunotherapy, and others). The evidence was very uncertain due to wide CIs that include important benefit from either the sponsor’s drug or the comparison treatment, and risk of bias. All other results, including real-world DoR and results among chemotherapy-free interval stratifications, were too uncertain to determine any effects due to wide CIs or small sample sizes.
Harms findings versus other second-line treatments: Results from 1 real retrospective observational real-world study demonstrated that the percentage of patients with grade 3 or greater thrombocytopenia and grade 3 or greater anemia was lower among patients receiving lurbinectedin than patients receiving other treatments; although, the precision of the observed effect could not be judged without any between-group effect estimates. A similar percentage of patients receiving lurbinectedin had febrile neutropenia and grade 3 or greater neutropenia compared to patients receiving other second-line treatments. The committee felt the data presented did not raise any new concerns about the safety profile of lurbinectedin, and the observed events were consistent with what is expected with the drug.
Considerations for a time-limited reimbursement recommendation: pERC discussed that Health Canada has mandated that the sponsor complete a confirmatory trial to confirm the improved clinical benefit as measured by PFS and OS. The LAGOON trial will compare lurbinectedin to irinotecan or topotecan, which are conventional treatments for this setting in Canada. While the study population enrolled in the LAGOON trial is generally aligned with the reimbursement request currently under review, pERC discussed that 1 important difference is the requirement for patients enrolled in the LAGOON trial to have a 30 day or longer chemotherapy-free interval at baseline and no requirement for patients to have stage III or metastatic disease. The end point in the LAGOON trial – including OS, PFS, ORR, DoR, HRQoL, and harms – also align with those deemed most important to patients and clinicians. The sponsor has confirmed that the LAGOON trial results will be filed with CDA-AMC in accordance with the timelines and requirements for a reassessment as described in the Procedures for Reimbursement Reviews. pERC noted that, according to the information provided in the sponsor’s submission, primary completion of the ongoing LAGOON trial is expected in 2027. Acknowledging that the Procedures for Reimbursement Reviews allow for a reassessment request to be submitted by the sponsor within 270 calendar days after the completion date of the phase III trial, pERC strongly encourages the sponsor to file for a reassessment as early as possible after the results of the LAGOON trial become available, to address existing uncertainties.
Clinical value: Based on the preceding considerations, pERC determined there was uncertain clinical value versus other second-line treatments. The sponsor-submitted evidence was associated with methodological limitations that resulted in an inability to confidently draw any conclusions.
Input on unmet clinical need: Based on patient and clinician input, pERC noted a substantial need for alternative second-line treatment options for patients with SCLC who progress on or after platinum-based chemotherapy that prolong survival, stop or delay disease progression, and maintain quality of life with reduced symptoms. Current second-line treatment options are of limited effectiveness and are associated with a substantial risk of side effects or adverse events. This need is particularly important for patients who progress within 3 months of their last platinum dose as they are ineligible for platinum rechallenge in the second line. There is also a need to reduce treatment burden, especially in populations that must travel to receive their therapy.
Severity of the disease: Based on patient and clinician input, pERC noted that relapsing SCLC is a serious life-threatening disease with a median survival of 1 to 8 months.
Availability of treatment options: pERC considered input from clinical experts consulted for this review who indicated that patients are often refractory to currently available second-line treatment options which are associated with common and severe adverse events, are inconvenient for patients (i.e., require frequent visits to clinics and sometimes inpatient admissions for treatment), and brain and bone metastases remain common.
Significant unmet clinical need: pERC determined there was significant unmet clinical need due to poor prognosis, short survival, and substantial impact from the disease on patients and caregivers.
Input on unmet nonclinical need: Patients highlighted distress related to the impact of late-stage diagnosis, worry of progression, and limited treatment options. Currently available second-line treatment options are associated with toxicities leading to treatment withdrawal and lower chances of being able to tolerate subsequent third-line therapies. Further, certain treatments, such as topotecan, require frequent clinic visits. pERC noted that these factors are burdensome to patients and caregivers, and this could be partially addressed by lurbinectedin, which requires less frequent administration. However, in the absence of any HRQoL data, the committee could not firmly conclude that lurbinectedin addresses these unmet needs.
Equity considerations: pERC noted the strong association between SCLC and smoking, and that clinical experts felt this association has led to substantial stigma which can potentially impact patient care and public perception. This may be exacerbated among systemically marginalized and equity deserving populations as the clinical experts noted that tobacco use is disproportionately higher among these populations, potentially contributing to their increased risk of developing this disease. However, pERC felt even if lurbinectedin were recommended for public reimbursement, it is unlikely that stigma associated with increased risk of SCLC among systemically marginalized and equity deserving populations will be addressed as these are broader challenges requiring systemic and policy level interventions.
Health impacts of lurbinectedin versus relevant comparators: Due to the use of naive comparison, it is not possible to determine if any observed differences in PFS or OS are due to the effect of treatment or are instead due to bias or confounding. Consequently, the comparative effectiveness of lurbinectedin and other currently available treatments is highly uncertain.
Cost of lurbinectedin versus relevant comparators: Based on the submitted price for lurbinectedin, which equates to $33,507 per 28 days, it is expected to increase health care system costs if reimbursed by public drug plans. Drug acquisition costs were the primary driver of incremental costs between lurbinectedin and comparators.
Key findings of the economic evaluation: The cost-effectiveness of lurbinectedin compared to topotecan; cyclophosphamide, doxorubicin, and vincristine; RWE; or synthetic treatment arm is uncertain. Based on the evidence reviewed for this submission, there is no robust evidence to suggest that lurbinectedin provides greater health benefits to patients than comparators. If lurbinectedin is not expected to provide clinical benefits beyond that of comparators, then the total cost of lurbinectedin to health care systems should not exceed that of any comparator for the treatment of adult patients with stage III or metastatic SCLC. Among the RWE and synthetic control arm basket comparators, cisplatin and etoposide was the least costly regimen.
Certainty of the evidence: Based on the single-arm Study B-005, CDA-AMC concluded that PFS and OS could not be interpreted due to lack of direct evidence to inform the relative efficacy of lurbinectedin versus comparators. Additionally, a number of internal and external validity concerns were identified by CDA-AMC, which precludes use of the ITC or real-world observational study to inform decision-making for lurbinectedin versus comparators.
Anticipated budget impact: CDA-AMC estimated that by year 3 of reimbursement, 1,352 patients would be eligible for lurbinectedin, of whom 724 are expected to receive lurbinectedin. The estimated incremental budget impact of reimbursing lurbinectedin is predicted to be approximately $98.8 million over the first 3 years, with an expected expenditure of $107.3 million on lurbinectedin. The actual budget impact of reimbursing lurbinectedin will depend on the number of treatment cycles received with lurbinectedin, the number of people eligible for treatment, and the uptake of lurbinectedin.
To make its recommendation, the committee considered the following information (links to the full documents for the review can be found on the project webpage):
the CDA-AMC review of the clinical and pharmacoeconomic evidence submitted by the sponsor, as well as relevant ethical issues related to lurbinectedin (refer to the Main Report and Supplemental Material documents)
the sponsor’s comments on the draft report and the responses from CDA-AMC
patients' perspectives gathered by patient groups, a submission from Lung Cancer Canada, Lung Health Foundation, and Canadian Cancer Survivor Network (refer to the Patient and Clinician Group Input document)
input from 2 clinician groups, Ontario Health (Cancer Care Ontario) Lung and Thoracic Cancer Drug Advisory Committee and Lung Cancer Canada – Medical Advisory Committee (refer to the Patient and Clinician Group Input document)
input from public drug programs that participate in the reimbursement review process (refer to the Supplemental Material document)
input from 2 clinical experts with expertise in the management of SCLC consulted by CDA-AMC.
Dr. Catherine Moltzan (Chair), Dr. Kelvin Chan (Vice-Chair), Paul Agbulu, Dr. Phillip Blanchette, Dr. Matthew Cheung, Dr. Michael Crump, Annette Cyr, Dr. Jennifer Fishman, Dr. Jason Hart, Terry Hawrysh, Dr. Yoo-Joung Ko, Dr. Aly-Khan Lalani, Amy Peasgood, Dr. Anca Prica, Dr. Michael Raphael, Dr. Adam Raymakers, Dr. Patricia Tang, Dr. Pierre Villeneuve, and Danica Wasney.
Meeting date: February 11, 2026
Regrets: One expert committee member did not attend.
Conflicts of interest: None
ISSN: 2563-6596
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