Cohort 1 had been diagnosed between 2006 and 2007 and had been treated with bevacizumab-carboplatin-paclitaxel therapy. Cohort 2 had been diagnosed in the same period, but had been treated with carboplatin-paclitaxel therapy. Finally, Cohort 3 had been diagnosed earlier (2002-2005) and had received carboplatin-paclitaxel therapy. The data were analyzed to calculate overall survival as measured from the first date of chemotherapy treatment until death, or the end of 2009, whichever event came sooner.
Although there were differences in median survival between cohorts, the differences were not statistically significant (Cohort 1, 9.7 months; Cohort 2, 8.9 months; Cohort 3, 8.0 months). One-year survival probabilities were 39.6% (95% CI, 34.6%-45.4%) for Cohort 1 vs 40.1% (95% CI, 37.4%-43.0%) for Cohort 2, and 35.6% (95% CI, 33.8%-37.5%) for Cohort 3. Further statistical analysis failed to demonstrate a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts. These findings led the investigators to conclude that adding bevacizumab to carboplatin and paclitaxel does not prolong survival for patients with advanced NSCLC.
In another study, the safety and efficacy of first-line bevacizumab in combination with standard chemotherapy was again evaluated.4 This international, open-label, single-arm study involved 2,212 patients aged 65 years or older with advanced or recurrent NSCLC. Patients received up to six cycles of bevacizumab (7.5 or 15mg/kg) plus any standard of care chemotherapy until they reached the point of disease progression or toxicity. Subgroup analysis by age showed the incidence of adverse events (AEs) was similar for both elderly and younger patients (bleeding 38.2% vs. 38.3%; hypertension 33.1% vs. 30.6%; proteinuria 33.4% vs. 29.3%). Median overall survival was similar in elderly and younger patients (14.6 months, both age groups), as was time to disease progression (TTP; 8.2 vs. 7.6 months), response rate (49.3% vs. 52.4%), and disease control rate (89.3% vs. 88.4%). The main conclusion was that, compared with their younger counterparts, patients with NSCLC aged 65 years or older experienced a similar survival benefit with first-line bevacizumab and at minimal toxicity.
Adding bevacizumab to a cocktail of gemcitabine/cisplatin was the aim in a multicenter, double-blind, placebo-controlled randomized phase 2 trial in patients with previously untreated, unresectable malignant mesothelioma (MM), a deadly form of lung cancer that is generally treated with platinum-based chemotherapy.5
In a complex dosing scheme, patients with high ECOG performance scores received six cycles of the following regimen: gemcitabine 1,250mg/m2 on days 1 and 8, every 21 days; cisplatin 75mg/m2 every 21 days; and bevacizumab 15mg/kg or placebo every 21 days until they reached the primary end point of progression-free survival (PFS). For the 108 evaluable patients, bevacizumab did not significantly prolong survival vs placebo (6.9 months vs. 6.0 months, P =0.88), which led to the conclusion that addition of bevacizumab had no survival benefit in this patient population.
Finally, a phase 2 clinical trial evaluated the synergistic effects and safety of bevacizumab-topotecan combination therapy.6 This was an open-label, interventional trial in patients with stage IIIB/IV NSCLC who had failed prior systemic chemotherapy. Bevacizumab was administered 10mg/kg/day IV on days 1 and 15, following topotecan administration until the primary end point (disease progression) was met. Topotecan 4mg/m2 IV was administered on days 1, 8, and 15, with a rest on day 22. Treatment was repeated every 28 days. This trial has been completed, but data have not yet been published.