11.9 weeks; hr: 0.86; 95% ci: 0.69 to 1 1.06) and os (10.5 months vs. require validation, however. All of the oral antiangiogenic agents result in added toxicities. Some agents have resulted in an increased risk of death, limiting their development. Available evidence supports a limited number of antiangiogenic therapies for patients with nsclc, but no biomarkers to help in patient selection are currently available, and additional translational research is needed to identify predictive biomarkers for antiangiogenic therapy. 200410Randomized200611 (ECOG 4599)Phase IIICarboplatinCpaclitaxel with bevacizumab 15 mg/kg434356.212.3Not assessed.CarboplatinCpaclitaxel44415 201012 (AVAiL)Phase IIICisplatinCgemcitabine with bevacizumab 15 mg/kg35134.6201213 (JO19907)Randomized201314 (PointBreak)Phase IIICarboplatinCpemetrexed with bevacizumab 15 mg/kg, Elaidic acid followed by bevacizumabCpemetrexed472346.012.6Not assessed.CarboplatinCpaclitaxel with bevacizumab 15 mg/kg, followed by bevacizumab467335.6201415 (AVAPERL)Phase IIICisplatinCpemetrexed with bevacizumab 7.5 mg/kg, then randomized to maintenance37622. 7EORTC QLQ-30 and -LC13 identified no difference in global quality of life.201416Randomized201517 (BEYOND)Phase IIICarboplatinCpaclitaxel with bevacizumab 15 mg/kg138549.224.3Not assessed.CarboplatinCpaclitaxel with placebo138266.5201518 (PRONOUNCE)Phase IIICarboplatinCpemetrexed, followed by pemetrexed18223.63.9a10.5Not assessed.CarboplatinCpaclitaxel with bevacizumab 15 mg/kg, followed by bevacizumab17927.42.9a HR: 0.85; 90% CI: 0.70 to 1 1.0411.7201419Phase IICarboplatinCpaclitaxel with ramucirumab41557.8201520Randomized201421Phase IICisplatinCpemetrexedCaflibercept4226.35lung abscess, and chronic obstructive pulmonary disease. Six patients experienced major bleeding, with four fatalities. Major hemoptysis was associated Rabbit Polyclonal to TCF7 with squamous-cell histology, and subsequent clinical trials of bevacizumab in nsclc included only patients with nonsquamous histology, good performance status, and no history of thrombosis, bleeding, gross hemoptysis, or brain metastasis. The efficacy of bevacizumab in combination with chemotherapy in nsclc was first demonstrated in the Eastern Cooperative Oncology Group (ecog) 4599 trial11. Patients were randomized to carboplatinCpaclitaxel Elaidic acid either alone or with bevacizumab 15 mg/kg every 21 days. Overall survival (os) was improved for patients randomized to Elaidic acid carboplatinCpaclitaxel with bevacizumab [12.3 months vs. 10.3 months; hazard ratio (hr): 0.79; 95% confidence interval (ci): 0.67 to 0.92]. Significant improvements were also observed in the overall response rate Elaidic acid (orr) and progression-free survival (pfs). However, conflicting information about os has been observed in three other first-line trials evaluating the addition of bevacizumab to platinum-based chemotherapy in advanced nsclc12,13,17. Longer pfs was seen in the avail trial comparing cisplatinCgemcitabine with or without bevacizumab 7.5 mg/kg or 15 mg/kg. The final analysis failed to demonstrate any significant improvement in os for either dose of bevacizumab in combination with cisplatinCgemcitabine. The adverse effect profile in the avail trial was similar to that in ecog 4599. The addition of bevacizumab to chemotherapy is associated with significant, increased risks of neutropenia, febrile neutropenia, hyponatremia, hypertension, proteinuria, headache, rash, and bleeding events. Additional trials have evaluated platinum-based chemotherapy plus bevacizumab compared with other contemporary first-line treatments for advanced nsclc14,15. The randomized phase iii PointBreak trial compared two chemotherapy backbones: carboplatinCpemetrexed followed by maintenance pemetrexed, and carboplatinCpaclitaxel, both combined with bevacizumab 15 mg/kg14. In the pemetrexed arm, pfs was significantly prolonged (6.0 months vs. 5.6 months; hr: 0.83; 95% ci: 0.71 to 0.96), but that difference did not translate into any improvement in os. Related grades 3 and 4 neutropenia, febrile neutropenia, sensory neuropathy, and alopecia were significantly lower in the pemetrexed arm. The strategy of maintenance pemetrexed was also evaluated in the avaperl trial15. Patients with nonsquamous nsclc were randomized to bevacizumab maintenance, with or without pemetrexed, after first-line bevacizumabCcisplatinCpemetrexed. Prolonged pfs was observed with maintenance pemetrexed and bevacizumab (7.4 months vs. 3.7 months; hr: 0.48; 95% ci: 0.35 to 0.66), but no significant difference in os was seen (17.1 months vs. 13.2 months; hr: 0.87; 95% ci: 0.63 to 1 1.21). Currently, there.