Four-Drug Combination Shown to Be Safe and Effective for NSCLC

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.


Erbitux-Avastin Combination Plus Chemotherapy in Lung Cancer Is Safe and Effective

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.


Phase II Trial of Carboplatin, Paclitaxel, Cetuximab, and Bevacizumab Followed by Cetuximab and Bevacizumab in Advanced Nonsquamous Non-Small-Cell Lung Cancer: SWOG S0536

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.


Alimta Offers Only Limited Advantage in Lung Cancer Study

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.


New Nanopharmaceutical May Be Able to Overcome Resistance to Antiangiogenic Treatment

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.


PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followe…

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.


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.


ATLAS: Randomized, Double-Blind, Placebo-Controlled, Phase IIIB Trial Comparing Bevacizumab Therapy With or Without Erlotinib, After Completion of Chemotherapy, With Bevacizumab for First-Line Trea…

This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non–small-cell lung cancer (NSCLC).

The addition of erlotinib to bevacizumab significantly improved PFS but not OS. Although generally well tolerated, the modest impact on survival and increased toxicity associated with the addition of erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen will not lead to a new postchemotherapy standard of care.


Maintenance Therapy with Avastin-Alimta Combination Appears Effective in Advanced NSCLC

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.