ALUNBRIG is indicated as monotherapy for the treatment of adult patients with:1
- anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (aNSCLC) previously not treated with an ALK inhibitor
- ALK+ aNSCLC previously treated with crizotinib
Funded TKI options in ALK+ aNSCLC in England
(according to NICE/ NHS England Blueteq criteria)
ALUNBRIG is funded on the NHS in England in first- and second‑line (post‑crizotinib) settings for ALK+ aNSCLC2,3
NICE TA6702
Brigatinib is recommended, within its marketing authorisation, as an option for treating anaplastic lymphoma kinase (ALK)‑positive advanced non‑small‑cell lung cancer (NSCLC) that has not been previously treated with an ALK inhibitor in adults. It is recommended only if the company provides brigatinib according to the commercial arrangement.
NICE TA5713
Brigatinib is recommended, within its marketing authorisation, for treating anaplastic lymphoma kinase (ALK)‑positive advanced non‑small‑cell lung cancer (NSCLC) in adults who have already had crizotinib. It is recommended only if the company provides it according to the commercial arrangement.
According to NHS England Blueteq criteria, ALUNBRIG may be used where the patient has:4
- histological or cytological evidence of NSCLC that carries an ALK rearrangement based on a validated test
OR
- there is documented agreement by the lung MDT that the radiological appearances are in keeping with locally advanced or metastatic NSCLC
AND
- there is an informative circulating free DNA test result confirming the presence of an activating ALK rearrangement
ALUNBRIG is funded on the NHS in first- and second‑line (post crizotinib) settings for ALK+ aNSCLC.2,3
Summary of funded treatment options in England, based on NICE technology appraisals, the Cancer Drugs Fund and NHS England Blueteq eligibility criteria.2,3,4,6*
In the case of intolerance to a first-line ALK inhibitor patients can switch to another solely as a consequence of dose-limiting toxicity and in the clear absence of disease progression. Refer to Blueteq criteria for the permitted timeframe for individual ALK inhibitors.4
Following first-line crizotinib, patients can be switched from ceritinib to ALUNBRIG or vice versa within 3 months of starting the first agent, solely as a consequence of dose-limiting toxicity and in the clear absence of disease progression.4
*Please refer to the NICE website and NHS England Blueteq eligibility criteria for further guidance on recommended treatment options and treatment options after progression on all available TKIs.
†Per NHS England Treatment Eligibility Criteria, lorlatinib is funded in this setting through NHS England, as reflected in the Blueteq criteria.4
‡Treatment options after TKIs include chemotherapy and best supportive care, refer to NICE treatment pathway for full information.5
A retrospective chart review study of subsequent treatments following 1L ALUNBRIG in the ALTA1L trial
Brigatinib-5010, a retrospective, non‑interventional, international, multi‑site chart review study investigated the real‑world treatment patterns and outcomes of subsequent treatments following discontinuation of 1L ALUNBRIG in the ALTA‑1L trial.7
In this study, second-line lorlatinib after first-line ALUNBRIG resulted in a median rwPFS2§ of more than 6 years (74.7 months (95% CI: 25.9-NR)).7
Click the tabs below to see more.
§rwPFS2 was defined as time from randomisation in ALTA-1L to disease progression on second-line treatment or death from any cause among patients who initiated subsequent systemic anticancer treatments.7
Patients7
- 20 sites enrolled patients across 10 countries
- 48 patients were enrolled
- The majority of patients were female (54.2% (n=26)), identified as Asian (54.2% (n=26)) and were never smokers (62.5% (n=30))
- Median follow-up was 12.4 months
- The most common reason for 1L ALUNBRIG discontinuation was PD (70.9% (n=34))
- Median time from index date to start of 2L treatment was 4.0 (95% CI: 3.0-9.0) days
Study outcomes7
- rwTTD: time from initiation to discontinuation of 2L treatment for any reason
- rwPFS: time elapsed from initiation of 2L treatment to disease progression or death
- rwPFS2: time from randomisation in ALTA-1L trial to first documented disease progression on 2L treatment or death due to any cause among those patients who initiated subsequent systemic anticancer treatments
- OS: time from date of randomisation in the ALTA-1L trial until date of death
Study limitations7
- Subset of included sites and patients may not be representative of all sites and overall cohort of patients enrolled in ALTA-1L
- Due to small sample size, KM estimates of median require cautious interpretation, particularly given the wide confidence intervals: study was not powered to detect differences between subgroups
- The timing between patients discontinuing 1L ALUNBRIG and receiving subsequent systemic anticancer therapies may have differed within the cohort of patients included in the study
- Use of retrospective chart review data may be associated with systematic under-reporting of information
83.3% (40/48) of patients started subsequent systemic anticancer therapy after discontinuation of 1L ALUNBRIG.7
- Most common first subsequent therapies were ALK TKIs (used in 75.0% (30/40) of patients)7
- Lorlatinib was the most common targeted therapy (used in 53.3% (16/30) of patients)
| First subsequent systemic anticancer therapy | n (%) |
|---|---|
| Alectinib | 7 (17.5) |
| Alectinib + chemotherapy | 1 (2.5) |
| Chemotherapy | 9 (22.5) |
| Chemotherapy + immunotherapy | 1 (2.5) |
| Crizotinib | 6 (15.0) |
| Lorlatinib | 15 (37.5) |
| Lorlatinib + ramucirumab|| | 1 (2.5) |
| Total | 40 (100) |
||Please note, lorlatinib + ramucirumab is an off-label combination.
Refer to individual ALK TKI SmPCs for information on indication and safety profile.
Patients treated with 1L ALUNBRIG, followed by subsequent ALK TKIs (including lorlatinib), experienced prolonged clinical benefits.7
Lorlatinib was the most common first subsequent therapy after ALUNBRIG.7
- Median rwPFS2 of more than 6 years was seen with second-line lorlatinib after first‑line ALUNBRIG
- The 3-year rwPFS2 was 73.3% with second-line lorlatinib after first‑line ALUNBRIG
Due to small sample size, KM estimates of median require cautious interpretation, particularly given the wide confidence intervals; study was not powered to detect differences between subgroups
¶Discontinuation of 2L ALK TKIs was reported for 14 (46.7%) patients and 2L lorlatinib was reported for 5 (31.3%) patients.
Figures adapted from Delmonte A et al, 20247
Disease control rate
Real-world overall response rate (rwORR)
(in patients with reported values)
- 2L ALK TKIs: 33.3% (95% Cl: 15.6, 55.3)
- 2L lorlatinib: 30.8% (95% Cl: 9.1, 61.4)
Real-world disase control rate (rwDCR)
(in patients with reported values)
- 2L ALK TKIs: 70.8% (95% Cl: 48.9, 87.4)
- 2L lorlatinib: 76.9% (95% Cl: 46.2, 95.0)
**The 2L ALK TKI cohort (n=30) includes those patients treated with 2L lorlatinib (n=16).
Overview of adverse events of special interest after frontline brigatinib
aAESIs were AEs that occurred frequently in ALK TKI clinical trials and were assessed from the time of ALUNBRIG discontinuation through initiation of 2L treatment until the end of follow-up or death. AESIs included alanine aminotransferase increase, anaemia, aspartate aminotransferase increase, blood bilirubin increase, cognitive/mood effects, constipation, cough, creatine phosphokinase increase, diarrhoea, gamma-glutamyl transferase increase, hypercholesterolaemia, hypertension, hypertriglyceridaemia, increased weight, lipase level increase, myalgia, nausea, peripheral oedema, peripheral neuropathy, vision disorder, and vomiting.
Click below to access the associated expert opinion video where Dr Sharmistha Ghosh discusses this data as one of the study authors. Dr Ghosh focuses on the treatment outcomes associated with second-line lorlatinib post first-line ALUNBRIG.
ALK, anaplastic lymphoma kinase; DNA, deoxyribonucleic acid; MDT, multidisciplinary team; NSCLC, non‑small cell lung cancer; 1L, first line; 2L, second line; CI, confidence interval; NR, not reached; OS, overall survival; PD, progressive disease; rwPFS, real‑world progression‑free survival; rwPFS2, real‑world progression‑free survival 2; rwTTD, real-world time to treatment discontinuation; TTD, time to treatment discontinuation; rwDCR, real‑world disease control rate; rwORR, real‑world objective response rate; SD, stable disease; AESI, adverse event of special interest; TKI, tyrosine kinase inhibitor.
1. ALUNBRIG (brigatinib) Summary of Product Characteristics. Available at: medicines.org.uk. Accessed June 2026; 2. National Institute for Health and Care Excellence (NICE). Technology appraisal guidance 670. Brigatinib for ALK‑positive advanced non-small-cell lung cancer that has not been previously treated with an ALK inhibitor, January 2021. Available at: nice.org.uk. Accessed June 2026; 3. National Institute for Health and Care Excellence (NICE). Technology appraisal guidance 571. Brigatinib for treating ALK-positive advanced non‑small‑cell lung cancer after crizotinib, March 2019. Available at: nice.org.uk. Accessed June 2026; 4. NHS England. National Cancer Drugs Fund list. Available at: england.nhs.uk. Accessed June 2026; 5. National Institute for Health and Care Excellence (NICE). NICE guideline 122. Systemic anti-cancer therapy for advanced non-small-cell lung cancer: treatment options, March 2019 (updated March 2024). Available at: nice.org.uk. Accessed June 2026; 6. National Institute for Health and Care Excellence (NICE). Technology appraisal guidance 1103. Lorlatinib for ALK-positive advanced non-small-cell lung cancer that has not been treated with an ALK inhibitor. October 2025. Available at: nice.org.uk. Accessed June 2026; 7. Ahn M, Delmonte A et al. Real-world treatment patterns and subsequent treatment effectiveness following frontline brigatinib in the ALTA-1L trial. Future Oncol. 2025;21:3935-3945
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