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.”


Alternative Sunitinib Treatment Schedules for mRCC May be Worth the Switch

“Some patients with metastatic renal cell carcinoma (mRCC) who are switched from a traditional sunitinib treatment schedule to an alternative schedule fare better on survival measures and suffer fewer adverse events, a Japanese study has found.

“The switch from traditional to alternative schedules was recently found to be effective. But, ‘Japanese patients with mRCC experience substantially different [adverse events] than do patients in many other nations, presumably because of underlying genetic differences’, the authors write.

“They retrospectively reviewed the medical records of 54 patients with mRCC who received sunitinib treatment as first-line therapy between May 2006 and June 2012.”


Newest Drug for ALK-Positive NSCLC Approved in Japan

“The newest drug to target specifically non-small-cell lung cancer (NSCLC) that has tested positive for anaplastic lymphoma kinase (ALK) fusion gene has been granted its first approval worldwide in Japan.

“The drug is alectinib, and will be marketed in Japan by Chugai, a part of the Roche group. It will be available later this year, the company said.

“The Japan Ministry of Health, Labour and Welfare based the approval on a phase 1/2 clinical study (AF-001JP) conducted in Japan for which the primary end point was response rate (and was shown to be >90%).”

Editor’s note: Alectinib is a targeted therapy drug that is specifically meant to treat people with non-small cell lung cancer (NSCLC) whose tumors have mutations in the ALK gene (as detected by molecular testing). Japan has approved the drug for prescription to patients in the country.


Japan Approves World's First PD-1 Drug, Nivolumab

“Ono Pharmaceutical Co has become the first company in the world to get an approval for a PD-1 checkpoint inhibitor, as regulators in Japan gave the green light to nivolumab, developed with Bristol-Myers Squibb, as a treatment for melanoma.

“The drug will be marketed as Opdivo for unresectable melanoma although Ono noted that because of the very limited number of patients treated with nivolumab in Japanese clinical trials, the firm is required to perform a ‘post-marketing use-results survey covering all cases until data on a certain minimum number of patients have been accumulated’.”

Editor’s note: The drug nivolumab is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. Nivolumab is a specific kind of immunotherapy drug known as a “PD-1 checkpoint inhibitor,” since it works by releasing a protein “brake” on the immune system called PD-1. Researchers testing the drug in volunteer patients have found promising results, and Japan has now given the world’s first approval to nivolumab, permitting doctors across the country to prescribe it to people with unresectable melanoma.


No Progression-Free or Overall Survival Benefit With Second- or Third-Line Erlotinib vs Docetaxel in EGFR-Unselected Japanese NSCLC Patients

“In a Japanese phase III trial (DELTA) reported in the Journal of Clinical Oncology, Kawaguchi et al found that erlotinib (Tarceva) was associated with no progression-free survival or overall survival advantage as second- or third-line therapy in EGFR-unselected patients with non–small cell lung cancer.

“In this open-label trial, 301 patients with stage IIIB or IV NSCLC, previous treatment with one or two chemotherapy regimens, evaluable or measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 were randomly assigned between August 2009 and July 2012 to erlotinib at 150 mg daily (n = 150) or docetaxel at 60 mg/m2every 3 weeks (n = 151). The primary endpoint was progression-free survival. In total, 109 patients (73%) in the erlotinib group and 90 (60%) in the docetaxel group had EGFR wild-type disease. Study treatment was third line in 19% and 14%, respectively.”

Editor’s note: This clinical trial tested a drug called erlotinib (brand name Tarceva), which is already known to be an effective treatment for lung cancer patients whose tumors have mutations in the EGFR gene. However, in this trial, the scientists were interested in whether erlotinib might help all patients, regardless of whether EGFR is mutated. The results show that erlotinib is no more effective than chemo for patients without EGFR mutations. But we recently posted another story about a protein test that may predict whether a patient without EGFR mutations might benefit from erlotinib treatment.


Amrubicin and Cisplatin Inferior to Irinotecan Regimen for Small-Cell Lung Cancer

“A combination of amrubicin and cisplatin was inferior to irinotecan and cisplatin in chemotherapy-naïve patients with extensive disease small-cell lung cancer (SCLC) in a phase III trial conducted in Japan. The irinotecan regimen remains the standard treatment for these patients in that country.

“SCLC accounts for 13% of all new cases of lung cancer, and more than half of those patients present with extensive disease. Though SCLC can be very sensitive to chemotherapy, authors of the new study wrote that “rapid emergence of clinical drug resistance has resulted in poor prognosis, with almost all such patients dead with 2 years of initial diagnosis.” Investigators led by Miyako Satouchi, MD, PhD, of the Hyogo Cancer Center in Akashi, Japan, tested the amrubicin and cisplatin combination against irinotecan and cisplatin in 284 patients; results were published online ahead of print on March 17 in the Journal of Clinical Oncology.”