Despite problems with vial labeling that weakened the findings of a recent phase II clinical trial, Peregrine Pharmaceuticals plans to move its new cancer drug bavituximab forward into a phase III trial. A second analysis of the phase II results, which adjusted for the labeling inconsistencies, still found that adding bavituximab to chemotherapy as a second-line treatment for non-small cell lung cancer (NSCLC) increased patients’ survival time, even though the difference may merely be due to chance. Bavituximab targets phosphatidylserine, a protein found on the surface of tumor blood vessels that suppresses the body’s immune response. By blocking phosphatidylserine, bavituximab allows the immune system to attack the cancer.
“The LKB1 (also called STK11) tumor suppressor is mutationally inactivated in ∼20% of non-small cell lung cancers (NSCLC). LKB1 is the major upstream kinase activating the energy-sensing kinase AMPK, making LKB1-deficient cells unable to appropriately sense metabolic stress. We tested the therapeutic potential of metabolic drugs in NSCLC and identified phenformin, a mitochondrial inhibitor and analog of the diabetes therapeutic metformin, as selectively inducing apoptosis in LKB1-deficient NSCLC cells. Therapeutic trials in Kras-dependent mouse models of NSCLC revealed that tumors with Kras and Lkb1 mutations, but not those with Kras and p53 mutations, showed selective response to phenformin as a single agent, resulting in prolonged survival. This study suggests phenformin as a cancer metabolism-based therapeutic to selectively target LKB1-deficient tumors.”
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.
About one-third of lung cancer patients treated with radiation therapy and chemotherapy experience recurrence at or near the original site. A study of patients with non-small cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) investigated the use of renewed radiation (reirradiation, or reRT) for such “locoregional recurrence.” ReRT relieved symptoms in 75% of NSCLC patients and conferred long-term survival in some, especially those who had little functional impairment at the time of treatment and had received higher doses of radiation. Some SCLC patients whose returning cancer was small and did not cause symptoms, and whose cancer had not spread outside the chest region, also experienced increased survival from reRT. For all other SCLC patients, reRT produced no meaningful benefits.
A recent study found stereotactic ablative radiotherapy (SABR) to be safe and effective for non-small cell lung cancer (NSCLC) treatment, offering better tumor control, lower toxicity, and greater convenience than conventional radiation therapy. The retrospective study focused on patients with NSCLC who could not be treated with surgery. Outcomes were especially beneficial for tumors that were smaller and had lower metabolism (measured by sugar absorption rate). SABR, also called stereotactic body radiation therapy (SBRT), uses higher doses of radiation over a smaller number of sessions compared to conventional radiation therapy.
A retrospective study assessed the use of weekly bevacizumab (Avastin) along with paclitaxel (Taxol) every 3 weeks in patients with advanced non-squamous, non-small cell lung cancer (NSCLC) who had previously received at least three rounds of treatment. The Avastin-Taxol combination was found to be an effective antitumor treatment. Some patients experienced serious side effects, including one death. However, overall toxicity was deemed acceptable compared to typical chemotherapy results in similar patients.
Most patients with advanced non-small cell lung cancer (NSCLC), who have mutations in the ALK gene, benefit significantly from treatment with the ALK inhibitor critozinib (Xalkori). The only currently FDA-approved test for these mutations, Abbott’s Vysis Break Apart FISH Probe Kit, may miss some patients with ALK mutations, but additional tests are under investigation. Further research is also exploring strategies to address the development of resistance to Xalkori. Several new ALK inhibitors are currently in development.
Testing for EGFR gene mutations in non-small cell lung cancer (NSCLC) helps identify patients who could benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs) like erlotinib (Tarceva), gefitinib (Iressa), or afatinib. However, there are no official recommendations for specific EGFR mutation tests. A study comparing three tests—cobas EGFR Mutation Test, Therascreen EGFR29 Mutation Kit, and 2× bidirectional Sanger sequencing—found that the cobas and Therascreen tests were more accurate and sensitive than Sanger sequencing. The cobas test required the smallest amount of tumor tissue, while the Sanger test can theoretically detect more types of mutations than the other tests.