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How should the BIBW2992 page be modified? (Nov 2010)

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Hello. First attempt at engaging with wikipedia. I am creating a 'talk page' for BIBW-2992 to allow any changes or additions to that page (a stub) to be modified. I am motivated to collect up to date information on the availability and accessibility patients have to this new drug. Thank you for your time and advice on what I should do next! :-) Theskepticaloptimist (talk) 11:31, 11 November 2010 (UTC)[reply]

Hi Theskepticaloptimist! Thanks your help here. First of all, please sign your comments on talk pages (as you'vre done here) but not your contributions to articles.
Since the drug has now a name (an International Nonproprietary Name, I suppose), the article should be moved there. I don't want to move it away (not to confuse you) – if you want to do it, click the arrow to the left of the search box, click "Move", then type the new name (Afatinib) and a reason like "International Nonproprietary Name", and click "Move page".
A list of desired sections for articles about drugs, as well as further information about this type of article, is at Wikipedia:WikiProject Pharmacology/Style guide. Some of the sections won't apply yet because not all information is available at this point of development. Just leave out these sections, they can be added later. I'll watch your contributions to this article and talk page and try to answer any questions you might have. I'll also do some cleanup (like formatting references) if you don't object.
Finally: Please fill in the "Summary" when you edit; this is of tremendous help for your fellow editors. Happy editing! --ἀνυπόδητος (talk) 13:39, 11 November 2010 (UTC)[reply]

Hm. OK. Thank you for your encouragement Anypodetos. Without it I might not have bothered to engage again! Out of curiosity, and based on your advice alone, I will attempt to 'move' the article as you suggest. Feel free to alter my posts as you see fit (formatting or otherwise). I will start a talk page on the new 'moved' page to continue this conversation if it doesn't carry over automatically. Theskepticaloptimist (talk) 22:06, 12 November 2010 (UTC)[reply]

I have double checked and yes Afatinib has been listed by the WHO for inclusion as an INN. (http://www.whocc.no/atc/lists_of_new_atc_ddds_and_altera/new_atc/) I will have to wait until 4 days and 10 edits before being given the permission to move articles (ie I have no arrow on the top of my page yet). So once this happens I will continue. Thanks again for the encouragement. Now I have to stop reading what random people said about the editor who reviewed the editor who commented on my edit. So this is Wikipedia. :-) Theskepticaloptimist (talk) 22:20, 12 November 2010 (UTC)[reply]

Suggested text for the Afatinib article (Feb 2013)

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I just wanted to post here on the Afatinib Talk page as well - I have inserted a suggestion for an update for this article via the WikiProject Pharmacology Talk page, as I would like the community to review. It focuses on balanced, accurate and up-to-date information. You can find it here: http://en.wikipedia.org/wiki/Wikipedia_talk:WikiProject_Pharmacology#Update_to_current_article_on_afatinib Looking forward to feedback! --Sagschneider (talk) 08:49, 15 February 2013 (UTC)[reply]

Don't be too shy, just add your text! Someone (probably me) will fix any formatting issues afterwards. Just remember to keep your text readable for the layman, and avoid too much jargon (especially in the lead section). Cheers, ἀνυπόδητος (talk) 17:16, 18 February 2013 (UTC)[reply]
Now archived to Wikipedia_talk:WikiProject_Pharmacology/Archive 7#Update_to_current_article_on_afatinib - Looks similar to the April 2013 suggestion below - Most/all of it looks good and some still a worthwhile addition to the current article. - Rod57 (talk) 14:10, 27 January 2016 (UTC)[reply]

Update to the current article needed (April 2013)

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Hi Wikiproject Pharmacology community members and other editors,

With the goal of increasing the accuracy and amount of balanced & up-to-date information available online for afatinib, I suggested new text for this article back in January. I had some great feedback from some editors via the community Talk page (http://en.wikipedia.org/wiki/Wikipedia_talk:WikiProject_Pharmacology#Update_to_current_article_on_afatinib) and I tried to update the references and text to my best ability to comply. (See below for exact text suggestion)

At this point in time, I wanted to check back in with everyone and ask someone in the community to review again and make the edits where/when appropriate directly on the main article.I highly appreciate the feedback on this. --Sagschneider (talk) 12:24, 29 April 2013 (UTC)[reply]


Afatinib

Afatinib (trade name under discussion) is a drug currently under investigation by Boehringer Ingelheim for the treatment of various types of cancer that are driven by mutations and overexpression of a family of proteins called ErbB. The cancers include Epidermal growth factor receptor (ErbB1) mutation positive (M+) Non-small-cell lung carcinoma (NSCLC,) HER2 (ErbB2) positive metastatic breast cancer (mBC) and squamous head and neck cancer (HNSCC).

As for clinical trials, the LUX-Lung, LUX-Breast and LUX-Head & Neck clinical trial programmes are investigating afatinib in a number of clinical settings within these disease areas.


Mechanism of action

Afatinib, an irreversible ErbB Family Blocker, inhibits signal transduction of all kinase receptors from the ErbB Family, blocking key pathways involved in cell growth and division.[1] [2] Since ErbB Family signalling can be initiated by a variety of homo- and heterodimers, a combined inhibition of more than one ErbB Family member may provide a more successful blockade of ErbB Family signaling.[3]

The ErbB Family is frequently dysregulated in cancer cells; overexpression of ErbB receptors can lead to the development of a variety of solid tumours[4] and is associated with poor prognosis and advanced-stage cancers.[5] Over-activation of these receptors triggers intracellular signalling cascades that ultimately cause uncontrolled tumour cell proliferation, migration and metastasis, and inhibition of apoptosis.[6] There are a variety of mechanisms leading to constitutive activation of this signal-transduction pathway, including receptor mutation (e.g. EGFR mutation in lung cancer), receptor overexpression (e.g. HER2 overexpression in breast cancer) or ligand overexpression.[7]


Development status

Afatinib is currently being investigated for ErbB-driven malignancies including Non-small-cell lung carcinoma (NSCLC,) metastatic Breast cancer (mBC) and squamous head and neck cancer (HNSCC).

The LUX-Lung clinical trial programme is investigating afatinib in a number of clinical settings with advanced NSCLC. One of the pivotal trials in this programme is LUX-Lung 3, a global, multicentre, randomised, open-label, Phase III trial, studying afatinib in EGFR M+ NSCLC patients who had not received prior therapy (first-line). Positive results from this registration trial were presented at the American Society of Clinical Oncology Annual Meeting 2012 and a further analysis was presented at ESMO 2012 (European Society for Medical Oncology).[8] [9] [10] Data from this trial formed the basis of submission of afatinib for marketing authorisation to the European Medicines Agency (EMA) and a New Drug Application to the US Food and Drug Administration (FDA) for treatment of patients with EGFR M+ NSCLC.[11]

Afatinib has also shown clinical efficacy in EGFR M+ second-line NSCLC (LUX-Lung 2 Phase II trial)[12] and is being investigated in later lines of treatment (LUX-Lung 1 and 5).[13] [14] LUX-Lung 6, the sister trial to LUX-Lung 3, is investigating afatinib as a first-line treatment in EGFR M+ NSCLC patients in Asia (China, Republic of Korea and Thailand).[15]

To further explore the potential of afatinib as an NSCLC treatment, Boehringer Ingelheim has initiated two trials aimed at comparing afatinib head-to-head with targeted treatment agents. LUX-Lung 7 is a Phase IIb trial evaluating afatinib versus gefitinib as a first-line treatment in EGFR M+ NSCLC patients.[16] LUX-Lung 8 is a Phase III trial evaluating afatinib head-to-head versus erlotinib in second-line treatment of squamous cell carcinoma of the lung.[17]

The LUX-Breast clinical trial programme consists of three key clinical trials, investigating the safety and efficacy of afatinib in patients with mBC. In total, an estimated 1020 patients will be enrolled into the LUX-Breast clinical trials in more than 300 locations in more than 30 countries. The LUX-Head & Neck 1 and LUX-Head & Neck 2 Phase III trials, initiated in January 2012 and October 2011 respectively are evaluating afatinib in patients with metastatic and recurrent HNSCC, and in patients with locally advanced disease, respectively.

References:

  1. ^ Solca, F. et al. Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker. J Pharmacol Exp Ther 2012, 343(2)
  2. ^ Ou, S-H L. Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): A better mousetrap? A review of the clinical evidence. Critical Reviews in Oncology / Hematology 2012, 83(3)
  3. ^ Reid, A. et al. 2007. Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu). European Journal of Cancer 2007 43(3)
  4. ^ Hanahan, D. et al. The Hallmarks of Cancer. Cell 2000, 100(1)
  5. ^ Normanno, N. et al. The ErbB receptors and their ligands in cancer: an overview. Current Drug Targets 2005, 6(3)
  6. ^ Hanahan, D. et al. The Hallmarks of Cancer. Cell 2000, 100(1)
  7. ^ Wieduwilt, M.J. et al. The epidermal growth factor receptor family: biology driving targeted therapeutics. Cellular and Molecular Life Sciences 2008, 65
  8. ^ Yang JCH et al. LUX-lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. Oral Presentation at 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2012. Abstract no: LBA7500
  9. ^ Sequist L. V. et al. LUX-Lung 3: Symptom and health-related quality of life results from a randomized phase III study in 1st-line advanced NSCLC patients harbouring EGFR mutations. ESMO 2012 Congress
  10. ^ Dr. Li Reviews Afatinib Data From the LUX-Lung 3 Trial. OncLive 2013
  11. ^ European Medicines Agency, Medicines under evaluation. January 2013
  12. ^ Ou, S-H L. Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): A better mousetrap? A review of the clinical evidence. Critical Reviews in Oncology / Hematology 2012, 83(3)
  13. ^ LUX-Lung 5: Afatinib Plus Weekly Paclitaxel Versus Investigator's Choice of Single Agent Chemotherapy Following Afatinib Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib
  14. ^ BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)
  15. ^ LUX-Lung 6: A Randomized, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation
  16. ^ LUX-Lung 7: A Phase IIb Trial of Afatinib(BIBW2992) Versus Gefitinib for the Treatment of 1st Line EGFR Mutation Positive Adenocarcinoma of the Lung
  17. ^ LUX-Lung 8: A Phase III Trial of Afatinib (BIBW 2992) Versus Erlotinib for the Treatment of Squamous Cell Lung Cancer After at Least One Prior Platinum Based Chemotherapy

Suggested text for the Afatinib article

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I would like to propose some minor updates to the current article for afatinib to reflect the fact that afatinib has now been approved by various regulatory authorities including the European Medicines Agency for the treatment of non-small cell lung cancer. To do this though I would think that there would need to be a consensus in favour, so I would like to propose that someone from this WikiProject Pharmacology group or another interested editor review the suggestions and reply and/or accept and implement, if possible. The suggestion is below for review.Sagschneider (talk) 15:09, 23 October 2013 (UTC)[reply]

Afatinib[1] (INN; trade name Gilotrif GIOTRIF® (Europe, Taiwan, Mexico and Chile), GILOTRIF™ (U.S.), previously Tomtovok and Tovok[2]) is an ErbB Family Blocker angiokinase inhibitor approved to be used as a drug against non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim.[3][4] Afatinib is approved in the U.S., Europe, Taiwan, Mexico and Chile for the first-line treatment of patients with distinct types of metastatic NSCLC. [1] [2] [3]

  1. ^ U.S. GILOTRIF™ Prescribing Information
  2. ^ Taiwanese Food and Drug Administration
  3. ^ European Medicines Agency


Suggested edit to Afatinib Article (2014)

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I would like to propose a further update to the current article for afatinib. Information on recently reported scientific data (e. g. at ASCO Annual Meeting 2014), relevant to the approved indication for afatinib as a treatment for non-small cell lung cancer is missing from the “Medical uses” section of the current article. Below I have drafted some suggested wording about this data for inclusion in the article, for your consideration. I look forward to hearing your thoughts on this suggestion and, as always, am grateful for any feedback and advice.

In addition we propose an update to ongoing clinical research, which investigates afatinib in head and neck squamous carcinoma as well as other ErbB driven tumors.

Suggest wording:

Afatinib was investigated as first-line therapy in two pivotal, Phase III trials, LUX-Lung 3 and 6. Both studies were large, randomized trials comparing afatinib to standard of care chemotherapy, LUX-Lung 3 in a Caucasian and Asian population, LUX-Lung 6 in a solely Asian population. Both trials met their respective primary endpoint, progression-free survival (PFS). Data presented at the recent American Society of Clinical Oncology (ASCO) Annual Meeting 2014 from the LUX-Lung 3 and LUX-Lung 6 trials demonstrated a significant overall survival (secondary endpoint) benefit for NSCLC patients subgroups with the most common type of EGFR mutation, Del19, compared to standard chemotherapy. A combined exploratory analysis of the LUX-Lung 3 and LUX-Lung 6 trials demonstrated a prolongation of overall survival (secondary endpoint) in lung cancer patients whose tumours harbour common EGFR mutations (Del19/L858R), compared with standard chemotherapy..

Sagschneider (talk) 10:07, 8 December 2014 (UTC)[reply]

Looks fine but we need references. - Rod57 (talk) 14:23, 27 January 2016 (UTC)[reply]

LUX-lung 7 study results

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BI's GIOTRIF/GILOTRIF beats AstraZeneca's IRESSA in mid-stage lung cancer study. could mention under clinical trials. - Rod57 (talk) 13:46, 27 January 2016 (UTC)[reply]

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