MGluR received erlotinib as third line treatment. Almost all patients had previously received platinum based chemotherapy. As compared to BSC, treatment with erlotinib resulted in significantly prolonging OS and PFS. The QoL evaluation examined the time to clinically significant deterioration of three common lung cancer symptoms and showed that patients receiving erlotinib had a significantly longer median time to deterioration for all three symptoms. QoL response analyses showed that 44%, 34% and 42% of patients receiving erlotinib showed improvement of these three symptoms, respectively. There was a significantly greater improvement of physical function and global QoL. Subgroups with greater likelihood of response to erlotinib were widely catalogued, but multivariate P2X receptor analysis revealed that a non smoking history was the only significant independent predictive factor for survival benefit with erlotinib. The use of erlotinib as third line therapy is supported by the fact that 50% of patients in the BR.21 study had already received two lines of chemotherapy. Moreover, this EGFR inhibitor showed positive results for patients with a PS of 0 1 as well as for those with a PS of 2 3.
Median OS was 8.3, 4.3 and 1.9 months in the PS 0 1, PS 2 and PS 3 groups, respectively. It should be noted that the erlotinib toxicity profile was relatively mild, including JNK signaling pathway rash and diarrhea. After taking the above results into consideration, erlotinib received approval for patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. Owing to lack of direct comparison of erlotinib to chemotherapeutic agents used in second line treatment, use of erlotinib in the second line treatment is restricted to selected populations. Clinical predictive factors, such as never smoking status, female gender, Asian ethnicity, adenocarcinoma or bronchoalveolar carcinoma histology, as well as molecular predictive factors, such as EGFR and KRAS mutations, should be taken into account when choosing NSCLC secondline treatment. The role of erlotinib in third rivaroxaban line treatment seems to be completely different. The main objectives of treatment at this stage are the palliation of symptoms and QoL maintenance. As BR.21 study showed, erlotinib represents the best therapeutic option for heavily pre treated patients with deteriorated PS, when survival and QoL determinants are considered.
Cappuzzo et al. showed that erlotinib maintenance therapy is well tolerated and significantly prolongs PFS as compared to placebo. A recent phase II trial by Rossi et al. confirmed the activity and efficacy of erlotinib as second and third line treatment in pretreated elderly NSCLC patients, especially in terms of OS. The pharmacoeconomic review by Lyseng Williamson concludes that erlotinib as second or third line treatment is cost saving when compared to docetaxel or pemetrexed in this group of patients. Gefitinib. Gefitinib was approved by the Food and Drug Administration in May 2003 through an accelerated approval procedure for third line therapy based on two double blind, randomized phase II trials. The Iressa Dose Evaluation in Advanced Lung Cancer 1 study enrolled 210 patients in Europe, Australia, South Africa and Japan to receive 250 mg/day.