Which intervention works for whom: Identifying pre-treatment characteristics that predict who will benefit from a specific alcohol text message intervention from a randomized trial

Article

作者: Suffoletto, Brian ; Bhurosy, Trishnee ; Chung, Tammy

INTRODUCTIONEffective interventions show heterogeneity in treatment response. Addressing this heterogeneity involves identifying which intervention works best for whom. One method to address this heterogeneity identifies treatment-subgroup interactions to determine which of two interventions has greater effect for certain individuals based on their profile of pre-treatment characteristics. This secondary analysis of a randomized clinical trial (RCT) to address binge drinking examined whether two of the RCT's interventions, GOAL and COMBO, which produced similar reductions in drinking outcomes, might have involved treatment-subgroup interactions. Identifying treatment-subgroup interactions can inform efficient patient-treatment matching that optimizes individual outcomes.METHODSThese secondary analyses included young adults (n = 344; 68.6 % female, ages 18-25) randomized to GOAL or COMBO 12-week alcohol text message interventions and who completed 3-month follow-up (end of intervention). GOAL provided weekly support for drinking limit goals. COMBO included all GOAL features, in addition to pre-event feedback on drinking plans and post-event feedback on alcohol consumption. QUINT, a tree-based algorithm, aimed to identify treatment-subgroup interactions using 21 pre-treatment (baseline) characteristics (e.g., demographics, perceived risk of binge-drinking related harm, perceived number of peers drinking to intoxication) that predicted the primary outcome of binge drinking at follow-up.RESULTSThe algorithm used five pre-treatment characteristics (sex, race, perceived risk of binge drinking-related harm, perceived number of peers drinking to intoxication, and any cannabis use in the past 3 months) to identify 7 treatment-subgroup interactions. COMBO had greater effectiveness than GOAL, for example, for females who reported lower risk of binge-drinking related harm and no cannabis use in the past 3 months, whereas GOAL had greater effectiveness for females who reported higher risk of binge-drinking related harm and more peers who drank to intoxication. In comparison, GOAL had greater effectiveness than COMBO among White males, whereas males of other racial backgrounds benefitted more from COMBO than GOAL.CONCLUSIONSThe identified treatment-subgroup interactions involving GOAL and COMBO indicated which intervention had greater effectiveness for which subgroups of individuals based on pre-treatment characteristics. These findings can help efficiently match individuals to effective interventions, bringing the field closer to personalized, precision care.CLINICAL TRIALS REGISTRATION NUMBERNCT02918565.

2024-03-01·European Journal of Cancer

Combined immunotherapy in melanoma patients with brain metastases: A multicenter international study

Article

作者: Couselo, Eva Munoz ; Giannarelli, Diana ; Quaglino, Pietro ; Del Vecchio, Michele ; da Silva, Ines Pires ; Sergi, Maria Chiara ; Occelli, Marcella ; Long, Georgina V ; Benannoune, Naima ; Di Giacomo, Anna Maria ; Robert, Caroline ; Indini, Alice ; Rutkowski, Piotr ; Tucci, Marco ; Spagnolo, Francesco ; Guida, Michele ; Merelli, Barbara ; Neyns, Bart ; Lorigan, Paul ; Ascierto, Paolo A ; Rossi, Ernesto ; Placzke, Joanna ; Depenni, Roberta ; Arance, Ana Maria ; Queirolo, Paola ; Serra, Patricio ; Vitale, Maria Grazia ; Menzies, Alexander M ; Mandalà, Mario

BACKGROUNDIpilimumab plus nivolumab (COMBO) is the standard treatment in asymptomatic patients with melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO outside clinical trials.METHODSConsecutive patients treated with COMBO have been included. Demographics, steroid treatment, Central Nervous System (CNS)-related symptoms, BRAF status, radiotherapy or surgery, response rate (RR), progression-free (PFS) and overall survival (OS) have been analyzed.RESULTS376 patients were included: 262 received COMBO as first-line and 114 as a subsequent line of therapy, respectively. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) (≥1 vs 0) [HR 1.97 (1.46-2.66)], extracerebral metastases [HR 1.92 (1.09-3.40)], steroid use at the start of COMBO [HR 1.59 (1.08-2.38)], CNS-related symptoms [HR 1.59 (1.08-2.34)], SRS (Stereotactic radiosurgery) [HR 0.63 (0.45-0.88)] and surgery [HR 0.63 (0.43-0.91)] were associated with OS. At a median follow-up of 30 months, the median OS (mOS) in the overall population was 21.3 months (18.1-24.5), whilst OS was not yet reached in treatment-naive patients, steroid-free at baseline. In patients receiving COMBO after BRAF/MEK inhibitors(i) PFS at 1-year was 15.7%. The dose of steroids (dexamethasone < vs ≥ 4 mg/day) was not prognostic. SRS alongside COMBO vs COMBO alone in asymptomatic patients prolonged survival. (p = 0.013). Toxicities were consistent with previous studies. An independent validation cohort (n = 51) confirmed the findings.CONCLUSIONSOur results demonstrate remarkable long-term survival in treatment-naïve, asymptomatic, steroid-free patients, as well as in those receiving SRS plus COMBO. PFS and OS were poor in patients receiving COMBO after progressing to BRAF/MEKi.

2024-02-01·Bioorganic Chemistry

Novel GSH-responsive prodrugs derived from indole-chalcone and camptothecin trigger apoptosis and autophagy in colon cancer

Article

作者: Nie, Caiyun ; Chen, Xiaobing ; Wang, Jianzheng ; Chen, Beibei ; Bai, Qiwen ; Xu, Weifeng ; Wang, Saiqi ; Luo, Miao ; Lv, Huifang ; Wang, Hui ; Yao, Zhentao

Antineoplastic agents that target tubulin have shown efficacy as chemotherapeutic drugs, yet they are often constrained by multidrug resistance (MDR) and unwanted side effects. A multi-targeted strategy demonstrates great potency in reducing toxicity and enhancing efficacy and provides an alternative way for attenuating MDR. In this study, a series of dual-targeted anti-cancer agents based on indole-chalcone derivatives and the camptothecin (CPT) scaffold were synthesized. Among them, 14-1 demonstrated superior anti-proliferative activity than its precursor 13-1, CPT or their physical mixtures against tested cancer cells, including multidrug-resistant variants, while exhibited moderate cytotoxicity toward human normal cells. Mechanistic studies revealed that 14-1 acted as a glutathione-responsive prodrug, inducing apoptosis by substantially enhancing intracellular uptake of CPT, inhibiting tubulin polymerization, increasing the accumulation of intracellular reactive oxygen species, and initiating a mitochondrion-dependent apoptotic pathway. Moreover, 14-1 notably induced autophagy and suppressed topoisomerase I activity to further promote apoptosis. Importantly, 14-1 displayed potent inhibitory effect on tumor growth in paclitaxel (PTX)-resistant colorectal cancer (HCT-116/PTX) xenograft models without inducing obvious toxicity compared with CPT- or combo-treated group. These results suggest that 14-1 holds promise as a novel candidate for anti-cancer therapy, particularly in PTX-resistant cancers.

100 项与 combo (EndoCeutics) 相关的药物交易

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