The results of the studies of maintenance pemetrexed therapy are encouraging; the observed survival benefit is clinically relevant and relatively large considering the poor survival in patients with advanced NSCLC. Furthermore, pemetrexed appears to be well tolerated. There are, however, several limitations to the studies that have been conducted:
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Few patients (< 20 %) on the control arms received pemetrexed at progression. Several studies suggest that pemetrexed is superior to other cytotoxic agents in non-SCC. Thus, it is possible that the survival benefit (or parts of it) is due to different efficacy of the administered drugs and not the maintenance therapy. In this study, pemetrexed will be the therapy of choice at progression.
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As in many clinical studies, elderly were underrepresented; few of the participants in these studies were older than 70 years. Median age at diagnosis of lung cancer is 71 years. Elderly have a higher frequency of comorbidity, which is a general concern when administering chemotherapy. Thus, there is a need to further investigate the efficacy and tolerability of maintenance therapy in elderly.
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Only patients in performance status (PS) level 0 and 1 were included. In general, PS is a strong prognostic factor in cancer patients. A large proportion, approximately one third, of patients has a poor PS due to their malignant disease. It is widely debated whether these patients should receive the same therapy as more fit patients. There is a need to explore whether PS 2 patients tolerate and benefit from maintenance therapy.
In general, clinical trials leading to introduction of new therapies usually enrol highly selected patients. There are concerns that maintenance therapy consumes time for patients with a limited prognosis; not all patients benefit from the therapy; some will experience serious side effects; and the financial cost should also be considered. Thus, there is a need to evaluate the effectiveness in a more general population of patients. In previous studies, we have enrolled a larger proportion of elderly (35 % were 70 years or older) and PS 2 patients (22-28 %) [7-9, 21].
The overall aim is to investigate whether immediate maintenance pemetrexed therapy prolongs survival compared to observation and pemetrexed therapy at progression in patients with advanced NSCLC. Furthermore, we will explore whether patients with PS 2 and elderly ≥ 70 years tolerate and benefit from maintenance therapy; and what clinical characteristics and blood biomarkers are associated with sensitivity and tolerability of such therapy.
