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BIBF 1120 for advanced and/or metastatic non-small cell lung cancer – second line

Source agency:

NHSC

Date of Submission:

15/12/2009

Date of Printing:

05/02/2012

Disclaimer:

This report is work in progress and should not be used for external distribution without permission from the originating agency. Users should be aware that reports are based on information available at the time of research and often on a limited literature search.

Technology, Company & Licensing

Technology name:

BIBF 1120

Technology - description:

BIBF 1120 is an oral antiangiogenic inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR). Inhibition of these growth factors limits the supply of oxygen and nutrients to cancer cells by reducing vascularisation of tumours, thereby suppressing tumour growth. BIBF 1120 is orally administered in combination with pemetrexed (Alimta) or docetaxel (Taxotere) and is being trialled at doses of 150-250mg twice daily.
BIBF 1120 is also in phase III clinical trials for advanced ovarian cancer and phase II clinical trials for colorectal cancer, renal cell carcinoma, and hepatocellular carcinoma.

Company or developer:

Boehringer Ingelheim

Reason for database entry:

BIBF 1120 is the first antiangiogenic agent to act on three different types of receptors involved in tumour angiogenesis. BIBF 1120 may, in combination with standard chemotherapy, prolong the disease control of patients with NSCLC who have failed one prior line of chemotherapy. In addition, the combination of BIBF 1120 with docetaxel would provide a treatment option for patients with squamous cell lung cancer, for which pemetrexed is not licensed.

Technology - stage in early warning process:

Assessment complete

Technology - stage of development:

Investigational - phase III

Licensing, reimbursement and other approval:

In phase III clinical trials.

Technology - type(s):

Drug

Technology - use(s):

Combination

Patient Indication & Setting

Patient indications:

Non-small cell lung cancer (NSCLC): advanced and/or metastatic stage IIIB/IV or recurrent – second line; in combination with pemetrexed (Alimta) or docetaxel (Taxotere) after failure of prior chemotherapy.

Disease description and associated mortality and morbidity:

 

Number of Patients:

Lung cancer is the most common cause of cancer-related death in men, and the second most common cause of cancer-related death after breast cancer in women. In 2007, there were 35,016 new cases of lung cancer in England and Wales(1)(2), (an incidence of around 64 cases per 100,000 population) and 29,574 registered deaths (an incidence of around 54 deaths per 100,000 population)(3). In England and Wales lung cancer has a one-year survival rate of 25% and a five-year survival rate of 7%(4).
NSCLC accounts for approximately 80% of all lung cancers, with the main types being squamous cell carcinoma, adenocarcinoma and large cell carcinoma (5). Approximately 75% of newly diagnosed NSCLC patients have advanced (stage III or IV) disease in England and Wales (approximately 21,010 patients)(6) which has five-year survival rates of less than 1%(7).
In late stage NSCLC, treatment offers the patient the possibility of symptom relief, improved disease control, better quality of life and increased survival. However, not all patients with advanced disease are fit enough to receive systemic treatment (8). Approximately 25% of patients with advanced NSCLC receive first-line chemotherapy and around 20-40% of these (1,050-2,100 patients) may be eligible to receive second-line therapy(9).

Technology - specialities(s):

Oncology & radiotherapy

Technology - setting(s):

Community and primary care, General hospital and ambulatory care

Setting - further information:

 

Impact

Alternative and/or complementary technology:

Additive or complementary technology

Current Technology:

Second line therapy options for NSCLC include:
•Docetaxel (Taxotere) - a mitosis inhibitor.
•Erlotinib (Tarceva) - an epidermal growth factor receptor antagonist (not licensed after failure of second-line docetaxel therapy(10)).
•Pemetrexed (Alimta) - a thymidylate synthase and dihydrofolate reductase inhibitor - licensed but not currently recommended by NICE(11)(not licensed for predominantly squamous cell histology).

There is currently no approved therapy for NSCLC patients who have progressed after previous cytotoxic chemotherapy or who have developed resistance after initial clinical benefit.

Health Impact:

Reduced mortality or increased length of survival (speculative).

Diffusion:

Cost, infrastructure and economic consequences:

The cost of BIBF 1120 is not yet known.

Ethical, social, legal, political and cultural impact:

 

Evidence & Policy

Clinical evidence and safety:

Trial: Relapsed advanced NSCLC; phase II.
Sponsor: Boehringer Ingelheim.
Status: Trial complete and published in abstract.
Source of information: Abstract(12).
Location: Germany.
Design: Randomised, uncontrolled.
Participants and schedule: n=73; adults; ECOG score 0-2, relapsed stage IIIB/IV NSCLC, after first or second line chemotherapy. Initially randomised to BIBF 1120 250mg or 150mg twice daily. In the event of dose limiting toxicity, single dose reduction to open label treatment with 150mg or 100mg twice daily.
Follow-up: Until disease progression.
Primary outcome/s: PFS, OTR.
Key results: Median PFS 1.6 months (all patients); no significant difference between treatment arms; stable disease 48% without objective tumour response. ECOG score 0 or 1 (n= 57): median PFS 2.9 months; 3 and 5 month PFS rate 46% and 31%; no significant difference between treatment arms; stable disease 59%.
Adverse effects (AEs): Dose limiting grade 3 and 4 toxicities: 27% and 2.8% for 250mg and 150 mg twice daily respectively (p=0.006). Grade 1 or 2 AEs: nausea (41%), diarrhoea (41%), vomiting (33%), fatigue (29%), abdominal pain (22%). Grade 3 and 4 toxicities: nausea (8%), diarrhoea (7%), vomiting (4%), abdominal pain (4%), AST (aspartate aminotransferase) and/or ALT (alanine aminotransferase) elevations (5.4%).

Economic evaluation:

 

Ongoing research:

Trial: LUME-Lung 1 (1199.13); BIBF1120 and docetaxel vs placebo and docetaxel; phase III.
Sponsor: Boehringer Ingelheim.
Status: Ongoing.
Source of information: Trial registry(13).
Location: EU (including UK), USA, Canada, and other countries.
Design: Randomised, controlled.
Participants and schedule: n=1,300 (planned); adults; advanced (stage IIIB or IV) or recurrent. NSCLC; progressed after first line chemotherapy. Randomised to BIBF 1120 200mg twice daily and docetaxel, or placebo and docetaxel until disease progression or withdrawal criteria are met.
Follow-up: Until disease progression, loss to follow-up or death.
Primary outcome: Progression free survival (PFS)
Secondary outcomes: Overall survival, adverse events (AEs), tumour response, health related quality of life (HRQL).
Expected reporting date: Q2 2011.

Trial: LUME-Lung 2 (1199.14); BIBF1120 and pemetrexed vs placebo and pemetrexed; phase III
Sponsor: Boehringer Ingelheim.
Status: Ongoing.
Source of information: Trial registry (14) .
Location: EU (excluding UK), USA, and other countries.
Design: Randomised, controlled.
Participants and schedule: n=1,300 (planned); adults; advanced (stage IIIB or IV) or recurrent. NSCLC; progressed after first line chemotherapy. Randomised to BIBF 1120 200mg twice daily and pemetrexed or placebo and pemetrexed until disease progression or withdrawal criteria are met.
Follow-up: Until disease progression, loss to follow-up or death.
Primary outcome: PFS.
Secondary outcomes: Overall survival, AEs, tumour response, HRQL.
Expected reporting date: Q4 2011.

Ongoing or planned HTA:

 

Web link:

http://www.nhsc-healthhorizons.org.uk/outputs/specialties/

References and sources:

(1)Cancer Research UK. http://info.cancerresearchuk.org/cancerstats/types/lung/mortality/index.htm Accessed 18November 2009.
(2)Welsh Cancer Intelligence and Surveillance Unit. Cancer incidence in Wales, 2003-2007: http://www.wales.nhs.uk/sites3/docmetadata.cfm?orgid=242&id=110389 Accessed 18 November 2009.
(3)Cancer Research UK. http://info.cancerresearchuk.org/cancerstats/types/lung/mortality Accessed 23 October 2008.
(4)National Institute for Health and Clinical Excellence. Pemetrexed for maintenance treatment following first line chemotherapy for non-small cell lung cancer. Final scope of technology appraisal in development.London: NICE. June 2009.
(5)National Institute for Health and Clinical Excellence. Lung cancer: the diagnosis and treatment of lung cancer. Clinical guideline CG024. London: NICE; February 2005.
(6)Liverpool Reviews and Implementation Group, ERG Report – Pemetrexed for the treatment of relapsed non- small cell lung cancer. London: National Institute for Clinical Excellence. September 2006.
(7)National Collaborating Centre for Acute Care. The diagnosis and treatment of lung cancer: methods, evidence and guidance. London: National Collaborating Centre for Acute Care. February 2005.
(8)Coleman M, Rachet B, Woods L et al. Trends in socio-economic inequalities in cancer survival in England and Wales up to 2001. British Journal of Cancer 2004; 90(7): 1367-73.
(9)National Institute for Health and Clinical Excellence. Pemetrexed for maintenance treatment following first line chemotherapy for non-small cell lung cancer. Final scope of technology appraisal in development.London: NICE. June 2009.
(10)National Institute for Health and Clinical Excellence. Erlotinib for the treatment of non-small cell lung cancer. Technology appraisal TA162. London: NICE; November 2008.
(11)National Institute for Health and Clinical Excellence. Pemetrexed for the first line treatment of non-small cell lung cancer. Technology appraisal TA181. London: NICE; September 2009.
(12)Pawel J, Kaiser R, Eschbach C et al. A double blind phase II study of BIBF 1120 in patients suffering from relapsed advanced non-small cell lung cancer (NSCLC). 2007 ASCO Annual Meeting Proceedings. Journal of Clinical Oncology 2007; 25 (18S): 7635.
(13)ClinicalTrials.gov. LUME-Lung 1: BIBF 1120 plus docetaxel as compared to placebo plus docetaxel in 2nd line non small cell lung cancer. http://clinicaltrials.gov/ct2/results?term=NCT00805194 Accessed 18 November 2009.
(14)ClinicalTrial.gov. Lume Lung 2: BIBF 1120 plus pemetrexed compared to placebo plus pemetrexed in 2nd line nonsquamous NSCLC. http://clinicaltrials.gov/ct2/results?term=NCT00806819 Accessed 18 November 2009.

Notes: