Patients\u00a0with\u00a0leptomeningeal\u00a0metastasis\u00a0(LM)\u00a0have historically had\u00a0few\u00a0treatment\u00a0options. Now, researchers from\u00a0The University of Texas MD\u202fAnderson Cancer Center\u00a0have found a\u00a0combination of\u00a0targeted therapies,\u00a0tucatinib\u00a0and\u00a0trastuzumab,\u00a0plus\u00a0the\u00a0chemotherapy drug,\u00a0capecitabine,\u00a0may improve\u00a0symptoms and\u00a0extend survival in\u00a0some\u00a0breast cancer\u00a0patients\u00a0with LM.\u00a0<\/p>\n
The Phase II\u00a0study, published today in\u00a0Nature\u00a0Cancer,\u00a0included\u00a017 female patients\u00a0with\u00a0newly diagnosed LM and HER2+\u00a0breast cancer.\u00a0Median overall survival\u00a0(OS)\u00a0in those treated with\u00a0the\u00a0combination\u00a0therapy\u00a0increased from\u00a0a\u00a0historical\u00a0average of 4.4 months to 10 months. At the\u00a018-month\u00a0mark,\u00a041% of patients\u00a0were still alive.\u00a0Under the\u00a0combination\u00a0treatment, disease progression also stalled, with a median\u00a0of\u00a0seven\u00a0months\u00a0before central nervous system<\/a> progression, and\u00a0seven of 12 evaluable patients\u00a0also had\u00a0improved neurologic deficits.\u00a0<\/p>\n
<\/p>\n The combination achieved a clinically meaningful improvement in overall survival compared to historical controls. For\u00a0these\u00a0patients,\u00a0who often face limited treatment options,\u00a0our\u00a0results represent\u00a0a\u00a0step forward,\u00a0offering new hope in how we treat and manage\u00a0leptomeningeal metastasis<\/a>.”\u00a0<\/p>\n
Rashmi Murthy, M.D., lead author, associate professor of\u00a0Breast Medical Oncology<\/p>\n
<\/p>\n Why\u00a0are\u00a0there limited treatments for\u00a0patients\u00a0with leptomeningeal metastasis?\u00a0<\/p>\n Leptomeningeal metastasis\u00a0is difficult to treat\u00a0primarily\u00a0because the blood-brain barrier may block\u00a0drugs from reaching the spinal fluid,\u00a0where the\u00a0metastatic\u00a0cells\u00a0are\u00a0found. Additionally, LM is not\u00a0a\u00a0solid\u00a0tumor but\u00a0is\u00a0made up of\u00a0metastatic cells\u00a0living in fluid, making\u00a0them\u00a0more difficult to target.\u00a0Historically, there\u00a0also\u00a0are\u00a0few studies about\u00a0this\u00a0specific\u00a0disease.\u00a0<\/p>\n “In addition to encouraging survival outcomes,\u00a0throughout this study we\u00a0observed improvements in neurologic symptoms,”\u00a0said co-lead author\u00a0Barbara O’Brien, M.D., associate professor of\u00a0Neuro-Oncology.\u00a0“Treatments for breast cancer leptomeningeal metastasis have historically focused on stabilizing disease rather than improving symptoms, making these\u00a0findings particularly meaningful and encouraging.”\u00a0<\/p>\n How\u00a0do the treatments\u00a0in this combination\u00a0therapy\u00a0work?\u00a0<\/p>\n Tucatinib is a\u00a0targeted therapy\u00a0pill that blocks\u00a0the HER2\u00a0protein, which helps some breast\u00a0cancers\u00a0grow.\u00a0Trastuzumab is a targeted antibody\u00a0that attaches to the HER2 protein on cancer cells and helps the immune system destroy them.\u00a0Finally,\u00a0capecitabine is a chemotherapy pill that turns into 5-fluorouracil (5-FU) in the body\u00a0to\u00a0eliminate\u00a0fast-growing cancer cells.\u00a0<\/p>\n The single arm,\u00a0non-randomized,\u00a0multi-phase study\u00a0enrolled\u00a0patients\u00a0at four sites in the\u00a0U.S., including UT MD Anderson. Eligible patients were\u00a0at\u00a0least 18\u00a0years\u00a0old\u00a0with histologically proven metastatic HER2+ breast carcinoma.\u00a0These\u00a0patients\u00a0were treated with 21-day cycles of oral tucatinib (300 mg) twice daily, plus oral capecitabine (1000 mg\/m2) twice daily on\u00a0days\u00a01-14 and intravenous trastuzumab (6 mg\/kg) on\u00a0day 21.\u00a0<\/p>\n What\u00a0are\u00a0other\u00a0key\u00a0findings of the study?\u00a0<\/p>\n Side effects included\u00a0diarrhea, nausea, vomiting, hand-foot syndrome, and liver function test elevation.\u00a0Most\u00a0adverse effects\u00a0improved or resolved with\u00a0appropriate care\u00a0and dose modifications.\u00a0One patient saw alanine aminotransferase elevation after one cycle, which led to discontinuation\u00a0of the combination,\u00a0and\u00a0symptoms\u00a0resolved after one month.\u00a0<\/p>\n Study limitations include early termination due to slow accrual following\u00a0Food & Drug Administration (FDA)\u00a0approval of the\u00a0combination\u00a0therapy. Additionally, LM from HER2+\u00a0metastatic breast cancer<\/a>\u00a0is\u00a0rare, resulting in limited published data. As a result, the study design was informed by the small amount of available retrospective evidence.<\/p>\n Source:<\/p>\n University of Texas M. D. Anderson Cancer Center<\/a><\/p>\n Journal reference:<\/p>\n
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