Final analysis of the observational GioTag study: Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small cell lung cancer

Ridgefield, Conn., September 2, 2020 – Boehringer Ingelheim today announced the final analysis from GioTag, a real-world retrospective, observational study. The study assessed the impact of first-line treatment with Gilotrif® (afatinib) followed by osimertinib in Del19/L858R epidermal growth factor receptor mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) patients with acquired T790M mutations, the most common mechanism of resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Results showed that across the 203 patients included in the analysis, sequential treatment of afatinib followed by osimertinib provided a median overall survival (OS) of 37.6 months (90% confidence interval (CI): 35.5–41.3) and median time to treatment failure (TTF) of 27.7 months (90% CI: 26.7–29.9).

Dr. Maximilian J. Hochmair, Medical Oncologist, Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute and coordinating investigator of the GioTag study said, “The real-world data reported here represent the most mature analysis of OS with sequential afatinib and osimertinib to date. The final GioTag results support the results of our previous analyses, that sequential afatinib and osimertinib treatment could be a feasible and effective therapeutic strategy in a broad, real-world population of patients with EGFR M+ NSCLC who acquire T790M.”

Results showed that Asian and Del19-positive patients saw a median OS of 44.8 months (90% CI: 37.0–57.8) and 41.6 months (90% CI: 36.9–45.0) respectively. Median TTF was 37.1 months (90% CI: 28.1–40.3) and 30.0 months (90% CI: 27.6–31.9) for these groups, respectively. In the 31 Asian patients with Del19-positive disease, median OS was 45.7 months (90% CI: 38.2–57.8) and TTF was 40.0 months (90% CI: 36.4–45.0).  

Clinical effectiveness was also consistent across patient subgroups which are sometimes unexamined in prospective randomized clinical trials due to poor prognosis characteristics. For these subgroups, median OS was 31 months (90% CI: 19.5–45.0) in patients with stable brain metastases, 36.9 months (90% CI: 33.0–44.8) in patients aged ≥65 years, and 32 months (90% CI: 24.5–34.5) in those with ECOG PS ≥2. TTF for these groups was 22.2 months (90% CI: 16.8–29.9), 27.3 months (90% CI: 20.4-31.3) and 22.2 months (90% CI: 16.0–26.5), respectively.

Bjoern Rueter, M.D., Therapeutic Area Head Oncology, USA, at Boehringer Ingelheim, said, “Resistance to first-line EGFR TKI therapy is an inevitability, making subsequent treatment options following disease progression a key consideration. While no prospective overall survival data are currently available to compare different sequential regimens of EGFR TKIs, the final GioTag study data provide important insight into the use of afatinib followed by osimertinib. The GioTag data suggest a potential for prolonged periods of time on non-chemotherapy treatment in patients with EGFR Del19 who develop T790M mutation-positive tumors.”

About GioTag
GioTag was a real-world retrospective, observational study which assessed the impact of first-line treatment with afatinib followed by osimertinib in Del19/L858R EGFR M+ non-small cell lung cancer patients with acquired T790M mutations, the most common mechanism of resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). The study was conducted across ten countries: Austria, Canada, Israel, Italy, Japan, Singapore, Slovenia, Spain, Taiwan and USA; NCT03370770. Data were collected between December 2017 and December 2019. Inclusion was restricted to patients who initiated osimertinib treatment ≥10 months prior to enrolment to avoid early censoring and ensure mature data. A maximum of 15 patients were enrolled per site. Data were sourced either from sites directly approached by Boehringer Ingelheim (n = 77; 38%) or from electronic health records (n = 126; 62%) supplied by Cardinal Health (OH, USA). For quality assurance of the documented patient observations, source data verification was performed on approximately 30% of included patients. Main limitations of this study were its retrospective nature and potential for selection bias. The other main limitation of the study was a lack of a comparator arm, which limits interpretation of the results.

What Is Gilotrif?

Gilotrif is a prescription medicine that is used to treat people with non-small cell lung cancer (NSCLC) that:

• has certain (non-resistant) abnormal epidermal growth factor receptor (EGFR) gene(s). Your healthcare provider will perform a test to make sure that Gilotrif is right for you.
• has spread to other parts of the body (metastatic), and
• has not been previously treated for metastatic lung cancer.

It is not known if Gilotrif is safe and effective in treating people with lung cancer that has resistant abnormal EGFR genes.

or

is used to treat people with squamous cell lung cancer that:

• has spread to other parts of the body, and
• has been previously treated with chemotherapy that contains platinum.

It is not known if Gilotrif is safe and effective in children.

Important Safety Information for Gilotrif® (afatinib) Tablets

Before you take Gilotrif, tell your doctor if you:

• have kidney or liver problems
• have lung or breathing problems other than lung cancer
• have a history of an ulcer, a tear (perforation) in your stomach or intestine, or diverticular disease (inflammation) in parts of your large intestine
• have a history of severe dry eye or any other eye problems. Tell your doctor if you wear contact lenses.
• have heart problems
• have any other medical conditions
• are pregnant or plan to become pregnant. Gilotrif can harm your unborn baby.
  • Females who are able to become pregnant should use effective birth control during treatment with Gilotrif and for at least 2 weeks after your last dose of GILOTRIF. Talk to your doctor about birth control methods that may be right for you.
  • Tell your doctor right away if you become pregnant or think you are pregnant during treatment with Gilotrif.
• are breastfeeding or plan to breastfeed. It is not known if Gilotrif passes into your breast milk. Do not breastfeed while taking Gilotrif and for 2 weeks after your last dose of Gilotrif. Talk to your doctor about the best way to feed your baby if you take Gilotrif.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Gilotrif may affect the way other medicines work, and other medicines may affect the way Gilotrif works. Taking certain medicines with Gilotrif may increase your risk of developing a tear (perforation) in your stomach or intestine.

What to avoid while taking Gilotrif
Limit your time in the sun. Gilotrif can make your skin sensitive to sunlight. You could get or have worsening rash or acne. You could get a severe sunburn. Use sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight during treatment with Gilotrif.

Gilotrif may cause serious side effects, including:

• Diarrhea. Diarrhea is common with Gilotrif and may sometimes be severe. Severe diarrhea can cause loss of body fluid (dehydration) and kidney problems that can sometimes lead to death. During your treatment with Gilotrif, your doctor should prescribe medicines to treat diarrhea. Take this medicine exactly as your doctor tells you to. Tell your doctor if you have diarrhea. Get medical attention right away if your diarrhea does not go away or becomes severe.
• Skin reactions. Gilotrif can cause redness, rash, and acne. It is important to get treatment for skin reactions as soon as you notice them. Take medicines to help skin reactions exactly as your doctor tells you to. Get medical attention right away if you develop severe skin reactions such as peeling or blistering of the skin, or blisters in your mouth.
• Lung or breathing problems. Gilotrif may cause inflammation of the lung that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your doctor right away if you have any new or worsening lung problems, or any combination of the following symptoms: trouble breathing or shortness of breath, cough, or fever.
• Liver problems. Gilotrif can cause liver problems that can sometimes lead to death. Tell your doctor right away if you have any symptoms of a liver problem which may include:
  • yellowing of your skin or the white part of your eyes (jaundice)
  • dark or brown (tea-colored) urine
  • pain on the upper right side of your stomach area (abdomen)
  • bleeding or bruising more easily than normal
  • feeling very tired

Your doctor will do blood tests to check your liver function during your treatment with Gilotrif.

• Tear (perforation) in your stomach or intestine. Tears in your stomach or intestine can happen with Gilotrif and can sometimes lead to death. Your risk of developing a tear in your stomach or intestine may be increased if you:
  • take certain medicines with Gilotrif including: corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDS), and certain other medicines.
  • have a history of stomach or intestinal ulcers, or if you have had diverticular disease (inflammation in parts of the large intestine)

Get medical help right away if you develop severe stomach-area (abdomen) pain during treatment with Gilotrif.

• Eye problems. Tell your doctor right away if you have symptoms of eye problems. Symptoms may include:
  • eye pain, swelling, redness, or tearing
  • blurred vision
  • sensitivity to light
  • other changes in your vision
• Heart problems. Tell your doctor right away if you have any symptoms of a heart problem which may include:
  • new or worsening shortness of breath while at rest or with activity
  • cough
  • tiredness
  • swelling of your ankles, feet, or legs
  • feeling that your heart is pounding or racing (palpitations)
  • sudden weight gain

Your doctor may change your dose, temporarily stop or permanently stop treatment with Gilotrif if you have certain side effects.

The most common side effects of Gilotrif include diarrhea, rash, acne, mouth sores, nail inflammation, dry skin, decreased appetite, nausea, vomiting, and itching.

Gilotrif may cause decreased fertility in females and males. This may affect your ability to have a child. Talk to your doctor if this is a concern for you.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of Gilotrif. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see Prescribing Information and Patient Information.

About Boehringer Ingelheim in Oncology
Cancer takes. Takes away time. Takes away loved ones. At Boehringer Ingelheim Oncology, we are giving patients new hope by taking cancer on. We are dedicated to collaborating with the oncology community on a shared journey to deliver leading science. Our primary focus is in lung and gastrointestinal cancers, with the goal of delivering breakthrough, first-in-class treatments that can help win the fight against cancer. Our commitment to innovation has resulted in pioneering treatments for lung cancer and we are advancing a unique pipeline of cancer cell directed agents, immune oncology therapies and intelligent combination approaches to help combat many cancers.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Making new and better medicines for humans and animals is at the heart of what we do. Our mission is to create breakthrough therapies that change lives. Since its founding in 1885, Boehringer Ingelheim is independent and family-owned. We have the freedom to pursue our long-term vision, looking ahead to identify the health challenges of the future and targeting those areas of need where we can do the most good.

As a world-leading, research-driven pharmaceutical company, more than 51,000 employees create value through innovation daily for our three business areas: Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. In 2019, Boehringer Ingelheim achieved net sales of around $21.3 billion (19 billion euros). Our significant investment of over $3.9 billion (3.5 billion euros) in R&D drives innovation, enabling the next generation of medicines that save lives and improve quality of life.In 2018, Boehringer Ingelheim achieved net sales of around $20.7 billion (17.5 billion euros). R&D expenditure of almost $3.7 billion (3.2 billion euros) corresponded to 18.1 per cent of net sales.

We realize more scientific opportunities by embracing the power of partnership and diversity of experts across the life-science community. By working together, we accelerate the delivery of the next medical breakthrough that will transform the lives of patients now, and in generations to come.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation and is part of the Boehringer Ingelheim group of companies. In addition, there are Boehringer Ingelheim Animal Health in Duluth, GA and Boehringer Ingelheim Fremont, Inc. in Fremont, CA.

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