“Chemotherapy yielded improved PFS vs. treatment using epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non–small cell lung cancer with wild-type epidermal growth factor receptor.
“However, researchers noted that chemotherapy did not confer a benefit over EGFR TKIs in terms of OS.
“In the meta-analysis, researchers conducted a literature search of several scientific databases, including PubMed, Embase, Cochrane database, and abstracts from meetings of the American Society of Clinical Oncology and the European Society of Medical Oncology.”
Editor’s note: The study described here compared chemotherapy to treatment with targeted therapy drugs called EGFR TKIs for patients with non-small cell lung cancer (NSCLC) whose tumors did NOT have mutations in the EGFR gene. (EGFR mutations and other mutations are often tested to help determine patients’ treatment options.) The scientists found that chemotherapy may be a better option for these patients. Chemotherapy seemed to extend the time that patients lived without their disease worsening. However, it did not show any benefit over EGFR TKIs in terms of overall survival.
“Earlier today the US Food and Drug Administration granted accelerated approval to ceritinib (Zykadia) for the treatment of patients with metastatic ALK-positive non–small-cell lung cancer (NSCLC). About 2% to 7% percent of NSCLC patients have ALK-positive disease.
“The new drug, a tyrosine kinase inhibitor, was approved 4 months early under the FDA’s accelerated approval program and is intended for the treatment of patients who previously received the ALK-inhibitor crizotinib.”
Editor’s note: FDA approval means that doctors can now begin prescribing ceritinib to treat patients with advanced non-small cell lung cancer (NSCLC) whose tumors have mutations in the ALK gene, as detected by molecular testing. We previously posted about ceritinib here.
“Patients treated with advanced non–small cell lung cancer treated with gefitinib and erlotinib demonstrated a significant increased risk for all-grade and fatal interstitial lung disease events, according to results of a systematic review and meta-analysis.
“Erlotinib (Tarceva, Genentech) and gefitinib (Iressa, AstraZeneca), both of which are oral epidermal growth factor receptor tyrosine kinase inhibitors, are commonly used during treatment of advanced NSCLC. However, the overall risk for interstitial lung disease events are not known.”
Crizotinib (Xalkori) is effective for patients with non-small cell lung cancer (NSCLC) who have a mutation in the ALK gene, but their cancer usually develops resistance to the drug. However, this resistance may affect only part of the cancer, while the majority of the disease still responds to Xalkori. In such cases, localized radiation may be used to destroy the resistant part of the cancer (a technique dubbed ‘weeding the garden’) while patients continue to take Xalkori. In a small study, patients treated with this method could take Xalkori almost three times longer than those not eligible for the treatment. Longer times on Xalkori were associated with higher rates of 2-year survival. The average time without further relapse after the first radiation treatment was 5.5 months, and patients could be treated multiple times. Similar approaches may be effective with other targeted therapies.
In a recent phase III clinical trial, the cancer drug dacomitinib was no more effective than a placebo at prolonging survival for patients with advanced non-small cell lung cancer (NSCLC) for whom standard therapy had failed. Like the targeted drugs erlotinib (Tarceva) and gefitinib (Iressa), dacomitinib blocks the protein EGFR, but it also inhibits a number of similar, related proteins. Another trial compared dacomitinib to Tarceva in NSCLC patients who had previously received at least one EGFR inhibitor. Dacomitinib did not increase time without cancer worsening compared to Tarceva. Results from a third phase III trial, which compares dacomitinib to Iressa in NSCLC patients with EGFR mutations, are expected next year.
An ongoing clinical trial is evaluating the effects of cancer drug tivantinib in non-small cell lung cancer (NSCLC). The trial studies patients with advanced non-squamous NSCLC who do not have any mutations in the EGFR gene. Patients receive erlotinib (Tarceva) either by itself or in combination with tivantinib. Enrollment in the trial was stopped because rates of interstitial lung disease (ILD), which can cause lung scarring, may be higher in patients receiving tivantinib. (No such increased levels of ILD were seen in a different trial using tivantinib.) For the patients already enrolled, overall survival, time without cancer worsening, and percentage of patients experiencing tumor shrinkage all seem increased in tivantinib-treated patients. However, it is not yet clear whether these effects are indeed caused by tivantinib or are due to chance.
The ALK inhibitor crizotinib (Xalkori) has shown effectiveness in patients with non-small cell lung cancer (NSCLC) who have changes in the ALK gene that make the gene overactive (so-called ‘ALK-positive’ patients). A recent clinical trial compared Xalkori to chemotherapy as a second-line treatment in these patients. Over 300 patients with ALK-positive advanced NSCLC who had undergone one previous round of chemotherapy were treated either with Xalkori or one of the chemotherapy drugs pemetrexed (Alimta) or docetaxel (Taxotere). Tumors shrank in 65% of Xalkori-treated patients, compared to 20% of those receiving chemotherapy. The Xalkori-treated patients also went longer without their cancer worsening, experienced fewer symptoms, and reported higher quality of life.
The protein Axl has been associated with cell transformation processes that contribute to the spread of cancer through the body and to cancers becoming drug resistant. A recent study investigated the effect of the Axl inhibitor BGB324 on non-small cell lung cancer (NSCLC) cells that had become resistant to EGFR inhibitors like erlotinib (Tarceva). BGB324 restored the effectiveness of EGFR inhibitors against these cancer cells, which had been grown either in a matrix or as tumors in mice. BGB324 also appeared to enhance the effectiveness of the chemotherapy drug docetaxel (Taxotere) and of bevacizumab (Avastin). BGB324 may therefore be a promising new candidate for treating drug-resistant NSCLC. The drug will be tested in a phase Ib clinical trial for NSCLC in 2014.
Skin rash is a common side effect of the lung cancer drug erlotinib (Tarceva). However, a clinical trialsuggests that this rash can be a good sign and can be used to guide dosing. One hundred twenty-four patients with advanced non-small cell lung cancer (NSCLC) received first-line treatment with Tarceva. The drug dose was gradually increased until patients developed a skin rash or other side effects that prevented further dose increases. Seventy percent of patients developed a skin rash. Patients who developed a skin rash survived longer than those who did not (6.8 months longer on average), even though they did not differ in how much the treatment reduced the growth of their tumors.