Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer

The treatment of advanced non-small cell lung cancer remains an important area of research, with many questions about the use of chemotherapy still unanswered. It is now recognized that chemotherapy improves survival and alleviates disease-related symptoms in the population with advanced non-small cell lung cancer. However, it is unknown whether these benefits apply to patients with poor performance status (PS). These patients (Eastern Cooperative Oncology Group PS2) have inferior outcomes compared with more fit patients, and historically, they have been excluded from clinical trials. In other trials with broader eligibility, PS2 patients comprised fewer than 20% of the study populations. These factors have led to difficulty in ascertaining true outcomes in the PS2 patient population. However, the PS2 population accounts for a significant portion (up to 30% to 40%) of patients in oncology practice, and emerging data suggest that these patients may in fact garner benefits, such as prolonged survival and improved quality of life, from chemotherapy. Studies with single-agent vinorelbine or paclitaxel have shown improved survival with chemotherapy versus supportive care that remain significant when stratified by PS. A recent subset analysis of PS2 patients enrolled in a trial comparing carboplatin and paclitaxel with single-agent paclitaxel suggests that combination chemotherapy is a feasible option and is potentially preferable to single-agent therapy. Importantly, several analyses have shown that toxicity is not necessarily worse in this population compared with more fit patients. Because optimal agents or combinations have not been defined, novel strategies and therapeutics are urgently needed in this population.