Intensive adjuvant therapy for early breast cancer with positive HER2

Puma biotechnology is a biopharmaceutical company focused on developing and commercializing innovative products to enhance cancer care Recently, the company announced that its authorized partner, specialized therapeutics Asia (STA), has received marketing approval from the Singapore Health Sciences Agency (HSA) for the targeted anticancer drug nerlynx (naratinib) in Singapore, six months ahead of schedule Nerlynx is suitable for the intensive adjuvant treatment of early breast cancer patients with HER2 overexpression / amplification after trastuzumab adjuvant treatment It is worth mentioning that in early November, nerlynx, puma's authorized partner in Greater China, Beihai Kangcheng Pharmaceutical Co., Ltd (Beihai Kangcheng), announced that nerlynx was approved to be listed in Hong Kong This is the first time nerlynx has been approved in Greater China, and it is also the first cancer targeted treatment drug of Beihai Kangcheng Beihai Kangcheng signed nerlynx's exclusive license agreement in Greater China with puma company in January 2018 In September of the same year, it submitted a new drug listing application to China National Drug Administration (nmpa) and was officially accepted The indications are: it is used for the intensive adjuvant treatment of trastuzumab in the early breast cancer patients with HER2 positive It is estimated that about 20-25% of breast cancer tumors overexpress HER2 protein HER2 positive breast cancer is more aggressive than other types of breast cancer, increasing the risk of disease progression and death Although studies have shown that trastuzumab can reduce the risk of postoperative recurrence of early HER2 positive breast cancer, 25% of patients still relapse after trastuzumab treatment Patients with recurrent and metastatic HER2 positive breast cancer are usually incurable The location of metastasis includes contralateral breast, brain, lung, bone and so on Brain metastasis is one of the main causes of death According to the patient registration system of Hong Kong Hospital, 4391 new breast cancer patients were added in Hong Kong in 2017, and it is estimated that 20-25% of them are HER2 positive According to Singapore health data, breast cancer is the most common cancer affecting women in Singapore, accounting for almost 30% of all cancer cases It is estimated that one out of every 15 women is diagnosed with breast cancer by the age of 75 At present, in clinical, the effective treatment of tumor has always been surgical resection, except for surgery, the treatment is called auxiliary treatment, its purpose is to eliminate the remaining small metastasis, reduce the chance of tumor recurrence and metastasis, and improve the cure rate The launch of nerlynx will provide a new and important treatment option for women with breast cancer, and reduce the risk of recurrence of HER2 positive breast cancer Nerlynx is an oral, powerful, irreversible tyrosine kinase inhibitor (TKI), which inhibits tumor growth and metastasis by blocking the pan her family (HER1, HER2, HER4) and downstream signaling pathways The mechanism of action of the drug is different from that of roxithine (trastuzumab) and perjeta (patozumab), the new breast cancer drug The latter two drugs are monoclonal antibody drugs, targeting the HER2 receptor on the surface of HER2 positive cancer cells In July 2017, nerlynx was first approved by the US FDA for intensive adjuvant therapy of trastuzumab in adult patients with HER2 positive early breast cancer In September 2018, nerlynx received EU approval for intensive adjuvant therapy for early breast cancer patients with hormone receptor positive (HR +) and HER2 positive In terms of medication, the recommended dose of nerlynx is 240mg (6 tablets 40mg), which is taken orally once a day, together with food, for one year It should be noted that anti diarrhea preventive treatment should be initiated at the first administration of nerlynx and continued in the first two treatment cycles (56 days), and then anti diarrhea preventive treatment can be continued if necessary to prevent drug-induced diarrhea The HSA approval of nerlynx is based on data from the phase III clinical trial extenet The study was a multicenter, randomized, double-blind, placebo-controlled study that evaluated the use of nerlynx in extended adjuvant therapy after trastuzumab In this study, women with early HER2 positive breast cancer (n = 2840) within two years after completion of adjuvant therapy with trastuzumab were randomly treated with nerlynx (n = 1420) or placebo (n = 1420) for one year Patients with recurrent disease, intraductal carcinoma in situ (DCIS) or death were followed up for 5 years after randomization The primary end point was noninvasive disease survival (IDFs) The results showed that during a median follow-up of 5.2 years, nerlynx treatment significantly reduced the risk of recurrence or death of invasive disease by 27% compared with placebo (HR = 0.73, P = 0.008) The 5-year noninvasive disease survival rate (IDFs) of nerlynx group was 90.2%, and that of placebo group was 87.7% Another 5-year subgroup analysis showed that among hormone receptor positive (HR +) breast cancer patients who started nerlynx therapy within 12 months after trastuzumab treatment, the greatest benefit was observed: a 42% reduction in the risk of recurrence in 5 years In the study, diarrhea was the most common side effect leading to discontinuation Puma is conducting a phase II control study to investigate various prophylactic anti diarrhea regimens for the first 1-2 cycles of nerlynx treatment New data show that prophylactic treatment reduces the incidence, severity, and duration of nerlynx associated diarrhea compared to observed overall events.