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.


Alimta-Paraplatin Combination Appears to Be Effective Treatment for Elderly Lung Cancer Patients

Most elderly patients with advanced non-small cell lung cancer (NSCLC) do not receive chemotherapy and no age-specific guidelines for choosing chemotherapy agents exist. A phase II clinical trial investigated treatment with pemetrexed (Alimta) and carboplatin (Paraplatin) for elderly (age 70+ years) patients with advanced NSCLC and little functional impairment. The combination treatment was as effective in these patients as it had been in younger populations in previous studies and it was more effective than either pemetrexed or carboplatin alone. While some patients experienced serious side effects, especially blood-related complications, overall toxicity was acceptable, suggesting that combined Alimta and Paraplatin may be a viable treatment option for similar patients.


Pemetrexed and carboplatin, an active option in first-line treatment of elderly patients with advanced non-small cell lung cancer (NSCLC): A phase II trial

The combination pemetrexedcarboplatin could be a valuable treatment option in elderly patients, as indicated by this phase II trial. Neutropenia was the most common toxicity. The objective tumor response rate is within the range of data reported for pemetrexedcarboplatin in the general NSCLC population.


Avastin-Containing Chemotherapy May Be Safe in Lung Cancer Patients with Brain Metastases

Bevacizumab (Avastin), which is approved for treatment of a number of advanced-stage cancer types, is commonly avoided in patients with brain metastases (cancer that has spread to the brain) because of fear of brain hemorrhages (bleeding in the brain). A retrospective study of 52 patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy containing Avastin found no cases of serious bleeding events and no significant differences in survival or treatment side effects between patients with or without brain metastases. Avastin may therefore be a safe treatment option in NSCLC with brain metastases.

Research paper: https://www.jstage.jst.go.jp/article/acrt/20/2/20_47/_pdf


Overexpression of IGF1R and EGFR Genes May Worsen Lung Cancer Prognosis

The roles of the genes IGF1R and EGFR in lung cancer were examined in patients with non-small cell lung cancer (NSCLC) who had their primary tumor surgically removed. Patients whose tumors had increased expression of both IGFR1R and EGFR were more likely to experience recurrence of the cancer after a shorter amount of time and had shorter survival times after surgery. This finding suggests that concurrent overexpression of IGF1R and EGFR is a negative prognosis factor in NSCLC and may indicate patients who are more likely to benefit from novel treatments with IGF1R inhibitors.

Research paper: http://link.springer.com/article/10.1007/s00280-012-2056-y/fulltext.html