Le Xiuning, Gleber-Netto Frederico O, Rubin M Laura, Qing Yun, Du Robyn, Kies Merrill, Blumenschein George, Lu Charles, Johnson Faye M, Bell Diana, Lewis Jeff, Zhang Jiexin, Feng Lei, Wilson Kaye, Marcelo-Lewis Kathrina, Wang Jing, Ginsberg Lawrence, Gillison Maura, Lee J Jack, Meric-Bernstam Funda, Mills Gordon B, William William N, Myers Jeffrey N, Pickering Curtis R
The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
The University of Texa MD Anderson Cancer Center, Houston, TX, United States.
Clin Cancer Res. 2022 Apr 20. doi: 10.1158/1078-0432.CCR-21-3239.
Neoadjuvant chemotherapy prior to definitive surgery has been utilized widely for locally advanced oral squamous cell carcinoma (OSCC). We evaluated neoadjuvant erlotinib with platinum-docetaxel vs. placebo with platinum-docetaxel in stage III-IVB OSCC patients.
Patients with newly diagnosed stage III, IVA, IVB (AJCC 7th) OSCC amenable to surgical resection were included. Patients were randomized to receive up to 3 cycles of chemotherapy with concurrent erlotinib or placebo, followed by surgery. The primary endpoint was major pathologic response (MPR) rate, secondary endpoints included safety, overall (OS) and progression-free survival (PFS).
Fifty-two patients received at least one cycle of treatment and 47 were evaluable with surgical resection. MPR rate was not different between erlotinib (30%, 7/23) and placebo arms (41.7%, 10/24) (p=0.55). At median follow up of 26.5 months, there was no difference on OS or PFS between groups. Patients who received erlotinib with chemotherapy and achieved MPR (n=7) had no recurrence. The treatment-related adverse event rates were not different between the two groups (96% vs. 96%). However, rash, mostly low grade, was more common in the erlotinib arm (79% vs. 50%). Transcriptomic analysis in the pre-treatment samples indicated that genes in protein glycosylation and Wnt signaling pathways were associated with benefit in those treated with erlotinib plus chemotherapy.
The addition of erlotinib to platinum-taxane chemotherapy was well-tolerated but did not induce higher rates of MPR or PFS or OS survival benefit. Patients who received chemotherapy with erlotinib and achieved major pathological responses had excellent clinical outcome.
对于局部晚期口腔鳞状细胞癌（OSCC），在确定性手术前广泛应用新辅助化疗。我们评估了在Ⅲ - ⅣB期OSCC患者中，新辅助使用厄洛替尼联合铂 - 多西他赛与使用安慰剂联合铂 - 多西他赛的疗效。
纳入新诊断的、适合手术切除的Ⅲ期、ⅣA期、ⅣB期（美国癌症联合委员会第7版）OSCC患者。患者被随机分配接受最多3个周期的化疗，同时使用厄洛替尼或安慰剂，随后进行手术。主要终点是主要病理缓解（MPR）率，次要终点包括安全性、总生存期（OS）和无进展生存期（PFS）。
52例患者接受了至少一个周期的治疗，47例可进行手术切除评估。厄洛替尼组（30%，7/23）和安慰剂组（41.7%，10/24）的MPR率无差异（p = 0.55）。在中位随访26.5个月时，两组之间的OS或PFS无差异。接受厄洛替尼联合化疗并达到MPR的患者（n = 7）无复发。两组的治疗相关不良事件发生率无差异（96%对96%）。然而，皮疹（大多为低级别）在厄洛替尼组更常见（79%对50%）。治疗前样本的转录组分析表明，蛋白质糖基化和Wnt信号通路中的基因与接受厄洛替尼加化疗的患者的获益相关。
在铂 - 紫杉烷化疗中添加厄洛替尼耐受性良好，但并未诱导更高的MPR率或PFS，也未带来OS生存获益。接受厄洛替尼化疗并达到主要病理缓解的患者临床结局良好。
