Maintenance Therapy with Alimta Improves Outcomes in Lung Cancer

Patients whose advanced nonsquamous, non-small cell lung cancer (NSCLC) responds to chemotherapy with pemetrexed (Alimta) and cisplatin (Platinol) appear to benefit from continuing Alimta treatment after they have achieved remission (continuation maintenance therapy). Results from the PARAMOUNT clinical trial showed that maintenance treatment with Alimta prolonged time without cancer worsening and increased survival times compared to treatment with a placebo. Continuation maintenance therapy with Alimta may be the preferable treatment choice for patients who do not experience significant toxicity from Alimta.


Afatinib May Be Candidate for First-Line Treatment in Certain Lung Cancers

Results from the LUX-Lung 3 clinical trial show that afatinib appears to be well tolerated and more effective than chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who have a mutation in the EGFR gene. Afatinib produced higher response rates and longer periods without cancer progression than cisplatin (Platinol) plus pemetrexed (Alimta), suggesting that it could be considered as a first-line therapy in advanced EGFR-mutant NSCLC. Afatinib, which is under priority review for approval by the FDA, may be effective in patients resistant to other EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa). However, no trials so far have directly compared afatinib with Tarceva or Iressa.


PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for NSCLC

In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data.

Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.


Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous NSCLC

AVAPERL evaluated the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment. 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.


Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations

The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation–positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS). 

In this phase III study, it was found that afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.


Adding Paraplatin to Alimta Increases Survival in Lung Cancer Study

Results from a phase III clinical trial suggest that adding carboplatin (Paraplatin) to pemetrexed (Alimta) can improve outcomes in non-small cell lung cancer (NSCLC). Over 200 patients with advanced NSCLC received first-line treatment with Alimta either by itself or in combination with Paraplatin. The combination of the two chemotherapy agents extended the time before the cancer started growing again, and prolonged survival compared to Alimta alone. However, the combination treatment group had a higher incidence of serious side effects and four treatment-associated deaths.


Comparison of Combination Chemotherapy Regimens Shows No Significant Differences

Both pemetrexed (Alimta) plus carboplatin (Paraplatin) and Paraplatin plus paclitaxel (Taxol/Abraxane) plus bevacizumab (Avastin) are effective chemotherapy regimens against non-small cell lung cancer (NSCLC). However, until recently, the safety and efficacy of the two regimens had not been directly compared. To evaluate whether one regimen was superior, a phase III clinical trial determined how long patients with advanced non-squamous NSCLC remained free of either cancer progression or severe toxic side effects when treated with either of the two regimens. While patients receiving the Alimta plus Paraplatin regimen tended to have slightly longer relapse- and toxicity-free periods than those given Paraplatin plus Taxol/Abraxane plus Avastin, the difference was not very pronounced and could have happened by chance. The two regimens also did not differ regarding overall time until cancer progression, response rate and overall survival time.


New Clinical Trial of Drug OGX-427 Aims to Help Patients Ineligible for Targeted Therapies

OncoGenex Pharmaceuticals announced that it will begin the Spruce clinical trial, a phase II study investigating the use of their cancer drug OGX-427 in non-small cell lung cancer (NSCLC). Patients with advanced non-squamous NSCLC will receive first-line treatment with chemotherapy using carboplatin (Paraplatin) and pemetrexed (Alimta), either with or without the addition of OGX-427. OGX-427 inhibits a protein called Hsp27, which is elevated in many cancers. The study investigators suggest that OGX-427 may be especially helpful for patients whose cancers lack certain mutations that would make them eligible for currently available targeted therapies.


Impact of renal function on treatment options and outcomes in advanced non-small cell lung cancer

Certain chemotherapeutic agents commonly used for advanced non-small cell lung cancer (NSCLC) require minimum threshold renal function for administration. To determine how such requirements affect treatment options, we evaluated renal function patterns in this population. We performed a single-center retrospective analysis of patients treated for stage IV NSCLC from 2000 to 2007. Associations between patient characteristics, calculated creatinine clearance (CrCl), and clinical outcomes were determined.

In this cohort of patients treated for stage IV NSCLC, renal function falls below commonly used thresholds for cisplatin and for pemetrexed in fewer than a quarter of patients. However, these declines may preclude administration of these drugs for prolonged periods.