Gefitinib, Erlotinib Increased Risk for Interstitial Lung Disease in Patients with Advanced NSCLC

“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.”

NICE to Bar Second-Line Use of Tarceva

“A proposal by (National Health Service) NHS cost regulators to no longer back the second-line use of Tarceva (erlotinib) to treat relapsed non-small cell lung cancer (NSCLC) has angered the drug’s manufacturer Roche and will no doubt come as a shock to patients.

“Following a review of existing guidance, the National Institute for Health and Care Excellence (NICE) has decided that treatment with Tarceva after first-line therapy has failed is no longer a cost-effective option for the NHS.

“According to Roche, the move means that more than 1,000 patients in England and Wales every year will be at risk from being left without an active second-line treatment option.”

Lung Cancer Drug Disappoints in 2 Late-Stage Trials

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.

Lung Cancer Drug BGB324 May Counteract Drug Resistance

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.

Rash from Tarceva May Herald Drug Effectiveness

Skin rash is a common side effect of the lung cancer drug erlotinib (Tarceva). However, a clinical trial suggests 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.

Effect of New Lung Cancer Drug Depends on MET Protein Expression Levels

The cell protein MET is overexpressed in more than half of non-small cell lung cancer (NSCLC) tumors. MET overexpression is associated with worse prognoses and plays a role in drug resistance to EGFR inhibitors like erlotinib (Tarceva). A recent clinical trial examined the effects of onartuzumab, which inhibits MET function, on recurrent NSCLC. Patients received either onartuzumab and Tarceva or Tarceva only. In patients who overexpressed MET, adding onartuzumab increased the time until cancer progression and prolonged overall survival. In contrast, in patients without MET overexpression, adding onartuzumab worsened outcomes. This finding highlights the importance of diagnostic testing in choosing the best cancer treatment. A clinical trial investigating the onartuzumab-Tarceva combination in MET-overexpressing patients only is currently enrolling participants.

Adding Tarceva to Avastin Maintenance Therapy Does Not Increase Lung Cancer Survival

Results from the ATLAS clinical trial indicate that adding erlotinib (Tarceva) to maintenance therapy with bevacizumab (Avastin) does not increase survival in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who had been successfully treated with chemotherapy and Avastin received continued treatment with Avastin plus either Tarceva or a placebo. In patients who received both Avastin and Tarceva, the cancer took longer to start progressing again than in the patients given only Avastin (4.8 vs 3.7 mo, on average), but overall survival was not significantly different. Moreover, patients treated with both Tarceva and Avastin experienced more side effects. However, the benefits of added Tarceva were greater in the subgroup of patients with mutations in the EGFR gene.

Personalized Treatment Yields Results for Cancer Patients

Personalized cancer medicine uses genetic testing of patients’ tumors to guide individually tailored treatment decisions. Such tests can determine which chemotherapies would likely be most effective and whether the patient may benefit from novel drugs targeting specific mutations. One example is the case of Elizabeth Lacasia, who has advanced bronchioalveolar carcinoma, a type of non-small cell lung cancer (NSCLC). Testing revealed that she does not have any of the mutations targeted by the new drugs. Based on her test results, she was treated with a combination of Tarceva (erlotinib) and Alimta (pemetrexed) following an alternating schedule that has been proven effective for people with her cancer type. Her cancer has been in remission for 2 years.

Molecular Marker Predicts Response to Iressa and Tarceva

A molecule named Mig 6 may help predict how much a patient will benefit from EGFR inhibitors like Tarceva (erlotinib) or Iressa (gefitinib). Preliminary results from an ongoing study reveal that cancer cells that are resistant to EGFR inhibitors have high Mig 6 levels. In an animal model of non-small cell lung cancer (NSCLC) without EGFR mutations, higher Mig 6 levels predicted more resistance to EGFR inhibitor treatment. Finally, NSCLC patients with low Mig 6 levels were more likely to survive for over a year after EGFR inhibitor treatments. Mig 6 may help identify patients who would most benefit from EGFR inhibitors.