Differences in Outcome and Toxicity Between Asian and Caucasian Patients With Lung Cancer Treated With Systemic Therapy

Ross A Soo; Tomoya Kawaguchi; Marie Loh; Sai-Hong I Ou; Marie P Shieh; Byoung-Chul Cho; Tony S Mok; Richie Soong


Future Oncol. 2012;8(4):451-462. 

In This Article

Abstract and Introduction


It is increasingly recognized that differences in overall survival and toxicity exist between Asian and caucasian patients with small-cell and non-small-cell lung cancer, with a longer survival, higher response rates and greater toxicity to chemotherapy and targeted therapy reported in Asian patients. Two global studies are used to illustrate how the proportions of Asian patients can influence survival outcome. Ethnicity is an important and complex characteristic that should considered in the design and conduct of a global clinical study, as the safety, tolerability and response may vary between Asian and caucasian patients. Whether ethnic differences in lung cancer survival are attributed to genetic differences among races or are simply a surrogate marker of differences in access to healthcare because of socioeconomic differences is unclear. Carefully designed prospective studies investigating ethnic-specific determinants of sensitivity and toxicity to systemic therapy are warranted.


Lung cancer is one of the most common malignancies in the world, accounting for 1.6 million cases annually, or 12% of all newly diagnosed cancers, and is also the leading cause of cancer deaths worldwide, causing 1.4 million deaths annually.[1] In many western countries, lung cancer rates have declined, but, by contrast, the incidence of lung cancer is predicted to increase substantially in Asia, especially among males.[2,3] Approximately 80% of cases are non-small-cell lung cancer (NSCLC), and these patients are usually diagnosed in the advanced stage where systemic therapy is the usual treatment for suitable patients. As new drug development is time consuming and costly, the conventional approach is to conduct global clinical studies, enabling appropriate sample sizes to be reached in a relatively short time frame, thus eliminating the need for redundant clinical trials with similar objectives conducted in different countries.

It is known that tumor histology plays an important role in the overall survival of patients with lung cancer. Cetin and colleagues recently confirmed this notion using data from the Surveillance, Epidemiology and End Results (SEER) Program, stratifying 51,749 stage IV NSCLC patients by major histologic subtype.[4] Survival was highest in patients with bronchioloalveolar adenocarcinoma and lowest in patients with large-cell tumors, with a 1-year survival of 29.1 and 12.8%, respectively. Ou et al. reported that adenocarcinoma constituted a greater proportion of histology type among native-born patients in three southern Californian counties, and bronchioloalveolar adenocarcinoma had the most significant and longest survival.[5]

Cetin and colleagues also demonstrated that female gender was independently associated with a decreased risk of death.[4] This reflects similar findings by other studies that reported that gender is associated with treatment response and overall survival.[6–8] One particular study reviewed 18,967 elderly patients with early-stage NSCLC between 1991 and 1999 from the SEER Registry linked to Medicare records and found that women in all treatment groups had statistically significant better survival compared with males. The survival advantage of women was specific to adenocarcinoma and large-cell carcinoma cases. No gender differences in overall survival among patients with squamous cell carcinomas were found.[9]

Asian ethnicity was also associated with a decreased risk of death in a study by Cetin et al..[4] Previously, the role of ethnicity in lung cancer has been focused on lung cancer epidemiology and risks. However, it is increasingly being recognized that differences in overall survival and toxicity exist between Asian and caucasian patients with lung cancer. As such, bridging studies are often conducted in Asian countries, especially in Japan, to establish the dosage in their ethnic group.[10] As more lung cancer studies are being conducted worldwide, especially in Asia, potential ethnic differences may influence outcomes.

In this paper, we will review the differences in survival, response rates and toxicity between Asian and caucasian studies of NSCLC and small-cell lung cancer (SCLC) treated with systemic chemotherapy and targeted therapy, and discuss the impact of these differences on study design. A review of the underlying biological and genetic factors accounting for interethnic differences in outcome is beyond the scope of this article and has been discussed elsewhere.[11–13] Likewise, ethnic differences in lung cancer epidemiology have been reviewed in other publications.[14–16]