Lay Summary: Alimta and cisplatin are FDA approved for second and first line therapy of lung cancer. Carboplatin can be substituted for cisplatin.
National cancer Centers Network (NCCN), an alliance of nineteen of the world’s leading cancer centers, recently added pemetrexed (Alimta®, Eli Lilly and Company) as an option for second-line therapy for lung cancer. The panel indicated that it has been shown to be equivalent to docetaxel (Taxotere®, Sanofi-Aventis) in efficacy but with less toxicity. At this time, FDA approves, as follows: ALIMTA is indicated in combination with cisplatin therapy for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer. ALIMTA is not indicated for treatment of patients with squamous cell non-small cell lung cancer. ALIMTA is indicated as a single-agent for the treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer after prior chemotherapy.
It is FDA approved for mesothelioma in combination with cisplatin.
A prospective, randomized, multicenter Phase III study was conducted to compare ALIMTA plus carboplatin with the commonly used regimen of GEMZAR® (gemcitabine HC1 for injection) plus carboplatin (ASCO Abstract # 7517 ). The study, conducted by the Norwegian Lung Cancer Group, enrolled 446 chemonaïve patients with either stage IIIB or IV NSCLC. The primary purpose of the study was to evaluate if the ALIMTA-carboplatin combination provided increased quality-of-life benefits while offering comparable survival data. As such, the primary endpoint was quality of life (defined in the study as nausea/vomiting; dyspnea or a difficulty in breathing, and; fatigue) and the secondary endpoint was overall survival.
Thus far, 384 patients have been analyzed for toxicity and there were fewer patients in the ALIMTA arm who experienced Grade 3/4 thrombocytopenia or a low platelet level (48 vs. 107, p<.001); leukopenia or a lowering of leukocyte white blood cells (44 vs. 89, p<.001), and; granulocytopenia or a lowering of granulocyte white blood cells (78 vs. 98, p=.02). More patients in the GEMZAR arm received transfusion of platelets (5 vs. 19, p=.02). At this point, no difference in survival has been observed.
According to available guidelines, pemetrexed is indicated for persons who have histological or cytological confirmation of NSCLC with stage III or IV disease not amenable to curative therapy, and who have had prior chemotherapy for advanced disease. According to these guidelines, candidates for pemetrexed should have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and have adequate bone marrow, renal and hepatic function.
NCCN in NSCL-F, 1 says that carboplatin with Alimta has been proven effective.
Scagliotti G, et al Phase III Study of Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin in Chemonaive patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC). Proceedings from the International Association for the Study of Lung Cancer meeting. 2007. Abstract #PRS-03.
Gronberg B, et al. A Phase III Study by the Norwegian Lung Cancer Group: Pemetrexed + Carboplatin vs. Gemcitabine + Carboplatin as First-Line Chemotherapy in Stage IIIB/IV Non-Small Cell Lung Cancer. Proceedings from the International Association for the Study of Lung Cancer meeting. 2007. Abstract A3-04.
Alimta, Product Profile, 2013
Zinner RG, Fossella FV, Gladish GW, et al. Phase II study of pemetrexed in combination with carboplatin in the first-line treatment of ad-vanced nonsmall cell lung cancer. Cancer. 2005 Dec 1;104(11):2449-56.
Zukin M, Barrios CH, Pereira JR, et al: Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non–small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. June 17, 2013.