Socio-economic factors and ethical dilemmas in personalized medicine provision
Shirley Sun in Socio-economics of Personalized Medicine in Asia, 2016
Drugs on the SDL II list are subsidized at a rate between 50 and 75 percent of their retail cost (Ministry of Health, 2012). To qualify for the higher 75 percent subsidy, however, patients must come from a low-income family, earning no more than a monthly SGD$1,500 household per capita income (Ministry of Health, 2012). Of the 18 personalized drugs listed in HSA’s database, only two are on the SDL. They are trastuzumab (known as Herceptin) and letrozole (known as Femara) (Ministry of Health, 2015). The remaining 16 drugs, however, may be covered under the Medication Assistant Fund (MAF). The MAF subsidizes expensive drugs that have not been included on the SDL, but are deemed necessary to treat patients (Ministry of Health, 2012). Indeed, in response to a query made concerning the availability and cost of afatinib, a personalized drug used to treat non-small-cell lung cancer with an EGFR mutation, the National Cancer Centre noted that, though the drug is not currently on the SDL, the MAF could be extended to cover it (Toh, 2014).
Biologically Targeted Agents in Head and Neck Cancers
John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford in Head & Neck Surgery Plastic Surgery, 2018
Afatinib has been assessed in the phase III LUX head and neck-1 study in patients receiving second-line therapy for relapsed/metastatic SCCHN.55 A total of 583 patients were treated with afatinib (322 patients) or methotrexate (161 patients). Afatinib significantly increased median progression-free survival (2.6 vs. 1.7 months, p = 0.03) but did not improve median overall survival (6.8 vs 6.0 months) relative to methotrexate. The overall response rates of the two study arms were low—10.2% and 5.6%, respectively. In an integrated analysis of quality of life, afatinib showed a delay in deterioration of global health status, pain and swallowing problems (all p ≤ 0.03). The profile of toxicities was markedly different between the two treatments, with afatinib causing more rash and diarrhoea and methotrexate causing more stomatitis and leukopenia. A randomized phase II comparison of afatinib and cetuximab has also demonstrated that afatinib has similar antitumour activity to cetuximab, as assessed by tumour shrinkage on treatment.56 It remains to be seen if, on the basis of these data, afatinib finds a place in the treatment process for patients with relapsed/metastatic SCCHN.
Oral Mucosal Reactions to Anticancer Therapies
Gabriella Fabbrocini, Mario E. Lacouture, Antonella Tosti in Dermatologic Reactions to Cancer Therapies, 2019
Pan-HER tyrosine kinase inhibitors: Conversely, with the new generation of pan-HER tyrosine kinase inhibitors, mucositis appears to be one of the main toxicities, after paronychia, diarrhea, and papulopustular rash (52). The incidence of all-grade mucositis induced by afatinib appears to be significantly higher than that of erlotinib or gefitinib, and ranges from 29 to 64%. All-grade incidence reported with dacomitinib appears to be very similar to afatinib (about 40%). Finally, high-grade (≥3) mucositis induced by afatinib and dacomitinib may occur in 3–7% of treated patients (4).
Targeting the EGFR signaling pathway in cancer therapy: What’s new in 2023?
Published in Expert Opinion on Therapeutic Targets, 2023
Sushanta Halder, Soumi Basu, Shobhit P. Lall, Apar K. Ganti, Surinder K. Batra, Parthasarathy Seshacharyulu
Afatinib (BIBW 2992/Gilotrif): Afatinib is an orally active anilino-quinazoline derivative EGFR-TKI which binds and inhibits selectively and irreversibly to EGFR, HER2, and HER4. It was approved by the US FDA and European Medical Agency (EMA) in 2013 to treat advanced metastatic EGFR mutation harboring NSCLC [73]. This is also under investigation as monotherapy to treat HER2-positive breast cancer patients who have progressed to trastuzumab [74]. Our group has extensively investigated the effect of afatinib on multiple cancers. Recently, we found a synergistic effect of afatinib with gemcitabine in reducing pancreatic cancer (PC) progression and metastasis by impeding cancer stem cell (CSC) growth using preclinical organoid and mouse models [17]. Afatinib has a synergistic effect with temozolomide in inhibiting the growth, proliferation, and tumorigenesis ability of glioblastoma cells modulated to express EGFR (wild type), mutant EGFRvIII, and EGFR dead kinase [75]. Furthermore, our group demonstrated afatinib’s anti-proliferation, migration, and anti-survival action in pancreatic cancer cells [16]. We have also reported that afatinib shows an anti-tumorigenic effect and radio-sensitizes head and neck squamous cell carcinoma (HNSCC) cells by eradicating the CSC population [18].
Four generations of EGFR TKIs associated with different pathogenic mutations in non-small cell lung carcinoma
Published in Journal of Drug Targeting, 2020
Rui Li, Xiaofei Zhou, Hongjuan Yao, Liang Li
Researchers conducting the LUX-Lung7 [55] clinical trial compared the efficacy of afatinib and gefitinib as first-line treatment for patients with advanced NSCLC carrying EGFR mutations. Afatinib prolonged PFS more than gefitinib (11.0 vs. 10.9 months), and reduced the risk of lung cancer progression and treatment failure by 27%; however, compared to first-generation EGFR TKIs, second-generation drugs often have dose-limiting toxicities, such as rash, acne, stomatitis, and diarrhoea [56]. Recent in vitro studies demonstrated that afatinib could inhibit the growth of T790M mutant NSCLC cells [57]. Yap et al. [58] determined the dose-limiting toxicity and maximum tolerated dose of afatinib, and concluded that afatinib was well-tolerated in patients with advanced disease. Besides, they confirm the results of previous in vitro experiments in which afatinib inhibited the growth of solid tumours with T790M mutations. In another clinical study [59], afatinib combined with cetuximab was used to treat NSCLC patients with EGFR mutations who had become resistant to gefitinib or erlotinib. This therapeutic combination achieved durable and significant clinical responses with an acceptable safety profile, regardless of T790M mutational status.
Heterogeneous clinical and pathological landscapes of HER2 positive colorectal cancer
Published in Expert Review of Anticancer Therapy, 2021
Zhiqin Chen, Jinde Chen, Yong Gao, Ming Quan
Clinical trial shows that lung cancer patients with HER2 mutations have benefited from Afatinib (an irreversible EGFR/HER2 inhibitor) [39]. Afatinib can also inhibit tumor cell growth and promote apoptosis in HER2 overexpressing CRC cells in vitro and vivo [40]. It is noteworthy that BRAFwt -microsatellite instability (MSI) CRC has a higher frequency of HER2 mutations, notably with regard to the common L755S and V842I substitutions. The authors demonstrated that HER2-mutated MSI CRC cells were susceptible to afatinib and neratinib [41]. In addition, complementary medicine has also provided a novel mechanism including the ability of simvastatin to significantly abrogate HER2-induced tumors angiogenesis by impeding VEGF secretion [42]. The findings suggested that simvastatin can remodel the abnormal tumor vasculature to improve current treatment.
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