“Erlotinib showed promise as neoadjuvant therapy in patients with epidermal growth factor receptor (EGFR) mutant stage IIIA-N2 non-small-cell lung cancer (NSCLC) who demonstrated good disease control with tolerable toxicity following treatment.
“Dr Baohui Han, Pulmonary Department, Shanghai Chest Hospital, Shanghai, China presented findings from a single arm, phase II clinical trial during the New Treatment Avenues Proffered Papers session at the European Lung Cancer Conference, 15 to 18 April 2015 in Geneva, Switzerland. The trial aimed to evaluate efficacy and safety of erlotinib as neoadjuvant treatment in patients with stage IIIA-N2 NSCLC and activating EGFR mutation.
“The trial’s primary endpoint was radical resection rate. Secondary endpoints included pathological complete response rate (pCR), objective response rate (ORR), disease free survival (DFS), overall survival (OS), safety profile, and explorative biomarkers.
“This study screened 155 patients and subsequently enrolled 44 patients with stage IIIA N2 NSCLC and 25 patients with IIIA N2 NSCLC plus activating EGFR (exon 19 or 21) mutations. All patients had ECOG performance status 1 and had been previously untreated for stage IIIA-N2 NSCLC, that was confirmed by endobronchial ultrasound.”
“A study examined the feasibility of using circulating free DNA (cfDNA) from blood samples of patients with advanced non-small-cell lung cancer as a surrogate for tumor biopsies to determine tumor-causing epidermal growth factor receptor (EGFR) mutations and then correlate that with expected patient outcomes, according to a study published online by JAMA Oncology.
“The analysis was a secondary objective of the EURTAC trial, which demonstrated the efficacy of erlotinib compared with standard chemotherapy for the first-line treatment of European patients with advanced non-small-cell lung cancer (NSCLC) with oncogenic EGFR mutations (exon 19 deletion or L858R mutations in exon 21) in tumor tissue.
“Rafael Rosell, M.D., of the Hospital Germans Trias I Pujol, Badalona, Spain, and coauthors examined EGFR mutations in cfDNA isolated from 97 baseline blood samples.
“Results show that in 76 samples from 97 (78 percent) patients, EGFR mutations in cfDNA were detected. Median overall survival was shorter in patients with the L858R mutation in cfDNA than in those with the exon 19 deletion (13.7 vs. 30 months). For patients with the L858R mutation in tissue, median overall survival was 13.7 months for patients with the L858R mutation in cfDNA and 27.7 months for those in whom the mutation was not detected in cfDNA. For the 76 patients with EGFR mutations in cfDNA, only erlotinib treatment was an independent predictor of longer disease progression-free survival.”
In recent years, many people with non-small cell lung cancer (NSCLC) have been successfully treated with drugs called EGFR inhibitors. But over time, most patients develop resistance, and the drugs stop working. Researchers are hard at work developing new drugs to help patients who can no longer be treated with EGFR inhibitors.
EGFR inhibitors get their name from a gene called EGFR. Many lung cancer tumors have mutations in this gene. These mutations convert EGFR from a normal gene into a cancer gene that initiates and promotes cancer growth. Approximately 10% to 15% of white and 30% to 35% of Asian patients with NSCLC have EGFR mutations. Continue reading…
“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.’ “
The gist: Stage IV non-small cell lung cancer (NSCLC) patients whose cancer worsened during platinum-based chemotherapy might benefit from treatment with the drug erlotinib and stereotactic body radiation (SBRT) therapy.
“Treatment with stereotactic body radiation therapy and erlotinib appeared highly effective in patients with metastatic stage IV non–small cell lung cancer who progressed on prior platinum-based chemotherapy, according to results of a single-arm phase 2 study.
“Patients with stage IV NSCLC who progress on first-line chemotherapy historically demonstrate poor survival outcomes, and they typically fail in original sites of gross disease, according to background information provided by researchers.
“Puneeth Iyengar, MD, PhD, assistant professor of radiation oncology at UT Southwestern Medical Center, and colleagues hypothesized that stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse.
“Iyengar and colleagues evaluated PFS, OS and other outcomes among 24 patients (median age, 67 years) who underwent second- or later-line treatment with SBRT plus erlotinib (Tarceva; Genentech, Astellas).”
The gist: People with non-small cell lung cancer (NSCLC) that has both the EGFR and T790M mutations might benefit from a new drug. The drug is called ASP8273. A clinical trial tested ASP8273 in volunteer patients in Japan. In the trial, it shrank people’s tumors. More research is needed, but it is hoped that the drug might be a good alternative for people whose tumors are resistant to drugs like erlotinib, gefitinib and afatinib.
“In a second presentation looking at new ways of treating non-small cell lung cancer (NSCLC) that has both the EGFR and T790M mutations, researchers will tell the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, that an oral drug called ASP8273 has caused tumour shrinkage in patients in a phase I clinical trial in Japan.
“Mutations of the epidermal growth factor (EGFR) occur in about 30-35% of Asian patients with NSCLC (and in 10-15% of Caucasian patients). EGFR inhibitors called tyrosine kinase inhibitors (TKI), such as erlotinib, gefitinib and afatinib, can be used to treat EGFR-mutated NSCLC. However, these patients will eventually develop resistance to EGFR TKI therapy, rendering their disease resistant to current treatments. A further mutation called T790M accounts for 60% of this acquired resistance.
“ASP8273 is a new drug that inhibits the EGFR mutation and the T790M resistance mutation. Earlier research in mice had shown that it caused NSCLC to disappear completely, and so a phase I clinical trial was started in January 2014 to assess the drug’s safety and efficacy in humans.
“Twenty-four Japanese patients have enrolled so far to receive one of six levels of doses (25, 50, 100, 200, 400 and 600mg) once a day. A further seven patients have been enrolled into a second group to evaluate doses of 100mg, 200mg and 400mg a day (a dose escalation study), and the researchers are planning to enrol a total of 124 patients. Cancer had progressed in all the patients after prior treatment with EGFR TKI therapy, and most of them had the T790M mutation.”
The gist: Scientists recently tested whether the drug dacomitinib is better than erlotinib for treating people with advanced non-small cell lung cancer (NSCLC) who had already received a previous treatment. In terms of the amount of time that passed without a patient’s disease worsening, the scientists found that dacomitinib was no better than erlotinib. They also found that dacomitinib was no better than erlotinib for people with advanced NSCLC whose tumors did not have mutations in the KRAS gene (as detected by molecular testing). These findings came from a clinical trial in which the treatments were tested in volunteer patients.
“In a phase III ARCHER 1009 trial reported in The Lancet Oncology, Ramalingam et al found no progression-free survival benefit of the irreversible pan-HER tyrosine kinase inhibitor dacomitinib vs erlotinib among all patients with pretreated non–small cell lung cancer (NSCLC) or among those with KRAS wild-type tumors…
“In this double-blind trial, 878 patients from 134 centers in 23 countries with locally advanced or metastatic NSCLC and progression after one or two previous chemotherapy regimens were randomly assigned between June 2011 and March 2013 to receive oral dacomitinib at 45 mg/d (n = 439 [256 of which were KRAS wild-type tumors]) or erlotinib at 150 mg/d (n = 439 [263 of which were KRAS wild-type tumors]). Randomization was stratified by histology, ethnicity, Eastern Cooperative Oncology Group performance status, and smoking status. The coprimary endpoints were progression-free survival on independent review for all patients and for the subgroup with KRAS wild-type tumors.
“The dacomitinib and erlotinib groups were generally balanced for age (median, 64 and 62 years, 48% and 39% ≥ 65 years), sex (66% and 63% male), ethnicity (76% and 75% white, 21% and 20% Asian), histology (adenocarcinoma in 69% and 68%), disease stage (IV in 91% and 92%), never-smoker status (18% and 19%), KRAS status (wild-type in 58% and 60%, mutant in 16% and 15%, unknown in 26% and 25%), EGFR status (wild-type in 74% and 76%, mutant in 11% and 10%, unknown in 15% and 14%), and number of previous systemic therapies (1 in 58% and 64%, 2 in 40% and 33%)…
“The investigators concluded: ‘Irreversible EGFR inhibition with dacomitinib was not superior to erlotinib in an unselected patient population with advanced non-small-cell lung cancer or in patients with KRAS wild-type tumours. Further study of irreversible EGFR inhibitors should be restricted to patients with activating EGFR mutations.’ ”
Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to compare two different treatment approaches for non-squamous non-small cell lung cancer (NSCLC) with mutations in the EGFR gene. One treatment combined the drugs erlotinib and bevacizumab, and the other treatment was simply erlotinib alone. Based on the results, the researchers say that erlotinib plus bevacizumab could be a new standard treatment for people with NSCLC with EGFR mutations.
“The authors aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non–squamous NSCLC with activating EGFR mutation–positive disease. Erlotinib plus bevacizumab combination could be a new first–line regimen in EGFR mutation–positive NSCLC. Further investigation of the regimen is warranted.”
A series of three new clinical trials (research studies with volunteer patients) is big news for some people affected by early-stage lung cancer. The trials focus on two drugs typically used to treat late-stage adenocarcinoma. These two drugs, Tarceva and Xalkori, may also help stage I, II, and IIIA patients prevent relapse (return of cancer) after their tumors have been surgically removed. The new clinical trials will put the treatments to the test. Continue reading…