RESUMEN
This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1-7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.
RESUMEN
The effects of high salt intake on blood pressure and renal function were studied in nine subtotally nephrectomized pregnant ewes (STNxP) and seven intact pregnant ewes (IntP) in late gestation and in eight subtotally nephrectomized nonpregnant ewes (STNxNP) and seven intact nonpregnant ewes (IntNP). STNxP had higher mean arterial pressures (P < 0.02) and plasma creatinine levels (P < 0.001) than IntP. High salt (0.17 M NaCl as drinking water for 5 days) did not change blood pressure in either STNxP or IntP. STNxNP had higher mean arterial pressures (P = 0.03) and plasma creatinine levels (P < 0.001) than IntNP. In STNxNP, blood pressure increased with high salt intake and there was a positive relationship between diastolic pressure and sodium balance (r = 0.497, P = 0.05). This relationship was not present in IntNP, STNxP, or IntP. Because high salt intake did not cause an increase in blood pressure in STNxP, it is concluded that they were protected by pregnancy from further rises in blood pressure. The observed increase in glomerular filtration rate (P < 0.03) and depression of fractional proximal sodium reabsorption (P = 0.003) that occurred in STNxP, but not in STNxNP, in response to high salt may have contributed to this protection. As well, the increased production of vasorelaxants in pregnancy may selectively protect against the occurrence of salt-sensitive hypertension in pregnancy.