Overall survival data from LUX-Lung 7 head-to-head trial of Gilotrif^®(afatinib) versus Iressa^® (gefitinib) presented at ESMO

Ridgefield, Conn., October 9, 2016 – Boehringer Ingelheim today announced results from the LUX-Lung 7 trial that directly compared the efficacy and safety of second-generation EGFR-directed therapy Gilotrif^® (afatinib) and first-generation Iressa^® (gefitinib), in the first-line treatment of patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). The trial investigated overall survival (OS) as a primary endpoint and a reduction in the risk of death (14%) was observed for patients treated with afatinib versus gefitinib. The median survival of patients treated with afatinib was 27.9 months compared to 24.5 months for those receiving gefitinib, without reaching significance. The OS outcomes observed with afatinib were consistent across common EGFR mutation types.

Details of the analysis will be presented today at the European Society of Medical Oncology (ESMO) 2016 Congress in Copenhagen, Denmark, October 7 – 11 (abstract #LBA43 - Oral presentation, NSCLC, metastatic 1, Sunday, October 9, 11:45 - 12:00 CEST (5:45 – 6:00 ET)).

“The LUX-Lung 7 trial provides new insight into first-line treatment options for EGFR mutation-positive NSCLC patients and is the first global head-to-head trial directly comparing two EGFR-directed therapies,” commented Shirish Gadgeel, M.D., leader of the Thoracic Oncology Multidisciplinary, Karmanos Cancer Center, Detroit. “These study findings may help inform treatment decisions for patients whose tumors have EGFR mutations.”

Updated results also confirmed the primary analysis that showed the global Phase IIb LUX-Lung 7 trial met two of its three co-primary endpoints of progression-free survival (PFS) by independent review and time to treatment failure (a measure of time between start and discontinuation of treatment for any reason). Results from the primary analysis, presented in 2015, showed that afatinib significantly reduced the risk of lung cancer progression and the risk of treatment failure, both by 27% versus gefitinib. The improvement in PFS became more pronounced over time. After two years of treatment, more than twice as many patients on afatinib were alive and progression-free than those on gefitinib (after 18 months; 27% vs 15% and after 24 months; 18% vs 8%). Additionally, significantly more patients experienced an objective response (ORR; a clinically meaningful decrease in tumor size) with afatinib when compared to gefitinib.

Both afatinib and gefitinib demonstrated similar improvements in patient-reported outcome measures in the LUX-Lung 7 trial with no significant differences in health-related quality of life with afatinib compared to gefitinib treatment. Treatment with both afatinib and gefitinib were generally tolerable, leading to an equal rate of treatment-related discontinuation in both arms (6%). Adverse events (AEs) observed in the trial were consistent with the known safety profiles of both treatments. The overall frequency of serious AEs was 44.4% for afatinib and 37.1% for gefitinib. The most common grade ≥3 related AEs with afatinib were: diarrhea (13%) and rash/acne (9%), and with gefitinib: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) increase (9%) and rash/acne (3%). Drug-related interstitial lung disease was reported for four patients on gefitinib and no patients on afatinib. Dose modification of afatinib was available in patients who met a set criteria in order to better manage AEs. As gefitinib is only available in one dose formulation, no dose reduction was administered.

“We believe that the latest results of the LUX-Lung 7 trial data adds to the growing body of evidence that reinforces the treatment benefits of afatanib in patients with these types of tumors,” said Martina Flammer, M.D., Vice President, Clinical Development & Medical Affairs Specialty Care, Boehringer Ingelheim.

Afatinib is approved in over 70 countries for the first-line treatment of EGFR mutation-positive NSCLC. Approval of afatinib in this indication was based on the primary endpoint of PFS from the LUX-Lung 3 clinical trial where afatinib significantly delayed tumor growth when compared to standard chemotherapy. In addition, afatinib is the first treatment to have shown an OS benefit for patients with specific types of EGFR mutation-positive NSCLC compared to chemotherapy. A significant OS benefit was demonstrated independently in the LUX-Lung 3 and 6 trials for patients with the most common EGFR mutation (del19) compared to chemotherapy. Afatinib is also approved in the U.S., EU and other markets for the treatment of patients with advanced squamous cell carcinoma (SqCC) of the lung whose disease has progressed on or after treatment with platinum-based chemotherapy. Approval of afatinib in this indication is based on results of the LUX-Lung 8 study, which showed a significantly improved overall survival and progression-free survival compared to Tarceva^® (erlotinib) in patients with SqCC of the lung.

About the LUX-Lung 7 trial
LUX-Lung 7 is the first global, head-to-head trial comparing second- and first-generation EGFR-directed therapies (afatinib and gefitinib respectively) for patients with EGFR mutation-positive NSCLC who received no prior treatment. The Phase IIb trial included 319 patients with advanced stage NSCLC harboring common EGFR mutations (del19 or L858R). The trial’s co-primary endpoints were PFS by independent review, time to treatment failure and OS; and the secondary endpoints included ORR, disease control rate, tumor shrinkage, patient-reported outcomes and safety.

Results from the primary analysis: compared to gefitinib, afatinib significantly improved:

• PFS (HR=0.73; 95% CI, 0.57‒0.95; p=0.017; median: 11.0 months [afatinib] versus 10.9 months [gefitinib]). The improvement in PFS with afatinib was consistent across pre-defined clinical subgroups, including gender, age, race and EGFR mutation type
• Time to treatment failure (HR=0.73; 95% CI, 0.58‒0.92; p=0.0073; median: 13.7 months [afatinib] versus 11.5 months [gefitinib])
• ORR (70% vs 56%, p=0.0083)

Data from the trial showed a reduction in the risk of death for patients treated with afatinib compared to gefitinib, without reaching significance (HR=0.86; 95% CI, 0.66‒1.12; p=0.2580; median: 27.9 months [afatinib] versus 24.5 months [gefitinib]). These OS data have a maturity of 71%, with further analysis to follow once full maturity has been reached.

What is GILOTRIF?

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

• that has certain types of abnormal epidermal growth factor receptor (EGFR) genes. Your doctor will perform a test to check for certain types of abnormal EGFR genes, and make sure that GILOTRIF is right for you. GILOTRIF may be used when you have not had previous treatment for cancer that has spread to other parts of the body. It is not known if GILOTRIF is safe and effective in treating lung cancer with other abnormal EGFR genes.

or

• that is squamous type and has spread to other parts of the body after you have tried chemotherapy that contains platinum.

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

IMPORTANT SAFETY INFORMATION ABOUT GILOTRIF

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 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. You should not become pregnant while taking GILOTRIF.
  • Women 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 while taking 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.

What to avoid while taking GILOTRIF

Limit your time in the sun. GILOTRIF can make your skin sensitive to the sun. 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 while you are taking GILOTRIF if you have to be in sunlight.

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.

• 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

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

GILOTRIF may cause decreased fertility in females and males. Talk to your doctor if you have concerns about your fertility.

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 the full Prescribing Information, including Patient Information.

GF CONS ISI APRIL 2016

About Boehringer Ingelheim in Oncology
Boehringer Ingelheim’s oncology research is driven by a passion to advance clinical practice and a determination to improve the lives of patients who are battling cancer. Through our own scientific innovation and partnerships, we are focused on discovering and providing novel best-in-class, breakthrough cancer medications that fit the needs of patients, caregivers and healthcare professionals. We have a clear strategy to become a leader in the field of lung cancer. Boehringer Ingelheim has successfully launched two products globally for NSCLC that have been widely adopted and established as valuable additions to current clinical practice. Continuous insights and learnings from research and development are key parts of innovation and our way forward to advance clinical practice in lung cancer and other cancer types.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation.

Boehringer Ingelheim is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with 145 affiliates and more than 47,000 employees. Since its founding in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel treatments for human and veterinary medicine.

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