| Information |
Generic Name: |
afatinib
|
| Trade Name: |
Tomtovok |
| Synonym: |
BIBW 2992 |
| Entry Type: |
New molecular entity |
| |
| Developmental Status |
| UK: |
Pre-registration (Filed) |
| EU: |
Pre-registration (Filed) |
| US: |
Pre-registration (Filed) |
| UK launch Plans: |
Available only to registered users |
| Actual UK launch date: |
|
| Comments |
Jan 13: Filed in the US and granted Priority Review for the treatment of patients with locally advanced or metastatic NSCLC with an EGFR mutation as detected by an FDA-approved test. The FDA decision on approval is expected 3Q 2013 [11]
24/01/2013 13:32:57 |
Sep 12: The company has initiated an open-label, US multi-centre expanded access program (EAP) for afatinib for eligible patients with locally advanced or metastatic NSCLC who have an EGFR mutation (clinical trial identifier NCT01649284). Patients not previously treated with an EGFR targeted therapy as well as those previously treated with these agents may be eligible [9].
23/09/2012 21:48:29 |
Sep 12: Filed in the EU for approval as a treatment for patients with EGFR mutation positive NSCLC, based on results of the PIII LUX-Lung 3 study [8].
20/09/2012 11:27:46 |
EU filing anticipated Q3 2012 [6]
18/05/2012 12:12:27 |
EU submission anticipated Q1 2012 (2)
12/08/2009 11:35:35 |
Aug 09: PIII study as 1st line treatment in patients with EGFR mutations started [1].
11/08/2009 21:11:41 |
| |
| Trial or other data |
May 13: NCT01853826 is an open label safety trial of afatinib in 468 treatment-naive or chemotherapy pre-treated patients (EGFR-TKI treatment naïve) with locally advanced or metastatic NSCLC harbouring EGFR mutation(s). The study starts Jun 13 and is due to complete Jul 15 [13]
17/05/2013 10:04:59 |
NCT01121393 LUX lung 6: Afatinib vs gemcitabine-cisplatin in 1st line stage IIIB or stage IV adenocarcinoma NSCLC habouring EGFR mutation. Started Apr 10 and due to complete Apr 14 [12]
12/03/2013 10:59:21 |
Oct 12: Patient-reported health-related outcomes, secondary endpoints of LUX-Lung 3 study, were reported at ESMO 2012. Three lung cancer were analyzed using the EORTC QoL questionnaire for lung cancer (QLQ-LC13). A higher proportion of afatinib-treated patients had ≥10 point improvement in cough (67% vs. 60%; p=0.2444), dyspnea (64% vs. 50%; p=0.0103) and pain (59% vs. 48%; p=0.0513) vs those treated with chemotherapy. Patients on afatinib also reported a delay in the worsening of their lung cancer-related symptoms - cough (HR=0.60; p=0.0072) and dyspnea (HR=0.68; p=0.0145). The time to deterioration of pain was not significant between the treatment arms (HR=0.82; p=0.1913). Afatinib patients experienced improvements in their global health-related QoL and physical, cognitive and role functioning compared to chemotherapy (p<0.05). Afatinib-treated patients reported worse scores for diarrhoea, sore mouth and dysphagia; patients treated with cisplatin/pemetrexed reported worse scores for fatigue, nausea and vomiting [8]
08/10/2012 09:19:46 |
Jun 12: Results from the PIII LUX-Lung 3 study reported at ASCO. LUX-Lung 3 is an open-label RCT comparing afatinib vs pemetrexed + cisplatin, as first-line treatment in 345 patients with stage IIIb or IV NSCLC harboring an EGFR mutation. PFS was 11.1 vs 6.9 months, respectively. In patients with the most common EGFR mutations (del19 and L858R, accounting for 90% of all EGFR mutations) PFS was 13.6 vs 6.9 months, respectively. More patients on afatinib experienced improvement of symptoms such as dyspnea, cough and chest pain and afatinib also delayed the onset of these symptoms. Diarrhoea (95%), rash (62%), and paronychia (57%) were the most common drug-related adverse events observed in the afatinib treatment arm [7].
05/06/2012 22:11:16 |
Mar 12: LUX-Lung 2 published early online in Lamcet Oncology (26 Mar). It assessed the efficacy of afatinib in pts with lung adenocarcinoma (stage IIIb with pleural effusion or stage IV) & EGFR mutations who had no more than one previous chemotherapy regimen for advanced disease, an ECOG performance status of 0—2, & no previous treatment with EGFR tyrosine-kinase inhibitors. A total of 129 pts were treated with afatinib, 99 with a starting dose of 50 mg & 30 with a starting dose of 40 mg. The aim of the study was to establish whether tolerability could be improved with retention of anti-tumour activity. The primary endpoint was the proportion of patients with a confirmed objective response (complete response or partial response), on the basis of Response Evaluation Criteria in Solid Tumors 1.0 (independent review). Similar proportions of pts had an objective response when analysed by starting dose (18 [60%] of 30 pts at 40 mg vs. 61 [62%] of 99 patients at 50 mg). 79 (61%) of 129 pts had an objective response (two complete responses, 77 partial responses). 70 (66%) of the 106 pts with the two common activating EGFR mutations (deletion 19 or L858R) had an objective response, as did nine (39%) of 23 pts with less common mutations. Of the two most common adverse events (diarrhoea & rash or acne), grade 3 events were more common in pts receiving a 50 mg starting dose (22 [22%] of 99 pts for diarrhoea & 28 [28%] of 99 pts for rash or acne) than they were in those receiving a 40 mg starting dose (two [7%] of 30 pts for both diarrhoea and rash or acne); treatment-related serious adverse events were also less common in pts receiving a 40 mg starting dose (two of 30 pts vs. 14 of 99 pts). One possibly drug-related death (interstitial lung disease) was reported [5].
27/03/2012 10:44:10 |
LUX-Lung 2 is a PII trial evaluating afatinib in NSCLC pts with EGFR mutations, either chemotherapy naïve or after one line of chemotherapy. In two further ongoing global PIII trials, LUX-Lung 3 & LUX-Lung 6, the efficacy & safety profile of afatinib is compared to standard chemotherapy for first-line treatment of NSCLC pts with EGFR mutations in different geographical regions [4].
04/07/2011 12:14:57 |
In May 09, Boehringer Ingelheim entered into an agreement with the Manchester, UK-based company DxS to provide a companion diagnostic test kit for BIBW 2992 to identify mutations of the EGFR in patients with NSCLC [3].
02/09/2009 10:18:54 |
Preliminary data from the Phase II LUX-Lung 2 trial of NSCLC patients with an EGFR mutation showed a response rate of 63% and a disease control rate of 97% in 38 evaluable first-line patients. The most commonly (> 5%) adverse events were Grade 3 and included diarrhoea, skin-related adverse events and mouth ulcerations. Comparable response rates (66%) and disease control rates (97%) were observed in the second-line setting [3].
02/09/2009 10:18:42 |
LUX-LUNG 3: PIII trial in 1st line NSCLC pts with EGFR+ve mutation, compared to chemotherapy. Estimated 330 pts. Trial to start July 2009. (2)
12/08/2009 11:36:41 |
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| Evidence Based Evaluations |
| NICE scope |
http://www.nice.org.uk/nicemedia/live/14070/63446/63446.pdf |
| NHSC |
http://www.nhsc-healthhorizons.org.uk/files/downloads/1072/1578.4e1951168d9773e35cb77ddd876d6ef8.pdf |
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| References |
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| Available only to registered users |
Uk Medicines Information 