ESMO Asia 2015 Press Release: Asian Women with Endocrine-Resistant Breast Cancer Benefit from Combination Therapy

“Data collected in Japanese and Korean patients included in the global PALOMA3 trial provides evidence that combining palbociclib with fulvestrant is an effective strategy to overcome endocrine resistance in women with hormone receptor positive (HR+), HER2 negative (HER2-) advanced breast cancer. The analysis of efficacy and safety of the combined therapy in an Asian population will be presented (1) at the first ESMO Asia 2015 Congress in Singapore, and results are in line with those reported in all patients (both Asian and non-Asian) earlier this year.

“Endocrine resistance is a major clinical issue that makes advanced breast cancer more difficult to treat. Hormone therapy is generally well tolerated and an easy-to-administer option for breast cancer, with demonstrated benefits in patients whose tumours express hormone receptors (HR), particularly the HR+/HER2- subgroup. The ideal option for patients is to be on one endocrine therapy after another, as long as the disease responds or remains unchanged. ‘However, unavoidably, resistance develops in almost all advanced patients a median ten months after the first-line hormonal agent is administered, and a much shorter median time after the second- or third-line hormonal agents, eventually driving patients to switch to the more toxic chemotherapy,’ one of the study authors, Dr. Jungsil Ro, Center for Breast Cancer at the National Cancer Center, Goyang, Korea, said.”


Motesanib Fails in a Phase III Trial for NSCLC

The gist: New research results have dashed hopes that a drug called motesanib (AMG 706) might be an effective treatment for Asian people with stage IV, non-squamous non-small cell lung cancer (NSCLC). In 2011, the drug failed testing in patients, but data showed there might be some benefit for certain Asian patients. Testing continued in a group of patients from Japan, South Korea, Taiwan, and Hong Kong. However, the new results show that motesanib does not improve standard treatment with the drugs paclitaxel and carboplatin.


For Certain Asian NSCLC Patients, Afatinib Is Better than Chemotherapy

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.’ ”


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.”


Boehringer Reports Data from Afatinib Phase III LUX-Lung 3 Trial in Asian NSCLC Patients

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.’ “


Ros1 Gene Fusions Found in 2.4% of Asian Patients with Lung Adenocarcinoma, Associated with Young Age at Diagnosis

The gist: Oncologists can sometimes look for certain genetic mutations in a patient’s tumor to help determine the best treatment options for that patient. Researchers have recently found that a particular mutation called ROS1 fusion is present in a subgroup of patients consisting of young East Asian patients with lung adenocarcinoma. People with ROS1 mutations in their lung tumors might benefit from treatment with a drug called crizotinib. The drug has not yet been approved for widespread use by the U.S. Food and Drug Administration (FDA), but patients can enroll in clinical trials to gain access to it.

“ROS1 fusion genes were successfully detected independent of gender or smoking history in young East Asian patients with lung adenocarcinoma, a histological subgroup in non-small cell lung cancer (NSCLC), using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) diagnostic tests.

“In NSCLC treatment algorithms, a personalized therapy approach is now being taken based on the genetic characteristics of the cancer. Patients with specific oncogenic molecular aberrations, for example EGFR mutations and ALK gene fusions, respond well to drugs that target these molecular abnormalities. ROS1 is another potential oncogenic molecular driver and this target is sensitive to crizotinib, a drug approved for the treatment of ALK gene fusion NSCLC .

“Researchers from the National Taiwan University Hospital examined 160 surgical specimens from early-stage and 332 specimens of fluid around the lungs (malignant pleural effusions) from late-stage lung adenocarcinoma patients. They initially examined these specimens for EGFR and KRAS mutations as well as ALK gene. Specimens that were negative for these three oncogenic drivers were then examined for ROS1 fusions using RT-PCR and IHC. Fluorescence in situ hybridization (FISH) was used if there was a discrepancy between RT-PCR and IHC.”


Rare Skin Cancer on Palms and Soles More Likely to Come Back Compared to Other Melanomas

“A rare type of melanoma that disproportionately attacks the palms and soles and under the nails of Asians, African-Americans, and Hispanics, who all generally have darker skins, and is not caused by sun exposure, is almost twice as likely to recur than other similar types of skin cancer, according to results of a study in 244 patients.

“The finding about acral lentiginous melanoma, as the potentially deadly cancer is known, is part of a study to be presented May 31 by researchers at the Perlmutter Cancer Center of NYU Langone at the annual meeting of the American Society of Clinical Oncology in Chicago.”


Motesanib Plus Carboplatin, Paclitaxel Extended Survival in NSCLC

“The addition of motesanib to carboplatin and paclitaxel improved OS, PFS and response rates in patients with nonsquamous non–small cell lung cancer, according to results of a phase 3 study.

“The subset analysis of the MONET1 trial included 227 Asian patients with stage IIIb/IV or recurrent disease who had not received prior systemic therapy for advanced NSCLC.”