“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 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.
A combination of the drugs carboplatin (Paraplatin), paclitaxel (Taxol/Abraxane), cetuximab (Erbitux), and bevacizumab (Avastin) has demonstrated effectiveness against non-small cell lung cancer (NSCLC) in a phase II clinical trial. One hundred two patients with advanced non-squamous NSCLC received the four-drug combo as a first-line treatment. Tumors shrank in 56% of patients and stopped growing in an additional 21%. Patients went an average of 7 months without their cancer progressing; the average survival time was 15 months. Four treatment-related deaths occurred, including two due to hemorrhage (heavy bleeding), which can be a rare but serious effect of Avastin treatment. This side effect profile was within the predefined safety margin. A phase III trial further investigating this drug combination for NSCLC is currently enrolling participants.
Combining cetuximab (Erbitux), bevacizumab (Avastin), and traditional chemotherapy in patients with non-small cell lung cancer (NSCLC) appeared to be safe and effective in a phase II clinical trial. Patients with advanced non-squamous NSCLC received Erbitux and Avastin in addition to carboplatin (Paraplatin) and paclitaxel (Taxol/Abraxane) as first-line treatment, followed by maintenance treatment with Erbitux and Avastin. Tumors shrank in 56% of patients and stopped growing in an additional 21%. Serious side effects were relatively rare; the rate was comparable to that of either Erbitux or Avastin alone. Both Erbitux and Avastin have shown efficacy in NSCLC by themselves, but may be more effective when given together. An ongoing phase III clinical trial will further investigate this drug combination.
Kim ES, Moon J, Herbst RS, Redman MW, Dakhil SR, et al. Journal of Thoracic Oncology. Nov 1, 2013.
Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC.
This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.
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.
The nanopharmaceutical CRLX101, a novel inhibitor of topoisomerase-1 and hypoxia-inducible factor (HIF)-1 alpha, may be capable of overcoming resistance of tumors to antiangiogenic agents, according to preclinical and early clinical studies that have evaluated CRLX101 in combination with bevacizumab (Avastin) and other antiangiogenic agents.
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.
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.