Abstract:
This analysis of the RASH trial (NCT01729481) aimed at gaining a better understanding of the \"Burden of Therapy\" (BOTh®TM) in pancreatic ductal adenocarcinoma (PDAC). In the RASH study, 150 patients with newly diagnosed metastatic PDAC were treated with gemcitabine plus erlotinib (gem/erlotinib) for four weeks. Patients who developed a skin rash during this four-week run-in phase continued with the gem/erlotinib treatment, while rash-negative patients were switched to FOLFIRINOX. The study demonstrated a 1-year survival rate of rash-positive patients who received gem/erlotinib as first-line treatment that was comparable to previous reports of patients receiving FOLFIRINOX. To understand whether these comparable survival rates may be accompanied by better tolerability of the gem/erlotinib treatment compared to FOLFIRINOX, the BOTh®TM methodology was used to continuously quantify and depict the burden of therapy generated by treatment emergent events (TEAEs). Sensory neuropathy was significantly more common in the FOLFIRINOX arm, and prevalence as well as severity increased over time. In both arms, the BOTh®TM associated with diarrhea decreased over the course of treatment. The BOTh®TM caused by neutropenia was comparable in both arms but decreased in the FOLFIRINOX arm over time, possibly due to chemotherapy dose reductions. Overall, gem/erlotinib was associated with a slightly higher overall BOTh®TM, but the difference was not statistically significant (p = 0.6735). In summary, the BOTh®TM analysis facilitates the evaluation of TEAEs. In patients fit for intense chemotherapeutic regimens, FOLFIRINOX is associated with a lower BOTh®TM than gem/erlotinib.
摘要:
对RASH试验(NCT01729481)的分析旨在更好地了解胰腺导管腺癌(PDAC)的“治疗负担”(BOTh®TM)。在RASH研究中,150例新诊断的转移性PDAC患者接受吉西他滨加厄洛替尼(gem/erlotinib)治疗4周。在这四周磨合期出现皮疹的患者继续使用gem/erlotinib治疗,而皮疹阴性患者改用FOLFIRINOX。该研究表明,接受gem/erlotinib作为一线治疗的皮疹阳性患者的1年生存率与以前接受FOLFIRINOX的患者报告相当。为了了解这些可比较的生存率是否伴随着与FOLFIRINOX相比更好的gem/erlotinib治疗耐受性,BOTh®TM方法学用于连续量化和描述由治疗突发事件(TEAE)产生的治疗负担.感觉神经病在FOLFIRINOX臂中明显更常见,患病率和严重程度随着时间的推移而增加。在双臂中,与腹泻相关的BOTh®TM在治疗过程中下降。由中性粒细胞减少症引起的BOTh®TM在两组中相当,但随着时间的推移,FOLFIRINOX组下降,可能是由于化疗剂量减少。总的来说,宝石/厄洛替尼与整体BOTh®TM略高相关,但差异无统计学意义(p=0.6735)。总之,BOTh®TM分析有助于TEAE的评估。在适合强烈化疗方案的患者中,FOLFIRINOX与比宝石/厄洛替尼更低的BOTh®TM相关。