RESUMO
Gastric cancer is one of the most common malignancy worldwide with a prognosis less than 1 year in unresectable or metastatic disease. HER2 expression is the main biomarker to lead the addition of trastuzumab to first line systemic chemotherapy improving the overall survival in advanced HER2-positivegastric adenocarcinoma. The inevitable development of resistance to trastuzumab remains a great problem inasmuch several treatment strategies that have proven effective in breast cancer failed to show clinical benefit in advanced gastric cancer. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance toHER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Further, we describe the prognostic value of new non-invasive screening techniques, the current development of novel agents such us HER2 antibody-drug conjugates and bispecific antibodies, and the strategies with antitumor activity on going.
Assuntos
Adenocarcinoma , Imunoconjugados , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Humanos , Imunoconjugados/uso terapêutico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Trastuzumab/uso terapêuticoRESUMO
BACKGROUND: Novel hormonal therapies have been recently investigated in non-metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the efficacy and safety of novel hormonal therapies in non-metastatic CRPC. MATERIALS AND METHODS: The primary outcome was metastasis-free survival (MFS). The secondary endpoints were overall survival (OS), time to PSA progression and safety. We planned a subgroup analysis according to the PSA doubling time (> 6 vs < 6 months), Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0) and concomitant use of bone-targeting agent (yes vs no). RESULTS: Pooled analysis of novel hormonal therapies revealed significantly increased MFS compared with placebo (hazard ratio (HR): HR = 0.32, 95% CI 0.25-0.41; p < 0.00001). The subgroup analysis showed a statistically significant MFS advantage in favour of men with the lower ECOG performance status. Other secondary endpoints favoured the novel hormonal therapies. The relative risk (RR) of grade ≥ 3 adverse events and ≥ 3 hypertension was 1.31 and 1.39, respectively. CONCLUSIONS: This study confirmed the efficacy and safety of the novel hormonal therapies in non-metastatic CRPC.