medwireNews: Pemetrexed used in combination with erlotinib may have clinical advantage over single-agent pemetrexed when used as a second-line treatment in patients with non-squamous non-small-cell lung cancer (NSCLC), researchers report.
The findings arose from a multicentre, randomised, open-label, parallel phase II study conducted in 159 patients with NSCLC stage III or IV who had failed one prior platinum-based chemotherapy regimen.
The patients were randomly assigned to receive pemetrexed 500 mg/m2 every 3 weeks alone (n=83) or in combination with erlotinib 150 mg daily (n=76) until intolerable toxicity or disease progression. In addition, all patients received pretreatment with folic acid, vitamin B12 and dexamethasone.
Christian Dittrich (Ludwig Boltzmann Institute for Applied Cancer Research, Vienna, Austria) and colleagues found that patients receiving combination therapy had a significant 37% reduced risk for disease progression compared with those receiving monotherapy, with respective median progression-free survival times of 3.19 and 2.89 months.
Overall survival was also significantly prolonged in the pemetrexed plus erlotinib arm when compared with the pemetrexed arm (11.83 vs 7.75 months), as was time to treatment failure (3.00 vs 2.40 months).
However, the improved efficacy of the combined therapy was accompanied by an increase in the rate of serious adverse events (31.6 vs 12.0%) compared with monotherapy.
Drug-related grade 3/4 toxicity was also more frequently reported in the combined group, with haematological toxicities (anaemia, leukopaenia, neutropaenia and thrombocytopaenia) and rash/desquamation most commonly observed.
The researchers suggest that the difference in toxicity between the groups could be due to increased drug exposure to pemetrexed plus erlotinib; patients in this group received an average of 6.3 cycles of treatment compared with 4.3 cycles in the pemetrexed only group.
Of note, one patient treated with pemetrexed plus erlotinib died due to febrile neutropaenia that was considered drug related. Another patient in this group succumbed to a serious adverse event-related death due to lung abscess.
Writing in the European Journal of Cancer, Dittrich and co-authors recommend that a prospective randomised phase III trial, taking into account biological markers and other prognostic factors, should be carried out to define the patient group most likely to benefit from combination therapy.
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014
By Laura Cowen, medwireNews Reporter