Patients with triple-negative breast cancer (TNBC) and residual invasive disease (RD) after completion of neoadjuvant chemotherapy (NAC) have a high-risk for recurrence, which is reduced by adjuvant ...capecitabine. Preclinical models support the use of platinum agents in the TNBC basal subtype. The EA1131 trial hypothesized that invasive disease-free survival (iDFS) would not be inferior but improved in patients with basal subtype TNBC treated with adjuvant platinum compared with capecitabine.
Patients with clinical stage II or III TNBC with ≥ 1 cm RD in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine 14 out of 21 days every 3 weeks for six cycles. TNBC subtype (basal
nonbasal) was determined by PAM50 in the residual disease. A noninferiority design with superiority alternative was chosen, assuming a 4-year iDFS of 67% with capecitabine.
Four hundred ten of planned 775 participants were randomly assigned to platinum or capecitabine between 2015 and 2021. After median follow-up of 20 months and 120 iDFS events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year iDFS for platinum was 42% (95% CI, 30 to 53) versus 49% (95% CI, 39 to 59) for capecitabine. Grade 3 and 4 toxicities were more common with platinum agents. The Data and Safety Monitoring Committee recommended stopping the trial as it was unlikely that further follow-up would show noninferiority or superiority of platinum.
Platinum agents do not improve outcomes in patients with basal subtype TNBC RD post-NAC and are associated with more severe toxicity when compared with capecitabine. Participants had a lower than expected 3-year iDFS regardless of study treatment, highlighting the need for better therapies in this high-risk population.
BackgroundHuman immunodeficiency virus type 1 (HIV-1) elite controllers are able to control virus replication to levels below the limits of detection by commercial assays, but the actual level of ...viremia in these individuals is not well defined. Here, we quantify plasma HIV-1 RNA in elite controllers and correlate this with specific immunologic parameters MethodsPlasma HIV-1 RNA levels were quantified in 90 elite controllers with use of a real time reverse-transcriptase polymerase chain reaction assay with a sensitivity of 0.2 copies/mL. HIV-1–specific immune responses and longitudinal CD4+ T cell counts were examined ResultsThe median plasma HIV-1 RNA level was 2 copies/mL (interquartile range, 0.2–14 copies/mL). A longitudinal analysis of 31 elite controllers demonstrated 2–5–fold fluctuations in viremia in the majority of individuals; 6 had persistent levels below 1 copy/mL. Viremia correlated directly with HIV-1–specific neutralizing antibodies and Western blot reactivity but not with CD8+ T cell responses. Absolute CD4+ T cell decrease was more common among individuals with detectable viremia (P=.04) ConclusionsLow-level viremia is present in the majority of elite controllers and is associated with higher HIV-1–specific antibody responses. Absolute CD4+ T cell loss is more common among viremic individuals, suggesting that even very low-level viremia has negative consequences over time
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