Pemetrexed Arm Research Articles

A Comparative Study Between Pemetrexed and Taxanes as First Line Treatment of Metastatic Lung Adenocarcinoma

Background: Adenocarcinoma of the lung is the most common type of lung cancer. Platinum agents in combination with other chemotherapy are currently the cornerstone for chemotherapy of advanced cases with metastasis. Objective: To compare the response rate of pemetrexed doublets versus taxanes doublets in patients with metastatic lung adenocarcinoma. Patients and Methods: This a prospective study that included 60 patients with pulmonary adenocarcinoma. Those patients received a platinum based doublet chemotherapy with additional treatment protocol; combined with either pemetrexed or taxanes (paclitaxel or docetaxel) with 30 patients in each arm. Tumor size, response rate and side effects of chemotherapy were evaluated in both arms. Results: The median reduction in tumor size in pemetrexed and taxan arms were 4.72 cm2 and 6.53 cm2 respectively. Nausea, fatigue, constipation and anorexia were more common in pemetrexed arm, while leukopenia, arthralgia and peripheral neuropathy were more common in taxan arm. Conclusion: Serious side effects such as leukopenia, and peripheral neuropathy were more common in taxan than pemetrexed arm. Pemetrexed is preferable to use as a fist line treatment for patients with metastatic adenocarcinoma of the lung. Keywords: Adenocarcinoma, Pemetrexed, Taxanes, metastatic lung cancer.

A Comparative Study Between Pemetrexed and Taxanes as First Line Treatment of Metastatic Lung Adenocarcinoma

Background: Adenocarcinoma of the lung is the most common type of lung cancer. Platinum agents in combination with other chemotherapy are currently the cornerstone for chemotherapy of advanced cases with metastasis. Objective: To compare the response rate of pemetrexed doublets versus taxanes doublets in patients with metastatic lung adenocarcinoma. Patients and Methods: This a prospective study that included 60 patients with pulmonary adenocarcinoma. Those patients received a platinum based doublet chemotherapy with additional treatment protocol; combined with either pemetrexed or taxanes (paclitaxel or docetaxel) with 30 patients in each arm. Tumor size, response rate and side effects of chemotherapy were evaluated in both arms. Results: The median reduction in tumor size in pemetrexed and taxan arms were 4.72 cm2 and 6.53 cm2 respectively. Nausea, fatigue, constipation and anorexia were more common in pemetrexed arm, while leukopenia, arthralgia and peripheral neuropathy were more common in taxan arm. Conclusion: Serious side effects such as leukopenia, and peripheral neuropathy were more common in taxan than pemetrexed arm. Pemetrexed is preferable to use as a fist line treatment for patients with metastatic adenocarcinoma of the lung.

Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non–Small-Cell Lung Cancer: AVAPERL (MO22089)

Maintenance therapy is associated with improved survival in patients with non-small-cell lung cancer (NSCLC), but few studies have compared active agents in this setting. AVAPERL evaluated the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment. Patients with advanced nonsquamous NSCLC received first-line bevacizumab 7.5 mg/kg, cisplatin 75 mg/m(2), and pemetrexed 500 mg/m(2) once every 3 weeks for four cycles. Those achieving response or stable disease were randomly assigned at a ratio of 1:1 to maintenance bevacizumab 7.5 mg/kg or bevacizumab 7.5 mg/kg plus pemetrexed 500 mg/m(2) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) after random assignment. In total, 376 patients received induction treatment, 71.9% achieved disease control, and 67.3% were randomly assigned to maintenance therapy, with 125 and 128 receiving single-agent bevacizumab and bevacizumab plus pemetrexed treatment, respectively. At a median follow-up of 8.1 months, PFS from random assignment was significantly improved in the bevacizumab plus pemetrexed arm (median, 3.7 v 7.4 months; hazard ratio, 0.48; 95% CI, 0.35 to 0.66; P < .001) per a stratified model. The PFS benefit extended across age, performance status, smoking history, and induction response (stable disease v partial response) subgroups. Any grade, grade ≥ 3, and serious adverse events occurred more often with bevacizumab plus pemetrexed maintenance. No new safety signals were observed. In an unselected population of patients with nonsquamous NSCLC who had achieved disease control with platinum-based chemotherapy plus bevacizumab, bevacizumab plus pemetrexed maintenance was associated with a significant PFS benefit compared with bevacizumab alone. The combination was well tolerated.

IS7-15 - A Large Retrospective Analysis of the Activity of Pemetrexed (PEM) in Patients (Patients) with ALK+ NSCLC Before Crizotinib (CRIZ)

ABSTRACT Background Retrospective small cohort studies suggest ALK+ NSCLC may be particularly sensitive to PEM. Methods PROFILE 1005 (NCT00932451; Pfizer) is a large phase 2 multi-center, single-arm study of CRIZ in previously treated ALK+ NSCLC. Eligibility criteria included patients with progressive disease from the PEM arm of companion trial PROFILE 1007. We retrospectively assessed objective response rate (ORR) and time to progression (TTP; first dose to objective progression) in patients who received PEM before CRIZ. ORR with CRIZ post-PEM was assessed. Results Of the 439 ALK+ patients enrolled as of June 2011, 369 (84.1%) received prior PEM (single agent or combination; any line advanced/metastatic) with a cumulative ORR of 18.7%. In patients who received PEM combinations first-line (1L; n = 120) or second-line (2L; n = 60), ORR was 24.2% and 16.7%; and median TTP was 6.9 months (mo; 95% CI: 6.0–7.4) and 6.9 mo (95% CI: 4.8–8.8), respectively. In patients who received 2L single-agent PEM (n = 80), ORR was 12.5% and median TTP was 5.3 mo (95% CI: 3.0–6.6). In patients treated with PEM third-line (3L) or later (n = 138), ORR was 16.7%. By line of PEM treatment, ORR was lower and TTP shorter than that reported in small ALK+ cohorts evaluating multiple lines of treatment. In 2L, previously reported ORR and median PFS with single-agent PEM in adenocarcinoma NSCLC were 12.8% (n = 158) and 3.5 mo (n = 283), and comparable to our findings. Patients who received 2L single-agent PEM (n = 80) subsequently achieved higher ORR with CRIZ (54%; 95% CI: 42–65). Similar analyses in the 1L and 3L groups are ongoing. Conclusions This retrospective study in predominantly never smokers with ALK+ NSCLC reports lower ORR and shorter TTP with PEM than that reported in smaller retrospective ALK+ NSCLC cohorts. This finding may be in part due to the inclusion of crossover patients from PROFILE 1007. This analysis and previous reports observed a tendency to a higher response rate and better PFS or TTP with PEM than in unselected populations in 2L, which may not be specifically related to the ALK status but to a higher sensitivity to cytotoxic agents in never smokers. Results from an ongoing phase 3 trial (PROFILE 1007) will provide additional information.

Pemetrexed versus docetaxel in second line non-small-cell lung cancer: Results and subsets analyses of a multi-center, randomized, exploratory trial in Chinese patients

BackgroundPemetrexed and docetaxel are established therapies in second line non-small cell lung cancer (NSCLC). Comparative data, concerning the two agents in the designated settings, however, are lacking in Chinese patients who account for the largest lung cancer population in the world. Methods and patientsWe designed and performed a multi-center, randomized, exploratory clinical trial of pemetrexed compared with docetaxel in second line chemotherapy in Chinese NSCLC patients. Eligible patients with histological or cytological diagnosis of stage IIIB or IV NSCLC, who were not suitable for curative therapy and had failed from prior first line chemotherapy regimen for at least 4 weeks, were randomized to receive either pemetrexed 500 mg/m2 intravenously day 1 with vitamin B12, folic acid, and dexamethasone, or docetaxel 75 mg/m2 intravenously day 1 with dexamethasone. Both regimens were implemented once every 21 days for 2 cycles. This study was designed to be a non-inferiority trial that compared tumor response for overall response rate (ORR) between the two drugs as primary endpoint. The secondary endpoints included disease control rate (DCR), Karnofsky performance status (KPS) scores and toxicities. Results260 patients were enrolled and randomly assigned to receive chemotherapy of either pemetrexed (132 patients) or docetaxel (128 patients). 106 patients in pemetrexed arm and 102 patients in docetaxel arm were evaluable for efficacy. The efficacy of pemetrexed was equivalent to that of docetaxel in the second-line treatment for Chinese NSCLC (ORR: pemetrexed vs. docetaxel = 9.4% vs. 4.9, p = 0.285, DCR: pemetrexed vs. docetaxel = 67.2% vs. 69.6%, p = 0.685). And pemetrexed seemed to slightly promote patients' average KPS score when comparing with docetaxel, although the difference was without statistical significance (changes of average KPS scores: pemetrexed vs. docetaxel = 0.28 ± 5.93 vs. -1.67 ± 8.57, p = 0.149). Patients receiving pemetrexed experienced significantly lower incidences of grade 3/4 neutropenia (7.0% vs. 27.6%, p < 0.001) and leucocytopenia (4.7% vs. 22.8%, p < 0.001) than those who received docetaxel. Also, there were lower incidences of alopecia, stomatitis, and neural abnormality for patients receiving pemetrexed than those receiving docetaxel. Incidence of serum glutamic oxaloacetic transaminase elevation, however, was higher in pemetrexed arm than in docetaxel arm (32.3% vs. 14.9%, p = 0.013). In addition, age ≥ 60 patients benefit from pemetrexed with equivalent efficacies yet much lower toxicities compared to docetaxel (DCR: pemetrexed vs. docetaxel = 66.67% vs. 81.58%, p = 0.146; grade 3/4 hematologic toxicities: pemetrexed vs. docetaxel = 17.25% vs. 39.6%, p = 0.016). ConclusionTreatment with pemetrexed resulted in equivalent efficacy outcomes and better safety profiles compared with docetaxel in second-line therapy for advanced NSCLC in Chinese lung cancer population. And age ≥ 60 patients may benefit from second-line single pemetrexed.

A large retrospective analysis of the activity of pemetrexed (PEM) in patients (pts) with ALK-positive (ALK+) non-small cell lung cancer (NSCLC) prior to crizotinib (CRIZ).

7599 Background: Retrospective small cohort studies suggest ALK+ NSCLC may be particularly sensitive to PEM. Methods: PROFILE 1005 (NCT00932451; Pfizer) is a large phase 2 multi-center, single-arm study of CRIZ in previously treated ALK+ NSCLC. Eligibility criteria included pts with progressive disease from the PEM arm of companion trial PROFILE 1007. We retrospectively assessed objective response rate (ORR) and time to progression (TTP; 1st dose to objective progression) in pts who received PEM prior to CRIZ. ORR with CRIZ post-PEM was assessed. Results: Of the 439 ALK+ pts enrolled as of June 2011, 369 (84.1%) received prior PEM (single agent or combination; any line advanced/metastatic) with a cumulative ORR of 18.7%. In pts who received PEM combinations 1st-line (1L; n=120) or 2nd-line (2L; n=60), ORR was 24.2% and 16.7%; and median TTP was 6.9 months (mo; 95% CI: 6.0–7.4) and 6.9 mo (95% CI: 4.8–8.8), respectively. In pts who received 2L single-agent PEM (n=80), ORR was 12.5% and median TTP was 5.3 mo (95% CI: 3.0–6.6). In pts treated with PEM 3rd-line (3L) or later (n=138), ORR was 16.7%. By line of PEM treatment, ORR was lower and TTP shorter than that reported in small ALK+ cohorts evaluating multiple lines of treatment. In 2L, previously reported ORR and median PFS with single-agent PEM in adenocarcinoma NSCLC were 12.8% (n=158) and 3.5 mo (n=283), and comparable to our findings. Pts who received 2L single-agent PEM (n=80) subsequently achieved higher ORR with CRIZ (54%; 95% CI: 42–65). Similar analyses in the 1L and 3L groups are ongoing. Conclusions: This retrospective study in predominantly never-smokers with ALK+ NSCLC reports lower ORR and shorter TTP with PEM than that reported in smaller retrospective ALK+ NSCLC cohorts. This finding may be in part due to the inclusion of crossover pts from PROFILE 1007. This analysis and previous reports observed a tendency to a higher response rate and better PFS or TTP with PEM than in unselected populations in 2L, which may not be specifically related to ALK status but to a higher sensitivity to cytotoxic agents in never-smokers. Results from an ongoing phase 3 trial (PROFILE 1007) will provide additional information.

Efficacy and safety of AZD6244 (ARRY-142886) as second/third-line treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)

8029 Background: The Raf/MEK/ERK signaling pathway is necessary for oncogenic function, and in NSCLC pts constitutive activation of this pathway has been correlated with BRAF/KRAS gene mutations. MEK1/2 inhibition block the Raf/MEK/ERK pathway since these kinases lie downstream of Ras, and ERK1/2 are the only known substrates of MEK1/2. Here we evaluate the efficacy and safety of oral AZD6244 - a potent, selective, ATP uncompetitive inhibitor of MEK1/2 - vs pemetrexed (PEM), which is currently approved and widely used for second/third-line treatment, in pts with advanced NSCLC. Methods: Pts who have previously received one or two chemotherapy regimens (prior surgery and/or localized radiation allowed) were randomized 1:1 to oral AZD6244 (100 mg BID) or iv infusion of PEM (500 mg/m2 over 10 min q3w). Pts in the PEM arm also received corticosteroid premedication and vitamin supplementation. The primary objective of this Phase II exploratory study was to evaluate the efficacy of AZD6244 vs PEM as second- or ...