Chemotherapy Outcomes by Histologic Subtypes of Non–Small-Cell Lung Cancer: Analysis of the Southwest Oncology Group Database for Antimicrotubule-Platinum Therapy

Abstract

Histological subtyping has been advocated to select chemotherapy for patients with advanced stage non-small-cell lung cancer (NSCLC). Data from four randomized trials (S9308, S9509, S9806 and S0003) administering an antimicrotubular agent (a taxane or vinorelbine) plus platinum in patients receiving first line treatment for advanced stage NSCLC were analyzed. Of 1146 patients included in this analysis there was no difference in OS or PFS by histological subtype. Since the great majority of advanced NSCLC patients continue to receive chemotherapy, defining molecular-based predictive markers of responsiveness is warranted. Objectives Histologic subtyping has been advocated to select chemotherapy for patients with advanced-stage non-small-cell lung cancer (NSCLC). To determine if histologic subtype was associated with efficacy for the commonly used antimicrotubular (AMT) agents, paclitaxel, docetaxel and vinorelbine plus a platinum compound, we examined the Southwest Oncology Group (SWOG) lung cancer database. Methods Data from 4 randomized trials (S9308, S9509, S9806 and S0003) administering an AMT agent plus platinum in patients receiving first-line treatment for advanced stage NSCLC were analyzed. Overall survival (OS) and progression-free survival (PFS) comparisons were performed using Cox proportional hazard regression, adjusting for sex. Median survival times were estimated by Kaplan-Meier. Results Of 1146 patients included in this analysis, 640 had adenocarcinoma (56%), 220 had squamous cell carcinoma (19%), 121 had large cell carcinoma (11%) and 165 had NSCLC not otherwise specified (NOS)(14%). Median OS times by histologic subtypes were 8.5, 8.4, 8.2, and 9.6 months, respectively, and median PFS times were 4.2, 4.3, 4.3, and 4.6 months, respectively. No difference in OS or PFS was observed by histologic subtype and, specifically, between nonsquamous and squamous histologies. Conclusions This pooled analysis from 4 SWOG trials employing an AMT-platinum regimen did not show a difference in survival outcomes by histologic subtype. Because the majority of patients with advanced NSCLC continue to receive chemotherapy, defining molecular-based predictive markers of responsiveness is warranted.

Current and Emergent Therapy Options for Advanced Squamous Cell Lung Cancer

“…[60][61][62] The guidelines do not specify preferences for individual platinum-based doublet chemotherapy regimens approved for advanced SqCLC [21][22][23] because their efficacy is comparable, resulting in a median OS of approximately 8 to 11 months. 26,[63][64][65][66][67][68] An individual patient data metaanalysis suggested similar efficacy for cisplatin-versus carboplatin-based third-generation doublet regimens in SqCLC. 69 However, the preferred clinical practice in the United States is for carboplatin-based chemotherapy combinations.…”

“…Although the less than 30% of patients eligible for pembrolizumab treatment may experience improved outcomes, current guideline recommendations for most treatment-naive patients, even those with PS 0 to 1, remain much the same as a decade ago, with median survival of approximately 8 to 11 months for patients receiving first-line platinum-doublet chemotherapy. 26,[63][64][65][66][67][68] The choice of treatment for patients with PS 2 or who are elderly is markedly dependent not only on efficacy but also on the presence of comorbidities and toxicity profile; however, systemic therapy is recommended. [21][22][23] Given the large proportion of patients with advanced SqCLC who have these characteristics, they may have a considerable impact on the treatments patients receive.…”

S‐1 plus cisplatin as first‐line treatment of patients with advanced non‐small cell lung cancer in Taiwan

“…In this study, no difference was observed in terms of efficacy according to histology. To date, no other chemotherapy has shown differences in survival outcomes by histologic subtype, except pemetrexed 12,13. When comparing SP to other first-line chemotherapy in advanced NSCLC, PFS of 5.6 months reported in this study was also comparable to that of previous phase 2 studies that used cisplatin combined with vinorelbine or docetaxel conducted in Taiwan, with median PFS of 5.6 months or time to disease progression of 4.7 and 6.8 months, respectively [14][15][16].…”

Novel agents in development for advanced non-small cell lung cancer

“…Under the current staging system, AJCC TNM 7th edition, patients with malignant pleural or pericardial effusions are considered metastatic lesions (M1a) and patients with these conditions are considered as stage IV disease [Goldstraw et al 2007]. In first-line cooperative group trials in the United States, the most common histology was adenocarcinoma (approximately 45-55% of the cases), followed by squamous histology (approximately 20-30% of the cases) and large cell histology (approximately 10-15% of cases) [Wakelee et al 2006;Kelly et al 2013]. Squamous histology is closely associated with tobacco use and the prevalence of squamous histology may vary depending on the prevalence of tobacco use [Kenfield et al 2008].…”