“While targeting HER2 mutations is mainly associated with breast cancer, there could be therapeutic potential with anti-HER2 agents in non-small cell lung cancer (NSCLC). At this year’s International Lung Cancer Congress, Corey Langer, MD, discussed the potential for afatinib and neratinib—dual inhibitors of EGFR and HER2—in NSCLC, as well as the need for additional research, in order to truly comprehend HER2 targeted therapy in this particular setting.
“HER2 mutations occur in about 2% to 4% of patients with NSCLC, and for the most part, they are mutually exclusive with other molecular drivers (eg, EGFR, KRAS), according to Langer, director of Thoracic Oncology at the Abramson Cancer Center of the University of Pennsylvania. “Similar to EGFR and ALK, the HER2 mutations are more common in women, never-smokers, and adenocarcinoma histology,” Langer added.
“Regarding use of afatinib in these patients, Langer said, ‘There are limited but encouraging data in patients with HER2-mutant NSCLC treated with either afatinib or afatinib plus paclitaxel.’ “
“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.’ “
The gist: Certain Asian patients with non-small cell lung cancer (NSCLC) have better survival results when treated with the drug afatinib (Gilotrif) than with standard chemotherapy. In a clinical trial, these results were true for patients whose tumors had a particular mutation called del19 EGFR. But patients with the Leu858Arg EGFR mutation did just as well on Gilotrif as on standard chemotherapy.
“In an analysis of overall survival in the phase III LUX-Lung 3 and LUX-Lung 6 trials reported in The Lancet Oncology, Yang et al found no significant difference between afatinib (Gilotrif) vs pemetrexed (Alimta)-cisplatin (LUX-Lung 3) or vs gemcitabine-cisplatin (LUX-Lung 6) in previously untreated, predominantly Asian patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma. A significant difference favoring afatinib was found among patients with exon 19 deletion (del19) in both trials, with no difference observed among patients with the Leu858Arg mutation…
“The investigators concluded: ‘Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials.’ ”
The gist: Afatinib (Gilotrif) works better than chemotherapy for people with non-small cell lung cancer (NSCLC) whose tumors have a specific mutation in the EGFR gene. This mutation is known as exon 19 deletion. In a recent clinical trial, some patients with exon 19 deletion were treated with Gilotrif and some with chemotherapy. The patients who received Gilotrif lived significantly longer than the patients who received chemotherapy. All patients had stage IIIB or IV lung adenocarcinoma.
“Patients with lung adenocarcinoma who harbored exon 19 deletion EGFR mutations experienced significantly longer OS when treated with first-line afatinib instead of chemotherapy, according to analyses of results from two phase 3 trials.
“However, researchers did not observe the survival benefit among patients with other types of EGFR mutations.
“ ‘These data provide important evidence about the use of afatinib in patients whose tumors have the del19 mutation and tell us that the standard treatments and approaches should no longer be assumed equivalent for every EGFR mutation,’ Lecia V. Sequist, MD, MPH, medical oncologist at Massachusetts General Hospital Cancer Center and associate professor of medicine at Harvard Medical School, said in a press release.”
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: Asian people with non-small cell lung cancer (NSCLC) whose tumors have a common mutation in the EGFR gene called del19 might have better survival when treated with the drug afatinib instead of chemotherapy. That was the conclusion of a recent clinical trial that tested afatinib in volunteer patients.
“Boehringer Ingelheim has reported positive data from a pre-specified subgroup-analysis of the pivotal Phase III LUX-Lung 3 trial of afatinib in Asian non-small cell lung cancer (NSCLC) patients.
“The trial showed that these patients with the most common type of EGFR mutation, (exon 19 deletion; del19), lived significantly longer after receiving first-line treatment with afatinib compared to chemotherapy.
“The company noted that overall survival results from this pre-specified Asian subgroup-analysis are consistent with the overall del19 population in LUX-Lung , and with the previously reported Asian Phase III LUX-Lung 6 trial, in which patients with the del19 mutation lived a median of more than one year longer if they started treatment with afatinib rather than standard chemotherapy…
“Guangdong Academy of Medical Sciences and Guangdong General Hospital vice-president and principal investigator of the LUX-Lung 6 trial Yi-Long Wu said: ‘Afatinib is the first treatment to demonstrate a significant overall survival benefit for NSCLC patients with the del19 mutation, the most common EGFR mutation.
” ‘More than half of the world’s lung cancer cases occur in Asia. Therefore, EGFR testing for NSCLC patients is important in order to identify the patients eligible for targeted therapy.’ “
Every year, thousands of people gather in Chicago, Illinois, for the American Society of Clinical Oncology (ASCO) Annual Meeting. The largest meeting of its kind, ASCO brings together doctors, researchers, nurses, patient advocates, pharmaceutical company representatives, and more to discuss the latest in cancer research. Here are some of the most exciting new developments in lung cancer research presented last week at ASCO 2014: Continue reading…
“Boehringer Ingelheim today announced results of the pre-specified individual, as well as the exploratory combined, analyses of two Phase III trials (LUX-Lung 3 and LUX-Lung 6). These data, to be presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), demonstrated for the first time that patients with NSCLC with the most common epidermal growth factor receptor (EGFR) mutation (exon 19 deletions; del19) lived more than one year longer if treated with first-line afatinib compared to chemotherapy.”
Editor’s note: This article discusses the results of a clinical trial that tested a targeted drug called afatinib (aka Giotrif, or Gilotrif) on volunteer patients with non-small cell lung cancer (NSCLC). The trial found that patients whose tumors had a particular mutation called del19 in the EGFR gene lived more than one year longer if treated with afatinib than if treated with chemotherapy. EGFR mutations and other mutations are detected via molecular testing, and can be used by oncologists to help develop personalized lung cancer treatment plans.
If you’ve read up on lung cancer research in the last few years, you probably know that large strides have been made in targeted therapies for non-small cell lung cancer (NSCLC). Targeted therapies are drugs that identify and attack specific mutated proteins that are detected in tumors. Because noncancerous cells do not have these specific mutations, targeted therapies can make a beeline for cancer, while leaving healthy tissue unharmed. Continue reading…