Showing posts sorted by relevance for query Erlotinib. Sort by date Show all posts
Showing posts sorted by relevance for query Erlotinib. Sort by date Show all posts

Saturday, September 12, 2020

Combined drug treatment for lung cancer and secondary tumors



In continuation of my update on alectiniberlotinib and  osimertinib

Alectinib structure.svg 
                                                                   alectinib

                                                   Erlotinib Structural Formulae.png 
                                                                     erlotinib
                                                  Osimertinib.svg
                                                                             Osimertinib


Researchers at Kanazawa University report in the Journal of Thoracic Oncology a promising novel approach for a combined treatment of the most common type of lung cancer and associated secondary cancers in the central nervous system. The approach lies in combining two cancer drugs, with one compensating for a resistance side effect of the other.

In 20 to 40% of patients with cancer, metastasis (the development of secondary tumors) in the central nervous system (CNS) occurs. CNS metastasis impacts negatively on a patient's quality of life, and is associated with a poor health prognosis. In a form of cancer known as ALK-rearranged non-small-cell lung cancer (NSCLC), CNS metastasis is known to persist when drugs targeting primary tumors are used. Now, Seiji Yano from Kanazawa University and colleagues have investigated the origins for the resistence to such drugs, and tested a new therapeutic strategy on a mouse model.

The researchers looked at the drug alectinib. Although used in standard treatments for advanced ALK-rearranged NSCLC, approximately 20 to 30% of patients treated with alectinib develop CNS metastasis, which is attributed to acquired resistance to the drug.
By treating mice first injected with tumor cells with alectinib daily for 16 weeks, the scientists obtained a mouse model displaying alectinib resistance. By biochemical analyses of the mouse brains, Yano and colleagues were able to link the resistance to the activation of a protein known as epidermal growth factor receptor (EGFR). This activation is, in turn, a result of an increase in production of amphiregulin (AREG), a protein that binds to EGFR and in doing so 'activates' it.
Based on this insight, the researchers tested the effect of administering drugs used for inhibiting the action of EGFR in combination with alectinib treatment. The experiments showed that a combination treatment of alctinib with either erlotinib or osimertinib—two existing EGFR-inibiting drugs—prevented the progression of CNS metastasis, controlling the condition for over 30 days.
The scientists conclude that the combined use of alectinib and EGFR-inhibitors could overcome alectinib resistance in the mouse model of leptomeningeal carcinomatosis (LMC), a particular type of CNS metastasis. Quoting Yano and colleagues: "Our findings may provide rationale for clinical trials to investigate the effects of novel therapies dual-targeting ALK and EGFR in ALK-rearranged NSCLC with alectinib-resistant LMC."
Non-small-cell lung cancer
Non-small-cell lung carcinoma (NSCLC) and small-cell lung carcinoma (SCLC) are the two types of lung cancer. 85% of all lung cancers are of the NSCLC type. NSCLCs are less sensitive to chemotherapy than SCLCs, making drug treatment of the highest importance.
Alectinib is a drug used for treating NSCLC, with good efficiency. However, 20-30% of patients taking the  develop secondary cancer in the central nervous system (CNS), which is associated with an acquired resistance to alectinib. Seiji Yano from Kanazawa University and colleagues have now made progress towards a novel therapy against this resistance: a combination of alectinib with other drugs.
Epidermal growth factor receptor inhibitors
The drugs that Yano and colleagues tested in combination with alectinib on a mouse model were of a type known as epidermal growth factor receptor (EGFR) inhibitors, including osimertinib and erlotinib. Both are being used as medication for treating NSCLC. The former was approved in 2017 as cancer treatment by the U.S. Food and Drug Administration and the European Commission. Yano and colleagues obtained results showing that EGFR inhibitors counteract resistance to alectinib and have therefore potential in novel therapies for NSCLC and secondary cancers in the CNS.
https://medicalxpress.com/news/2017-11-osimertinib-progression-free-survival-asian-egfr-mutated.html

Saturday, October 1, 2016

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study

In continuation of my updates on Erlotinibgemcitabine and capecitabine
Additional treatments for locally advanced pancreatic cancer don't appear to boost survival, a new French study reports.
Researchers looked at the effects of adding a second drug -- erlotinib (Tarceva) -- to the initial round of chemotherapy. They also tested whether adding radiation to a second round of chemotherapy (chemoradiotherapy) would offer any survival benefit.
Erlotinib Structural Formulae.png erlotinib (Tarceva)
Unfortunately, the addition of the second drug didn't help people live longer, and those on chemoradiotherapy didn't fare any better.
"Chemoradiotherapy was not superior to chemotherapy," said the study's senior author, Dr. Pascal Hammel. Hammel is from the department of gastroenterology-pancreatology at Beaujon Hospital, in Clichy, France.
The study was funded by the pharmaceutical company Roche, the maker of Tarceva, and the French National Institute of Cancer.
More than 53,000 Americans are diagnosed with pancreatic cancer annually, the U.S. National Cancer Institute (NCI) says. About 42,000 Americans die each year from the disease, the NCI reports.
The new study focused on 449 people with pancreatic cancer. Their average age was just over 63.
All received standard four-month chemotherapy with the drug gemcitabine (Gemzar). Gemzar is currently used to treat a range of cancers, including pancreatic, ovarian, breast, and non-small cell lung cancers, the drug's labeling information says. For the study, about half the patients (219) also took Tarceva along with Gemzar.
Gemcitabine.svg gemcitabine (Gemzar).
After completing initial treatment, imaging tests revealed that 269 patients appeared to have tumors that were under control. That meant their cancer was stable and didn't appear to have spread, or metastasized.
But the tumors couldn't be surgically removed because they had developed around the arteries surrounding the pancreas, study authors said.
About half this group of stable patients (136) received two additional months of the same chemotherapy regimen. The other half (133) was treated with a combination of radiation and the chemotherapy drug capecitabine (Xeloda).
 capecitabine (Xeloda)
After three years of follow-up, the researchers found that patients given Gemzar chemotherapy alone survived an average of 13.6 months. Those given the combination of Gemzar and Tarceva had an average survival of 11.9 months, the study found.
Patients treated with chemoradiotherapy lived an average of 15.2 months. Those who got chemotherapy alone lived an average of 16.5 months, the study found.
Hammel said there's still work to be done to improve the results of both chemotherapy and radiotherapy treatments.
But for now, Dr. Deborah Schrag agreed that "the French trial demonstrates that routine addition of chemo-radiation following initial chemotherapy for patients with locally advanced pancreatic cancer does not improve survival compared to continued chemotherapy." Schrag, chief of the Division of Population Sciences, Medical Oncology, at the Dana-Farber Cancer Institute in Boston, wrote an accompanying editorial in the same issue of the journal.
"[And] given the burdens of daily radiation therapy, there is no routine role for the application of this treatment strategy," added Schrag.
Schrag said it's possible there might be a certain group of pancreatic cancer patients who could get some measurable benefit from radiation. "Further evaluation of the tumor samples from the study participants might help to more precisely determine who might benefit from radiation, and such data are eagerly awaited," she said.

Tuesday, December 10, 2013

Toxicity limits benefits of bevacizumab–erlotinib NSCLC maintenance therapy

In continuation of my update on bevacizumab and erlotinib 



Two targeted anticancer drugs used together after first-line chemotherapy for advanced stage non-small-cell lung cancer (NSCLC) improve progression-free survival (PFS), the results of a large, prospective study show.

Median PFS was 4.8 months for patients treated with bevacizumab plus erlotinib versus 3.7 months for those treated with bevacizumab plus placebo (hazard ratio [HR] = 0.71). There was no overall survival (OS) advantage, however, and the two-drug combination was associated with more adverse events than bevacizumab alone, say the study investigators.

Sunday, June 24, 2012

New combination of two previously approved FDA drugs treat lung cancer

In continuation of my update on Erlotinib..

Dr. Narla's laboratory focuses on the identification and characterization of the genes and pathways involved in cancer metastasis. By studying the functional role of the KLF6 tumor suppressor gene, Dr. Narla and his team have identified new signaling pathways regulated by this gene family thus providing new insight into cancer diagnosis and treatment. The team's research found that KLF6 and FOXO1, both tumor suppressor genes, are turned off as cancer spreads through the body. By using a combination of two existing FDA drugs -Erlotinib (left structure), a targeted cancer drug, and Trifluoperazine (below right structure), a medication used to treat schizophrenia, the team developed an understanding of the properties that turn these critical genes back on, initiating tumor cells to die.
Since first discovering the KLF6 gene 13 years ago as a medical student at the Mount Sinai School of Medicine in the laboratory of Dr. Scott Friedman, Dr. Narla has been involved in the identification and characterization of the KLF6 gene and its role in cancer development and the progression of cancer.
Read details at JCI.....

Wednesday, March 18, 2015

New treatment approach may improve survival rates for certain patients with stage 4 lung cancer

A clinical trial that combined stereotactic body radiation therapy with a specific chemotherapy regimen more than doubled survival rates for certain stage 4 lung cancer patients, UT Southwestern Medical Center cancer researchers report.

The combination of the chemotherapy regimen, erlotinib, with stereotactic body radiation therapy, known as SBRT, improved overall survival time to 20 months compared to historic 6- to 9- month survival times among erlotinib-only treated patients. The combination improved progression free survival - the time without the reappearance of cancer − from the historical two to four months to 14.7 months for similarly selected lung cancer patients.

"Our approach dramatically changed the pattern of relapse. We saw a shift in failure from existing, local sites to new, distant sites," said senior author Dr. Robert Timmerman, Director of the Annette Simmons Stereotactic Treatment Center, and Vice Chairman of Radiation Oncology at UT Southwestern. "This shift resulted in a surprisingly long remission from the reappearance of cancer in treated patients."

Tuesday, November 29, 2016

FDA Approves Gilotrif (afatinib) for Patients with Squamous Cell Carcinoma of the Lung

I continuation of my update on Afitinib

Boehringer Ingelheim  announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for Gilotrif® (afatinib) tablets for the treatment of patients with advanced squamous cell carcinoma of the lung whose disease has progressed after treatment with platinum-based chemotherapy. The U.S. approval follows the recent marketing authorization of Gilotrif in this patient population by the European Commission. Gilotrif, an oral, once-daily EGFR-directed therapy, is currently approved in the U.S. for the first-line treatment of specific types of EGFR mutation-positive NSCLC.
Afatinib2DACS.svg afatinib
“We are pleased to bring a proven therapy to patients suffering from advanced squamous cell carcinoma of the lung who have progressed despite chemotherapy,” said Sabine Luik, MD, senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “This approval is further evidence of Boehringer Ingelheim’s strong commitment to bringing new treatment options to the lung cancer community.”
Squamous cell carcinoma (SqCC) of the lung is associated with a poor prognosis, limited survival and symptoms like cough and dyspnea. The median overall survival (OS) after diagnosis of advanced SqCC is around one year.
LUX-Lung 8 clinical trial investigator Shirish Gadgeel, MD, leader of the Thoracic Oncology Multidisciplinary Team at the Karmanos Cancer Center, Detroit, commented: “The overall survival data and significant delay in lung cancer progression seen in the global head-to-head Phase III trial demonstrated that Gilotrif is an effective new treatment option in this patient population.”
The sNDA was based on results of the head-to-head LUX-Lung 8 trial in patients with SqCC of the lung whose tumors progressed after first-line chemotherapy. Gilotrif, compared to erlotinib, demonstrated:
  • Significant delay in progression of lung cancer (PFS, progression-free survival, primary endpoint), reducing the risk of cancer progression by 18%
  • Significant improvement in overall survival (OS, key secondary endpoint), reducing the risk of death by 19%
  • Significantly improved disease control rate (51% vs 40%; P=0.002)
The most common adverse reactions observed with Gilotrif (reported in at least 20% of study patients) were diarrhea (75%), rash or acne (70%), stomatitis (mouth sores) (30%), decreased appetite (25%), and nausea (21%).
LUX-Lung 8 (NCT01523587) is part of the Gilotrif LUX-Lung program – the largest collection of clinical trials of any EGFR tyrosine kinase inhibitor (TKI), with over 3,760 patients across eight studies conducted around the world. The comprehensive LUX-Lung program includes two pivotal studies in the first-line setting for EGFR mutation-positive patients, LUX-Lung 3 and LUX-Lung 6, which compared Gilotrif to chemotherapy regimens. In addition, the program included two head-to-head studies (LUX-Lung 7 and LUX-Lung 8) of Gilotrif versus first-generation EGFR TKIs gefitinib and erlotinib, respectively. The LUX-Lung program has involved over 680 sites in 40 countries, reflecting the strong partnership between Boehringer Ingelheim and the lung cancer specialist community.

Thursday, February 5, 2015

First-line dacomitinib may improve advanced NSCLC survival



Dacomitinib.svg 




Preliminary research suggests that the second-generation tyrosine kinase inhibitor (TKI) dacomitinib (see right structure)may improve progression-free survival (PFS) in patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.

Noting that the majority of patients develop resistance to the first-generation TKIs, such as gefitinib and erlotinib (below structures from left and right side respectively), Pasi Jänne (Dana Farber Cancer Institute, Boston, Massachusetts, USA) and co-workers explain that alternative agents are needed to improve patient outcomes.

Gefitinib structure.svg Erlotinib Structural Formulae.png

The open-label, phase II trial included 89 treatment-naïve patients with stage IIIB or IV NSCLC who were selected for dacomitinib once-daily treatment on the basis of clinical markers (never or former light smokers) or molecular markers (absence of KRASmutation in non-Asian patients or EGFR mutation).

First-line dacomitinib may improve advanced NSCLC survival

Thursday, December 10, 2015

Early trial results in lung cancer



Erlotinib Structural Formulae.png


Results from early phase trials investigating different therapeutic agents in lung cancer patients were presented during the third Presidential Session at the European Cancer Congress in Vienna, Austria. Here we summarise two studies reported at the session.

Erlotinib (structure) plus bevacizumab promising in EGFR T790M-positive advanced NSCLC patients. 

Rolf Stahel, from University Hospital Zurich in Switzerland, presented the findings of the BELIEF trial [1] on behalf of his fellow investigators from the Spanish Lung Cancer Group and the European Thoracic Oncology Platform. The phase II trial enrolled 109 patients with metastatic or locally advanced non-squamous non-small-cell lung cancer (NSCLC) harbouring activating epidermal growth factor receptor (EGFR) mutations (either the exon 19 deletion or the exon 21 L858R point mutation).

Of these, 37 (33.9%) patients also carried the EGFR T790M mutation at baseline, while the remaining 72 participants were negative for T790M.

Patients were treated with a combination of everolimus and bevacizumab on the basis of previous preclinical results suggesting that inhibiting both the EGFR and vascular EGFR pathways could be beneficial in the presence of the T790M mutation, explained Stahel.

After a median follow-up of 17.5 months, progression-free survival (PFS) was a median of 13.8 months in the overall cohort, with times of 16.0 and 10.5 months for the T790M-positive and -negative groups, respectively. The corresponding 1-year PFS rates were 56.7%, 72.4% and 49.4%.

Complete responses were achieved by 6.4% of all study participants, 8.1% of those positive for T790M and 5.6% of T790M-negative patients, while partial responses were achieved by 69.7%, 62.2% and 73.6% of patients, respectively.

Thursday, January 18, 2018

Trial shows apple allergen as effective treatment option for birch pollen-related apple allergy

In continuation of my update on Osimertinib

Osimertinib.svg
Osimertinib improves progression-free survival compared to standard first line therapy in Asian patients with EGFR-mutated non-small-cell lung cancer (NSCLC), according to the Asian subset analysis of the FLAURA trial presented at the ESMO Asia 2017 Congress, sumultaneously published in The New England Journal of Medicine.
EGFR mutations occur in 30-40% of NSCLC in Asian populations compared to 10-15% in Western populations. The phase III FLAURA trial compared osimertinib, a third generation EGFR-tyrosine kinase inhibitor (TKI), to standard of care EGFR-TKIs (erlotinib or gefitinib) as first line therapy in NSCLC patients with EGFR mutations. A total of 556 patients from Asia, Europe, and North America were randomized 1:1 to treatment with osimertinib or standard of care. Osimertinib improved progression-free survival by 54%.
This subset analysis included the 322 Asian patients in the FLAURA trial, of whom 46 were Chinese, 120 were Japanese, and 156 were from other parts of Asia.
The median progression-free survival was 16.5 months with osimertinib compared to 11.0 months for the standard therapy, with a hazard ratio of 0.54 (95% confidence interval, 0.41-0.72; p<0.0001).
The median duration of response was two-fold higher for patients treated with osimertinib (17.6 months) compared to standard of care (8.7 months). The overall response rate was 80% with osimertinib compared to 75% with standard of care treatment. Median overall survival was not reached. The incidence of grade 3 or higher toxicities was lower for osimertinib (40%) than the standard treatment (48%).
Lead author Professor Byoung Chul Cho, Yonsei Cancer Center, Seoul, Korea, said: "As in the overall trial population, osimertinib provided a significant progression-free survival benefit in Asian patients with EGFR-mutated NSCLC. Asian patients had similar toxicities with osimertinib as the overall FLAURA population. Osimertinib should be the preferred first line treatment for EGFR-mutant NSCLC in Asia."
Commenting on the findings Professor James CH Yang, Chairman, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei City, Taiwan, said: "The results of this subset analysis are quite compatible with the findings in the overall population presented at the ESMO 2017 Congress in Madrid. We can therefore conclude that osimertinib can be considered as the standard of care for the first line treatment of Asian advanced NSCLC patients with EGFR mutations."
"The proportion of patients having adverse events that caused them to stop taking osimertinib was similar in the overall (13%) and Asian (15%) populations," added Yang. "We tend to think osimertinib is a well tolerated drug so these discontinuation rates were surprisingly high and need further investigation."
Yang continued: "Although there was no statistical difference between the hazard ratios for progression-free survival, it was numerically lower in non-Asians (0.34) compared to Asians (0.54). There is an ongoing debate as to whether Asian and non-Asian patients with EGFR mutations have distinct responses to EGFR-TKIs. This might be due to variations in clinical practice rather than biology. A meta-analysis of all relevant studies could shed light on this issue."
"It will also be important to know whether Asian and non-Asian patients in the FLAURA trial with brain metastases had similar outcomes," said Yang.

Wednesday, August 7, 2013

FDA Approves Gilotrif for Late Stage Non-Small Cell Lung Cancer

We know that, Afatinib, trade name Gilotrif, previously Tomtovok and Tovok is an approved drug against non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim. As of  2012, it is undergoing Phase III clinical trials for this indication and breast cancer, as well as Phase II trials for prostate and head and neck cancer, and a Phase I glioma trial. Afatinib is a first-line treatment.


Now FDA has approved...

“Today’s approvals further illustrate how a greater understanding of the underlying molecular pathways of a disease can lead to the development of targeted treatments,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Gilotrif is the second drug approved this year for patients with untreated metastatic NSCLC whose tumors have the EGFR exon 19 deletions or exon 21 L858R substitution mutations.”
In May, the FDA approved Tarceva (erlotinib) for first-line treatment of patients with NSCLC. Tarceva’s new indication was approved concurrently with the cobas EGFR Mutation Test, a companion diagnostic to identify patients with tumors having the EGFR gene mutations.
“The approval of companion diagnostic tests and drugs are important developments in oncology, as they help us bring safe and effective treatments to patients who need them,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health...
More ....





Thursday, August 8, 2013

Phase III trial shows afatinib offers clinical benefit to patients with EGFR mutation positive NSCLC

We know that, Afatinib (INN; trade name Gilotrif, previously Tomtovok and Tovok) is an approved drug against non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim As of July 2012, it is undergoing Phase III clinical trials for this indication and breast cancer, as well asPhase II trials for prostate and head and neck cancer, and a Phase I glioma trial. Afatinib is a first-line treatment
.
In October 2010 a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug. Fall 2010 interim results suggested the drug extendedprogression-free survival threefold compared to placebo, but did not extend overall survival. In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion.

Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive breast cancer) were described as promising by the authors, with 19 of 41 patients achieving benefit from afatinib. Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug.

Mechanism of action :: Like lapatinib and neratinib, afatinib is a next generation tyrosine kinase inhibitor (TKI) that irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases. Afatinib is not only active against EGFR mutations targeted by first generation TKIs like erlotinib or gefitinib, but also against those not sensitive to these standard therapies. Because of its additional activity against Her2, it is investigated for breast cancer as well as other EGFR and Her2 driven cancers.


Sunday, November 20, 2011

Thursday, December 24, 2009

Pyramidine core- a new drug for drug resistant non small cell lung cancers

Dana-Farber investigators hypothesized current agents lose their potency because they don't bind as tightly or fully to the EGFR T790M protein as they ideally should. To improve the fit, researchers led by chemical biologist Nathanael Gray, PhD, prepared a group of inhibitors with a different structural scaffold, known as a pyrimidine core, which, it was thought, would mesh more thoroughly. They lab-tested the agents in NSCLC cells with EGFR T90M and found several that were up to 100 times more potent than quinazolines [erlotinib (Tarceva), gefitinib (Iressa), and cetuximab (Erbitux)] in restricting cell growth. As an unexpected bonus, these compounds were nearly 100 times less powerful at slowing the growth of cells with normal EGFR, suggesting they would be less likely to produce side effects than current drugs. The agent which performed the best is the pyrimidine WZ4002. Those interested, can watch the video description (Pasi Jänne).

http://www.dana-farber.org/abo/news/press/2009/research-yields-new-agent-for-some-drug-resistant-non-small-cell-lung-cancers.html

Thursday, May 10, 2018

FDA Approves Tagrisso (osimertinib) as First-Line Treatment for EGFR-Mutated Non-Small Cell Lung Cancer

Osimertinib.svg

In continuation of my update on OsimertinibAstraZeneca,announced that the US Food and Drug Administration (FDA) has approved Tagrisso (osimertinib) for the 1st-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or exon 21 L858R mutations), as detected by an FDA-approved test. The approval is based on results from the Phase III FLAURA trial, which were presented at the European Society of Medical Oncology 2017 Congress and published in the New England Journal of Medicine.

Dave Fredrickson, Executive Vice President, Head of the Oncology Business Unit at AstraZeneca, said: “Today’s FDA approval of Tagrisso in the 1st-line setting is an exciting milestone for patients and our company. Tagrisso delivered unprecedented median progression-free survival data across all pre-specified patient subgroups, including patients with or without CNS metastases, and could prolong the lives of more patients without their tumors growing or spreading.”
Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA trial, from Winship Cancer Institute of Emory University, Atlanta, said: “The approval of osimertinib (Tagrisso) in the 1st-line setting represents a major advance in the treatment of patients with EGFR mutations and a significant change in the treatment paradigm. Osimertinib (Tagrisso) provides robust improvements in progression-free survival with no unexpected safety signals compared to the previous generation of EGFR inhibitors.”
The FLAURA trial compared Tagrisso to current 1st-line EGFR tyrosine kinase inhibitors (TKIs), erlotinib or gefitinib, in previously untreated patients with locally advanced or metastatic EGFR-mutated (EGFRm) NSCLC. Tagrisso met the primary endpoint of progression-free survival (PFS) (see table below). PFS results with Tagrisso were consistent across all pre-specified patient subgroups, including in patients with or without central nervous system (CNS) metastases. Overall survival data were not mature at the time of the final PFS analysis.
*Confirmed responses
Safety data for Tagrisso in the FLAURA trial were in line with those observed in prior clinical trials. Tagrisso was generally well tolerated, with Grade 3 or higher adverse events (AEs) occurring in 34% of patients taking Tagrisso and 45% in the comparator arm. The most common adverse reactions (≥20%) in patients treated with Tagrisso were diarrhea (58%), rash (58%), dry skin (36%), nail toxicity (35%), stomatitis (29%), fatigue (21%) and decreased appetite (20%).
In the US, Tagrisso is already approved for the 2nd-line treatment of patients with metastatic EGFRm NSCLC, whose disease has progressed on or after a 1st-line EGFR-TKI therapy and who have developed the secondary T790M mutation, as detected by an FDA-approved test. In 2017, Tagrisso was granted Breakthrough Therapy and Priority Review designations by the US FDA in the 1st-line treatment setting. Tagrisso is under regulatory review in the European Union and Japan for use in the 1st-line treatment setting with regulatory decisions anticipated in the second half of 2018.
Tagrisso received its first approval for 1st-line use based on the FLAURA data in Brazil in patients with metastatic EGFRm NSCLC on April 16, 2018.