Afatinib Improves Progression-Free Survival vs Erlotinib in Second-Line Treatment of Advanced Squamous Cell Carcinoma of the Lung

“In the phase III LUX-Lung 8 trial reported in The Lancet Oncology, Soria et al found that the irreversible ErbB-family inhibitor afatinib (Gilotrif) significantly improved progression-free and overall survival vs the EGFR tyrosine kinase inhibitor erlotinib as second-line treatment in patients with stage IIIB or IV squamous cell carcinoma of the lung who had disease progression after four or more cycles of platinum-based chemotherapy.

“In this open-label trial, 795 patients from 23 countries were randomly assigned between March 2012 and January 2014 to receive afatinib at 40 mg/d (n =398) or erlotinib at 150 mg/d (n = 397). The primary endpoint was progression-free survival on independent central review in the intent-to-treat population…

“The investigators concluded: ‘The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung.’ “


Boehringer's Giotrif Beats Roche's Tarceva on Lung Cancer Survival

“Boehringer Ingelheim’s Giotrif has shown a greater survival benefit than Roche’s Tarceva in previously-treated patients with advanced squamous cell carcinoma of the lung.

“According to data from the LUX-Lung 8 trial, published in The Lancet Oncology, Giotrif (afatinib) extended overall survival to a median of 7.9 months compared to 6.8 months on Tarceva (erlotinib), reducing the risk of death by 19%.

“The study also met its primary endpoint showing a significant improvement in progression-free survival over Tarceva, which is an approved and recommended treatment option for advanced SCC of the lung following treatment with first-line platinum-based chemotherapy.”


Exelixis Announces Positive Results from Phase 2 Trial of Cabozantinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer

“Exelixis, Inc. EXEL, +9.21% today announced positive results from a phase 2 clinical study evaluating cabozantinib as a treatment for EGFR wild-type non-small cell lung cancer (NSCLC). The trial, Study E1512, is a randomized phase 2 trial by the ECOG-ACRIN Cancer Research Group of cabozantinib and erlotinib, alone or in combination, as second- or third-line therapy in patients with metastatic EGFR wild-type NSCLC. Exelixis previously announced positive top-line results from this trial in November 2014. Data from the trial will be presented today during an oral presentation (Abstract #8003) at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO), which is being held this week in Chicago, Illinois. Study chair Joel Neal, M.D., Ph.D., of ECOG-ACRIN’s Thoracic Cancer Committee and an Assistant Professor of Medicine (Oncology) at Stanford University/Stanford Cancer Institute will present the results.

“Study E1512 met its primary endpoint, demonstrating significant increases in progression-free survival (PFS) for cabozantinib and the combination of cabozantinib plus erlotinib when individually compared to the erlotinib arm. The median PFS for the combination of cabozantinib and erlotinib was 4.7 months versus 1.9 months for erlotinib alone, a more than two-fold increase that corresponds to a 65% reduction in the risk of disease worsening (hazard ratio [HR]=0.35, 80% CI 0.23-0.52, p=0.0005). The median PFS for cabozantinib monotherapy was 4.2 months versus 1.9 months for erlotinib alone, a more than doubling that corresponds to a 62% reduction in the risk of disease worsening (HR=0.38, 80% CI 0.27-0.55, p=0.0004).”


Erlotinib Trial Indicates That It Could Be Used Before Surgery in Stage III Lung Cancer

“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.”


Blood Samples as Surrogates for Tumor Biopsies in Patients with Lung Cancer

“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.”


New Drugs Aim to Defeat Tumor Resistance to EGFR Inhibitors


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…


Stereotactic Body Radiation Therapy plus Chemotherapy Improves Survival among Stage 4 Lung Cancer Patients

“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.’ “


Stage IV NSCLC That Worsens during Chemo Could Be Treated with Erlotinib and SBRT

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).”


Results of New Drug, ASP8273, Show Response in Patients with Treatment-Resistant NSCLC

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 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.”