“Updated data from the phase III AVAPERL trial hint that there might be an overall survival (OS) benefit of using bevacizumab in combination with pemetrexed as maintenance therapy in patients with advanced nonsmall cell lung cancer (NSCLC).
“ ‘The AVAPERL study was not powered to detect differences in OS between treatment arms’, Fabrice Barlesi, of Aix Marseille University in France, and colleagues observe in the Annals of Oncology.
“ ‘The analysis revealed, however, that OS was numerically increased by nearly 4 months in patients treated with maintenance bevacizumab-pemetrexed as compared with bevacizumab alone’, the international team of researchers reports.”
Editor’s Note: Maintenance therapy is “treatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy. It may include treatment with drugs, vaccines, or antibodies that kill cancer cells, and it may be given for a long time,” according to the National Cancer Institute. Patients in this study were found to have longer survival times when taking a combination of the drugs bevacizumab and pemetrexed as a maintenance therapy than when taking bevacizumab alone.
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 U.S Food and Drug Administration (FDA) has granted regular approval to the drug crizotinib (Xalkori) for the treatment of advanced non-small cell lung cancer (NSCLC) in patients who have mutations in the ALK gene. Xalkori received accelerated approval for this application in August 2011. Regular approval was awarded based on the results of a study examining patients with advanced NSCLC whose cancer had progressed despite first-line chemotherapy. Patients treated with Xalkori went an average of 7.7 months without further cancer worsening, compared to 3.0 months in those receiving the chemotherapy agents pemetrexed (Alimta) or docetaxel (Taxotere). Tumors shrank in 65% of the Xalkori-treated patients, compared to 20% with Alimta or Taxotere. However, overall survival did not differ between the Xalkori group and the chemotherapy group.
The recent PointBreak clinical trial compared two treatment regimens for non-squamous non-small cell lung cancer (NSCLC). Previously untreated patients with advanced non-squamous NSCLC received initial treatment with carboplatin (Paraplatin), bevacizumab (Avastin), and either pemetrexed (Alimta) or paclitaxel (Taxol/Abraxane). The Alimta-treated group was then given maintenance treatment with Alimta and Avastin, while the other patients received Avastin only. Alimta treatment was associated with slightly longer times until the cancer progressed again (average 6.0 months, compared to 5.6 in the Alimta-free regimen). However, overall survival did not differ between the groups. The two regimens differed in what specific side effect were most common, but had similar overall toxicities and were generally tolerable.
Patel JD, Socinski MA, Garon EB, Reynolds CH, et al. Journal of Clinical Oncology. Oct 21, 2013.
PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC).
Overall survival did not improve with the PemCBev regimen compared with the PacCBev regimen, although progression-free survival was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability.
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.
Maintenance therapy with bevacizumab (Avastin) and pemetrexed (Alimta) showed promising effects in the AVAPERL phase III clinical trial. Patients with advanced non-small cell lung cancer (NSCLC) were first treated with Avastin, Alimta, and cisplatin (Platinol). Those who responded to the treatment were either continued on both Avastin and Alimta or on Avastin only. Patients maintained on both drugs experienced more serious side effects, but went for longer without their cancer progressing (7.4 months on average, compared to 3.7 months for Avastin-only patients). While the study did not examine the benefits of Alimta-only maintenance treatment, the results suggest that the Avastin-Alimta combination is preferable to maintenance on Avastin only.
The Spruce trial, a phase II clinical trial examining the effectiveness of the cancer drug OGX-427 in non-small cell lung cancer (NSCLC), is now open for enrollment. The trial will study patients with previously untreated, advanced non-squamous NSCLC. They will receive the chemotherapy agents carboplatin (Paraplatin) and pemetrexed (Alimta) in combination with either OGX-427 or a placebo. The sponsors also plan to add the Cedar trial, which will investigate the use of OGX-427 in squamous cell NSCLC. OGX-427 inhibits Hsp27, a protein that is highly expressed in many tumor cells. The drug may be especially promising for patients without mutations that make them eligible for currently available targeted therapies.
The molecular diagnostics company Rosetta Genomics has received permission to patent their Rosetta Lung Cancer Test. The test analyzes lung tumor tissue and distinguishes squamous cell carcinoma (SCC) from other types of non-small cell lung cancer (NSCLC). Clearly identifying a patient’s cancer subtype is becoming increasingly important for choosing an optimal treatment plan, thanks to the increasing role of targeted therapies and the growing understanding of how drug effects can differ among various cancer subtypes. For example, pemetrexed (Alimta) and bevacizumab (Avastin) benefit many NSCLC patients, but are not recommended for those with SCC. The patent allowance will permit Rosetta to develop their test for use in patients.