Breast cancer is the most prevalent female neoplasm in Poland as well as in the rest of the world, accounting for 25% of all cancers. Lapatinib is a reversible inhibitor of the HER-1 and HER-2 tyrosine kinase receptors. Combined with capecitabine, it is administered in patients suffering from advanced breast cancer with HER-2 receptor overexpression. The present article analyses data obtained from medical records of 24 breast cancer patients treated with lapatinib and capecitabine in the years 2010–2015, in order to examine the treatment-related toxicity. The major adverse effects observed under treatment included diarrhoea, nausea, emesis, skin toxicity, and elevated transaminases. In 3 patients, grade 3 adverse events were reported, as assessed in accordance with CTCAE. The most frequent cause behind the cessation of treatment was disease progression. The analysis has indicated that lapatinib plus capecitabine is a well-tolerated treatment regimen.
The overexpression of the HER2 receptor and its gene amplification are observed in c. 20% of newly diagnosed cases of breast cancer and associated with a more aggressive clinical course and poorer prognosis. New HER2-targeted drugs, such as lapatinib, pertuzumab and trastuzumab emtansine, significantly improve patient outcomes. The article reviews the role of lapatinib in HER-targeted therapy and describes the treatment sequence of two women with HER2-positive advanced breast cancer.
The overexpression of the HER2 receptor and its gene amplification are observed in c. 20% of newly diagnosed cases of breast cancer and associated with a more aggressive clinical course and poorer prognosis. New HER2-targeted drugs, such as lapatinib, pertuzumab and trastuzumab emtansine, significantly improve patient outcomes. The article reviews the role of lapatinib in HER-targeted therapy and describes the treatment sequence of two women with HER2-positive advanced breast cancer.
HER2-positive breast cancer is associated with an aggressive clinical course and poor prognosis. At present, these patients may be offered targeted therapies directed against a specific molecular target, i.e. HER2 receptor. Standard agents of this class include trastuzumab (monoclonal antibody) and lapatinib (small-molecule inhibitor of HER2- receptor-associated tyrosine kinase). As estimated, about 25% of breast tumors are HER2-positive, and these patients are candidates for trastuzumab therapy. A precondition for initiation of the treatment is confirmation of overexpression of HER2 protein or amplification of HER2 gene in tumor cells. Trastuzumab administered as adjuvant treatment improves recurrence-free survival by 7% and overall survival by 3%. On the other hand, the same drug combined with chemotherapy in patients with disseminated breast cancer increases objective response rate, improves progression-free survival and overall survival as compared with chemotherapy alone. As estimated, only about 50% of HER2-positive patients obtained a clinical benefit following trastuzumab-based palliative treatment. There are several theories explaining the phenomenon of primary and secondary resistance to antibody-treatment. Patients previously undergoing with anthracycline- and taxoid-based chemotherapy, who experience recurrence or progression after trastuzumab, may benefit from administration of lapatinib, a HER1/HER2-associated small-molecule tyrosine kinase inhibitor, combined with capecitabine. Studies of novel therapeutic strategies in patients with HER2-positive breast cancer are underway, testing both new anti-HER2 antibodies (T-DM1, pertuzumab) and other small-molecule tyrosine kinase inhibitors (neratinib).
PL
HER2-dodatni rak piersi charakteryzuje się bardziej agresywnym przebiegiem i gorszym rokowaniem. W chwili obecnej istnieje możliwość zastosowania u tych chorych terapii ukierunkowanych na cel molekularny, jakim jest receptor HER2. Standardowo stosowanymi lekami tej grupy są przeciwciało monoklonalne trastuzumab i drobnocząsteczkowy inhibitor kinazy tyrozynowej receptorów HER2 i HER1 – lapatynib. Szacuje się, że około 25% guzów piersi jest HER2-pozytywnych – u tych chorych należy rozważyć wdrożenie terapii trastuzumabem. Warunkiem koniecznym rozpoczęcia leczenia jest wykazanie nadekspresji białka HER2 lub amplifikacji genu HER2 w komórkach nowotworowych. Trastuzumab stosowany w ramach leczenia uzupełniającego zwiększa przeżycie wolne od nawrotu o 7%, a przeżycie całkowite o 3%. Z kolei lek stosowany w skojarzeniu z chemioterapią u chorych z rozsianym rakiem piersi zwiększa odsetek obiektywnych odpowiedzi, wydłuża czas przeżycia wolny od progresji oraz czas przeżycia całkowitego w porównaniu z samą chemioterapią. Szacuje się, że tylko połowa chorych HER2-pozytywnych odnosi korzyść kliniczną z terapii paliatywnej opartej na trastuzumabie. Istnieje kilka teorii tłumaczących zjawisko pierwotnej i wtórnej oporności na leczenie przeciwciałem. U chorych leczonych wcześniej chemioterapią opartą na antracyklinach i taksoidach, u których dochodzi do nawrotu lub progresji po leczeniu trastuzumabem, można zastosować drobnocząsteczkowy inhibitor kinaz tyrozynowych HER1/HER2 – lapatynib w skojarzeniu z kapecytabiną. Obecnie trwają badania nad nowymi strategiami terapeutycznymi u chorych z HER2-pozytywnym rakiem piersi. Są to zarówno nowe przeciwciała „anty-HER2” (T-DM1, pertuzumab), jak i kolejne drobnocząsteczkowe inhibitory kinaz tyrozynowych (neratynib).
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