Single Technology Appraisal Alectinib for untreated anaplastic lymphoma kinase positive ...

685 Pages·2017·11.31 MB·English

by  Jeremy Powell

Single Technology Appraisal

Alectinib for untreated anaplastic
lymphoma kinase positive advanced non-
small-cell lung cancer [ID925]

Committee Papers
© National Institute for Health and Care Excellence 2018. All rights reserved. See Notice of Rights. The content
in this publication is owned by multiple parties and may not be re-used without the permission of the relevant
copyright owner.
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE

SINGLE TECHNOLOGY APPRAISAL

Alectinib for untreated anaplastic lymphoma kinase positive advanced non-
small-cell lung cancer [ID925]

The final scope and matrix of consultees and commentators are available on the
NICE website for this appraisal.

Contents:

1. Pre-Meeting Briefing

2. Company submission from Roche

3. Clarification letters
 NICE request to the company for clarification on their submission
 Company response to NICE’s request for clarification

4. Patient group, professional group and NHS organisation submission
from:
 British Thoracic Oncology Group
 British Thoracic Society
 NHS England
 Roy Castle Lung Cancer Foundation

5. Expert statements from:
 Alastair Greystoke, clinical expert, nominated by Pfizer
 Riyaz Shah, clinical expert, nominated by Roche
 Lesley Holland, patient expert, nominated by National Lung Cancer
Forum for Nurses

6. Evidence Review Group report prepared by BMJ Technology Assessment
Group (BMJ-TAG)

7. Evidence Review Group report – factual accuracy check

8. Evidence Review Group report – erratum

9. Evidence Review Group report – addendum

10. Evidence Review Group – second erratum

Any information supplied to NICE which has been marked as confidential has been
redacted
© National Institute for Health and Care Excellence 2018. All rights reserved. See Notice of Rights. The content
in this publication is owned by multiple parties and may not be re-used without the permission of the relevant
copyright owner.
Pre-meeting briefing
Alectinib for untreated anaplastic lymphoma
kinase-positive advanced non-small cell
lung cancer [ID925]
This slide set is the pre-meeting briefing for this appraisal. It has been
prepared by the technical team with input from the committee lead team
and the committee chair. It is sent to the appraisal committee before the
committee meeting as part of the committee papers. It summarises:
• the key evidence and views submitted by the company, the consultees
and their nominated clinical experts and patient experts and
• the Evidence Review Group (ERG) report
It highlights key issues for discussion at the first appraisal committee
meeting and should be read with the full supporting documents for this
appraisal
Please note that this document includes information from the ERG before
the company has checked the ERG report for factual inaccuracies
The lead team may use, or amend, some of these slides for their
presentation at the Committee meeting 1
Key issues
Clinical effectiveness:
• Can conclusions be drawn about overall survival given the immaturity of the data?
• What are the committee’s conclusions on the ALEX clinical trial that compared
alectinib with crizotinib in terms of quality, risk of bias and generalisability given:
– Different measurements of progression-free survival and CNS- progression-free
survival (investigator, IRC RECIST or IRC RECIST & CNS-RECIST)?
– Treatment of asymptomatic disease after progression?
– Missing data on subsequent treatment distribution?
Cost effectiveness:
• Are assumptions about post-progression subsequent treatment distribution plausible?
• Company chose 18 month Kaplan-Meier data cut-off point for progression-free
survival extrapolation  is this appropriate?
• Company extrapolated overall survival using exponential distribution, ERG preferred
KM + exponential tail  which is most appropriate?
• Management of CNS events: in company base-case 100% patients have stereotactic
radiosurgery (SRS) & steroids; in company scenario analysis 23% have SRS, 77%
have whole brain radiotherapy (WBRT) & all have steroids  are either appropriate?
2
Non-small cell lung cancer (NSCLC)
• Usually no early signs, presents in advanced stages III/IV (75%)
• Symptoms include cough, breathlessness, blood in sputum, weight loss
• 2 histological types: non-small-cell (85–90%) and small cell
• Approximately 40% to 50% of patients with NSCLC develop central
nervous system (CNS) metastases which are associated with poor
median survival (4 to 9 months with chemotherapy, 2 months if untreated)
• Anaplastic lymphoma kinase (ALK) fusion genes are chromosomal
alterations believed to be involved in tumour growth, and occur most
commonly in tumours with adenocarcinoma histology (non-squamous)
• ~5% people with advanced NSCLC have ALK mutation (1170 people in
England)
ERG comment:
• ALK variant: younger, female, less associated with smoking history
• As a result, may not be picked up by ‘high risk’ screening programs
3
Patient perspectives
• Submission from Roy Castle Lung Cancer Foundation
• Non-small cell lung cancer (NSCLC) is a disease with
no cure that can lead to physical and psychological
distress
• Anaplastic Lymphoma Kinase (ALK) gene
rearrangement found in a very few lung cancer
patients
• New target therapies offer much better therapy
options for these patients
• Compared with Crizotinib, Alectinib has superior
efficacy and lower toxicity
4
Clinician perspectives
• Submissions: British Thoracic Oncology Group, and 3 clinical experts
• “Brain metastases are uniquely difficult to treat and palliate”
• ALEX trial:
– Only 1% UK population (45% Asian)
– Sample may be healthier than UK  may over-estimate survival gains
– But survival gains expected given brain disease control
• Compared to Crizotinib, Alectinib:
– Is better tolerated (so reduced resources)
– Has better intracranial disease control and progression-free survival
– Enables better quality of life
– Leads to fewer neurological investigations and interventions
– “Paradigm shift”
• Stopping rule: “when radiological and clinical progression on treatment”
• Same oral administration as Crizotinib – minimal new resources/ education
5
Current treatment for advanced NSCLC
ALK-positive ALK status unknown
Crizotinib Ceritinib Pemetrexed in combination
Alectinib?
(TA406) (TA500) with cisplatin (TA181)
ALK-positive status confirmed
Ceritinib (TA395) Crizotinib (TA422) Crizotinib (TA422)
Chemotherapy
Best supportive care
ERG comment:
• Treatment pathway in line with NICE pathway for NSCLC
• Ceritinib now available for first line use (TA500)  uncertainty about effect on
treatment pathway
6
Alectinib (Alecensa)
Roche
Mechanism of action 2nd generation tyrosine kinase inhibitor (TKI)
Marketing authorisation Alectinib as a monotherapy is indicated for
the first line treatment of adult patients with
anaplastic lymphoma kinase (ALK)-positive
advanced non-small cell lung cancer
(NSCLC).
Administration Oral
Dose 600 mg (4x 150 mg capsules) twice daily
Duration of treatment Continued until disease progression or
unacceptable toxicity
Cost (list price) £5,032 per 224 capsule pack (28 day supply)
Patient access scheme has been accepted
by Department of Health. This provides a
simple discount to list price.
7
Decision problem
Scope Company?
Population Adults with untreated anaplastic
lymphoma kinase-positive (ALK-
✓
positive) advanced non-small-cell
lung cancer (NSCLC)
Intervention Alectinib ✓
Comparators Crizotinib ✓
Outcomes • Overall survival
• Progression-free survival
• Response rates ✓
• Adverse effects of treatment
• Health-related quality of life
8