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At ASCO, Next-Gen EGFR Inhibitors Show Early Promise in Lung Cancer Patients with T790M Mutations

"Next-generation EGFR inhibitors for treating metastatic non-small cell lung cancer patients who have acquired resistance to first-generation drugs in this class accurately hit mutant EGFR tumor cells and caused fewer serious side effects, early data presented at a major cancer conference showed.


"Researchers at the American Society of Clinical Oncology's annual meeting here this week, presented preliminary data from human studies on three next-generation EGFR inhibitors: AstraZeneca's AZD9291, Clovis Oncology's CO-1686, and Hanmi Pharmaceutical's HM61713. All three agents showed promising activity against patients who had EGFR mutations, had received prior treatment with a first-generation tyrosine kinase inhibitor – such as Roche's Tarceva (erlotinib) and AstraZeneca's Iressa (gefinitib) – and had T790M mutations."


Editor's note: For a more reader-friendly explanation of these new drugs, check out the "Drug resistance" section of our Chief Scientist's latest blog post.

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GenomeWeb  |  Jun 4, 2014

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Gefitinib, Erlotinib Increased Risk for Interstitial Lung Disease in Patients with Advanced NSCLC

Gefitinib, Erlotinib Increased Risk for Interstitial Lung Disease in Patients with Advanced NSCLC | Lung Cancer Dispatch | Scoop.it

"Patients treated with advanced non–small cell lung cancer treated with gefitinib and erlotinib demonstrated a significant increased risk for all-grade and fatal interstitial lung disease events, according to results of a systematic review and meta-analysis.


"Erlotinib (Tarceva, Genentech) and gefitinib (Iressa, AstraZeneca), both of which are oral epidermal growth factor receptor tyrosine kinase inhibitors, are commonly used during treatment of advanced NSCLC. However, the overall risk for interstitial lung disease events are not known."

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Healio  |  Feb 5, 2014

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Molecular Marker Predicts Response to Iressa and Tarceva

Molecular Marker Predicts Response to Iressa and Tarceva | Lung Cancer Dispatch | Scoop.it

A molecule named Mig 6 may help predict how much a patient will benefit from EGFR inhibitors like Tarceva (erlotinib) or Iressa (gefitinib). Preliminary results from an ongoing study reveal that cancer cells that are resistant to EGFR inhibitors have high Mig 6 levels. In an animal model of non-small cell lung cancer (NSCLC) without EGFR mutations, higher Mig 6 levels predicted more resistance to EGFR inhibitor treatment. Finally, NSCLC patients with low Mig 6 levels were more likely to survive for over a year after EGFR inhibitor treatments. Mig 6 may help identify patients who would most benefit from EGFR inhibitors.

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Medical Xpress | Sep 5, 2013

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Trial Investigating Iressa After Lung Cancer Surgery Terminated Early

A clinical trial investigating whether the cancer drug gefinitib (Iressa) can improve outcomes after lung cancer surgery has been ended early. The trial followed patients who were given either Iressa or a placebo after receiving surgery to completely remove their non-small cell lung cancer (NSCLC). When two other studies showed no benefit of Iressa in similar disease situations, the trial was terminated. Due to the early termination of the trial, no firm conclusions can be drawn from the results. However, analysis of the already collected data suggests that Iressa likely did not improve survival, or delay cancer recurrence in this patient population, and may have indeed been harmful.

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CancerNetwork | Sep 2, 2013

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Patients with Drug-Resistant Lung Cancer Might Benefit from New Drug CO-1686

Patients with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene often improve significantly when treated with EGFR inhibitors like erlotinib (Tarceva) or gefitinib (Iressa). However, in virtually all cases, patients eventually develop resistance to these drugs. Resistance to EGFR inhibitors is frequently associated with patients developing an additional mutation in the EGFR gene called T790M. Hope for these patients may come from a new EGFR inhibitor designed to target the T790M mutation, called CO-1686. Preliminary results from an ongoing early clinical trial of CO-1686 show that the drug shrank tumors in at least a subset of patients with EGFR-mutant advanced NSCLC who were resistant to EGFR inhibitors and carried the T790M mutation.

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Reuters | June 3, 2013

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Switching from Iressa to Tarceva Halts Drug-Induced Immune Suppression in Lung Cancer Patient

Switching from Iressa to Tarceva Halts Drug-Induced Immune Suppression in Lung Cancer Patient | Lung Cancer Dispatch | Scoop.it

Neutropenia (a reduction in white blood cells) is a rare, but potentially serious side effect of the cancer drug gefitinib (Iressa). Iressa is used to treat non-small cell lung cancer (NSCLC) with mutations in the EGFR gene. A patient with EGFR-mutant advanced adenocarcinoma of the lung (a type of NSCLC) was treated with Iressa. Her tumor shrank, but she experienced severe neutropenia, leaving her at risk of dangerous infections. She was switched to erlotinib (Tarceva), another EGFR inhibitor, after which her neutropenia cleared up. The patient has since continued on Tarceva without neutropenia or cancer progression for over nine months. This case suggests that Iressa-induced neutropenia can be safely treated by switching to Tarceva, although caution should be used in drawing conclusions from a single case study.

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Lung Cancer | Mar 14, 2013

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Mutations in EGFR and KRAS Genes Do Not Predict Lung Cancer Outcome by Themselves

Non-small cell lung cancer (NSCLC) patients with mutations in the EGFR gene are likely to benefit from treatment with tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa), while KRAS mutations predict poor TKI response. A study of patients who were not taking TKIs and had stages I/II/III NSCLC that had been surgically removed found no difference in recurrence or survival between patients with or without EGFR or KRAS mutations. This finding suggests that, while EGFR and KRAS mutations are useful for identifying patients who may benefit from targeted treatments like TKIs, they do not predict overall clinical outcomes by themselves.


Research paper: http://graphics.tx.ovid.com/ovftpdfs/FPDDNCOBHDNMDO00/fs047/ovft/live/gv024/00000421/00000421-900000000-99450.pdf

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American Journal of Clinical Oncology | Jan 24, 2013

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Scientists Discuss EGFR Inhibition and Its Limitations in NSCLC

A review of recent research discusses EGFR inhibition in the treatment of non-small cell lung cancer (NSCLC). Blocking EGFR using drugs called EGFR-tyrosine kinase inhibitors (TKIs) is an effective treatment for advanced NSCLC in patients with mutations in the EGFR gene. However, chemotherapy remains the standard of care for advanced NSCLC without EGFR mutations. Unfortunately, patients commonly develop drug resistance to TKIs like erlotinib (Tarceva) or gefitinib (Iressa). Newer TKIs like afatinib, which target multiple proteins and irreversibly inhibit them, are being explored in clinical trials and may be effective in patients who have become resistant to first-generation TKIs.

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Journal of Thoracic Oncology | Jan 29, 2013

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Various Approaches to EGFR Inhibition Can Be Useful in Lung Cancer

Various Approaches to EGFR Inhibition Can Be Useful in Lung Cancer | Lung Cancer Dispatch | Scoop.it

A review of recent research discusses EGFR inhibition in the treatment of lung cancer. Scientists have now demonstrated that EGFR-tyrosine kinase inhibitors (TKIs), either by themselves or combined with chemotherapy, are effective first-line treatments for advanced non-small cell lung cancer (NSCLC) with EGFR mutations, and as second-line or maintenance treatments for all advanced NSCLC. TKIs like erlotinib (Tarceva) or gefitinib (Iressa), or anti-EGFR antibodies like cetuximab (Erbitux), may also enhance the effectiveness of radiation therapy for locally advanced NSCLC. Other biomarkers, such as KRAS mutations, may also help predict response to EGFR inhibition therapy.

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Biomarker Research | Jan 16, 2013

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Study Suggests Iressa Effective for Elderly Patients with EGFR-Mutant Lung Cancer

A retrospective study in Japan examined 55 patients age 75 years or over with inoperable non-small cell lung cancer (NSCLC) who had a mutation in the EGFR gene and received gefitinib (Iressa) as first-line therapy. The treatment was generally well-tolerated, and patients experienced longer periods without cancer progression (median: 13.8 months) and longer overall survival (median: 29.1 months) than commonly reported for similar patients. While studies using control groups will need to confirm that Iressa is indeed more effective than standard chemotherapy or a placebo, these findings suggest that Iressa may be a preferable first-line treatment in elderly patients with advanced EGFR-mutant NSCLC.

 

Research paper: http://link.springer.com/article/10.1007/s12032-012-0450-2/fulltext.html

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Medical Oncology | Jan 13, 2013

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Gefitinib is Safe and Effective for Elderly Patients with EGFR-mutated NSCLC

Gefitinib is Safe and Effective for Elderly Patients with EGFR-mutated NSCLC | Lung Cancer Dispatch | Scoop.it

A recent study indicates that gefitinib (Iressa™) could be a suitable first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC) patients over age 75 years, marking the first time the drug has been shown to be safe and effective in this population. Gefitinib may be preferable to standard chemotherapy for elderly patients because of its proven antitumor efficacy and mild toxicity.

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Journal of Thoracic Oncology | Sep 2012

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Erlotinib and Gefitinib Offer Similar Benefit in EGFR-Mutated Non–Small Cell Lung Cancer

Erlotinib and Gefitinib Offer Similar Benefit in EGFR-Mutated Non–Small Cell Lung Cancer | Lung Cancer Dispatch | Scoop.it

"A retrospective study has shown that two targeted therapy drugs—erlotinib (Tarceva) and gefitinib (Iressa)—achieved similar outcomes among people with metastatic or recurrent non–small cell lung cancer (NSCLC) harboring an EGFR mutation. These EGFR tyrosine kinase inhibitors have previously been reported to offer benefit over standard chemotherapy as first-line treatment of EGFR-positive advanced NSCLC. The study findings by Lim et al are published in the Journal of Thoracic Oncology.


"Erlotinib is used worldwide, and gefitinib is widely used in Asian countries and recently in Europe (only for patients with tumors harboring EGFR mutations) but not in the United States. Indirect comparisons of the two agents have resulted in inconsistency with regard to progression-free survival, and until now, the agents have not been compared head-to-head in patients with EGFR-positive NSCLC."


Editor's note: Erlotinib and gefitinib are targeted therapies. Learn more.

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The ASCO Post  |  Mar 26, 2014

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Pfizer Cancer Drug Fails in Two Late Stage Studies

In a recent phase III clinical trial, the cancer drug dacomitinib was no more effective than a placebo at prolonging survival for patients with advanced non-small cell lung cancer (NSCLC) for whom standard therapy had failed. Like the targeted drugs erlotinib (Tarceva) and gefitinib (Iressa), dacomitinib blocks the protein EGFR, but it also inhibits a number of similar, related proteins. Another trial compared dacomitinib to Tarceva in NSCLC patients who had previously received at least one EGFR inhibitor. Dacomitinib did not increase time without cancer worsening compared to Tarceva. Results from a third phase III trial, which compares dacomitinib to Iressa in NSCLC patients with EGFR mutations, are expected next year.

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Bloomberg Businessweek  |  Jan 27, 2014

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Cancer Researcher: No Need for Further EGFR Inhibitor Versus Chemotherapy Trials

No more trials comparing EGFR inhibitors to chemotherapy in patients with non-small cell lung cancer (NSCLC) should be conducted, argues an editorial by cancer researcher Corey Langer. Eight separate trials have found that EGFR inhibitors like erlotinib (Tarceva), gefitinib (Iressa), and afatinib (Gilotrif) produce better results than chemotherapy in NSCLC patients who have mutations in the EGFR gene. No further confirmation is needed, Langer contends. Instead, research should focus on ways to overcome the drug resistance that many patients eventually develop to EGFR inhibitors, meaningfully extending overall survival in NSCLC, and directly comparing the relative effectiveness and safety of Tarceva, Iressa, and Gilotrif.

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Medscape | Sep 3, 2013

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Funding Strategy Needed to Support EGFR Mutation Testing in Canada

Funding Strategy Needed to Support EGFR Mutation Testing in Canada | Lung Cancer Dispatch | Scoop.it

Funding represents a decisive barrier to the nationwide implementation of genetic testing for a key lung cancer mutation in Canada, a recent study finds. Patients with non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene frequently benefit from treatment with EGFR inhibitors. AstraZeneca, makers of the EGFR inhibitor gefinitinb (Iressa), reimbursed Canadian laboratories for offering EGFR mutation testing to patients with advanced non-squamous NSCLC for 12 months. EGFR mutation testing was rapidly adopted into routine clinical practice in Canada. However, testing rates dropped sharply once the reimbursement program ended. Researchers conclude that a national strategy is needed to provide resources for continued EGFR testing.

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Medical Xpress | Jul 25, 2013

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Testing for EGFR and ALK Mutations Recommended for All Lung Adenocarcinoma Patients

Testing for EGFR and ALK Mutations Recommended for All Lung Adenocarcinoma Patients | Lung Cancer Dispatch | Scoop.it

All patients with advanced adenocarcinoma of the lung, a type of non-small cell lung cancer (NSCLC), should be tested for mutations in the EGFR and ALK genes, according to guidelines developed by three prominent professional medical societies. Mutations in these genes predict a much higher likelihood of benefitting from treatment with EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa), or ALK inhibitors like crizotinib (Xalkori), respectively. The tests should be performed for all adenocarcinoma patients as soon as advanced disease is detected, regardless of sex, race, smoking history, or other clinical risk factors.

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MedPage Today | Apr 5, 2013

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Zolinza May Circumvent TKI Resistance in Some Lung Cancer Patients

Tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva) and gefitinib (Iressa) are effective treatments for many patients with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene. However, patients who also have a certain version of the BIM gene are resistant to TKIs. Vorinostat (Zolinza), a member of a family of drugs called histone deacetylase (HDAC) inhibitors, restored the antitumor activity of Iressa in EGFR-mutant NSCLC cells and in animal models of EGFR-mutant NSCLC that carried the resistant BIM version. Combining Zolinza with TKIs may therefore help circumvent TKI resistance in patients who have the resistant form of BIM.

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Cancer Research | Feb 4, 2013

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TKIs Are Effective First-Line Treatment in EGFR-Mutant Advanced Non-Small Cell Lung Cancer

TKIs Are Effective First-Line Treatment in EGFR-Mutant Advanced Non-Small Cell Lung Cancer | Lung Cancer Dispatch | Scoop.it

Four phase III studies compared the tyrosine kinase inhibitors (TKIs) erlotinib (Tarceva) or gefitinib (Iressa) to standard chemotherapy as first-line treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). TKI treatment increased progression-free survival (ie, the length of time without the cancer worsening), but did not improve overall survival compared to chemotherapy. In one study, TKI-treated patients maintained a higher quality of life for longer than chemotherapy-treated patients. The findings suggest that TKI treatment should become the standard first-line treatment in advanced NSCLC with mutations in the EGFR gene.


Research paper: http://link.springer.com/article/10.1007/s11523-013-0258-9/fulltext.html

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Targeted Oncology | Jan 30, 2013

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Inhibition of MET May Help Overcome TKI Drug Resistance in Lung Cancer

Inhibition of MET May Help Overcome TKI Drug Resistance in Lung Cancer | Lung Cancer Dispatch | Scoop.it

Tyrosine kinase inhibitors (TKIs) that block EGFR are effective treatments for many cases of advanced non-small cell lung cancer (NSCLC), but are limited by the fact that patients will eventually develop resistance against them. Overexpression of the MET gene may contribute to EGFR-TKI resistance, suggesting that combined inhibition of both EGFR and MET may prevent or overcome this drug resistance. Several MET inhibitors have been developed, including cabozantinib (Cometriq), tivantinib, onartuzumab, and ficlatuzumab, and ongoing trials are investigating the safety and effectiveness of combining them with an EGFR-TKI like erlotinib (Tarceva) or gefitinib (Iressa).


Research paper: http://theoncologist.alphamedpress.org/content/early/2013/01/25/theoncologist.2012-0262.full.pdf

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The Oncologist | Jan 28, 2013

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Novel Drugs Show Promise in Non-Small Cell Lung Cancer

Novel Drugs Show Promise in Non-Small Cell Lung Cancer | Lung Cancer Dispatch | Scoop.it

Medical experts at the 2012 Chemotherapy Foundation Symposium presented data on the growing number of targeted treatments for non-small cell lung cancer (NSCLC) with so-called driver mutations—specific genetic mutations that drive tumor growth. Among the drugs showing promise in adenocarcinoma are ridaforolimus for KRAS-mutant tumors, ganetespib for ALK- or KRAS-mutant tumors, and afatinib for EGFR-mutant tumors. For squamous cell carcinoma (SCC), new potential treatments include AZD4547 and BGJ398 (FGFR1-mutant), dasatinib and nilotinib (DDR2 mutant), Tarceva and Iressa (EGFRvIII-mutant), and Yervoy and Cadi-05 (all SCC), while anti–PD-1 antibodies such as BMS-936558 may be effective for both adenocarcinoma and SCC.

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OncLive | Jan 14, 2013

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Postoperative TKI Treatment Benefits Patients with EGFR Mutations

New research suggests that erlotinib (Tarceva®) and gefitinib (Iressa™) can reduce the risk of recurrence after removal of EGFR-mutant lung cancer tumors. The study followed patients with stage I-III lung cancer who underwent tumor removal. Patients with EGFR-mutant tumors who were treated with either of the two TKI drugs after resection had a lower risk of recurrence or death than patients who did not receive the adjuvant therapy.

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Journal of Thoracic Oncology | Dec 2012

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