Here is DNA's abstract on VEGF that tries to absolve the lung bleeding episodes and highlights efficacy by slicing squamous from non-squamous NSCLC. Is this really persuasive? (Not to me, BWDIK). Thoughts appreciated.
Carboplatin (C) + Paclitaxel (T) + RhuMab-VEGF (AVF) May Prolong Survival in Advanced Non-Squamous Lung Cancer.
D. H. Johnson, R. DeVore, F. Kabbinavar, R. Herbst, E. Holmgren, W. Novotny, Vanderbilt-Ingram Cancer Center, Nashville, TN; UCLA, Los Angeles, CA; M.D. Anderson Cancer Center, Houston, TX; Genentech, South San Francisco, CA.
VEGF is an endothelial mitogen secreted by tumors & critical to new vessel formation. In murine tumor models, antibody directed against VEGF reduces tumor growth in a dose dependent manner. When given with chemotherapy, additive cytotoxicity is observed. In a previously reported multicenter randomized phase II trial (PASCO 19:485a, 2000), CT + AVF [humanized murine antibody to VEGF] improved objective response rates (ORR) & time to progression (TTP) in advanced NSCLC. However, life-threatening hemorrhage (LTH) developed in 6/66 AVF-treated pts & 4 died. In an evaluation of potential risk factors, squamous histology (SQ) (P=0.004) & AVF treatment (P=0.082) were the only factors associated with LTH. A subset analysis of non-squamous (non-SQ) pts was performed to ascertain the impact of AVF on ORR & TTP & to estimate MST. These parameters were compared to that observed with CT alone in this study & that observed with CT alone in 2 recently completed cooperative group trials (E1594 & S9509). 53/78 pts with non-SQ histology received AVF (low-dose: 22; high-dose: 31 pts). 2 (3.8%) AVF-treated non-SQ pts had LTH. 14 non-SQ pts progressing on CT alone were crossed over to AVF & 3 received treatment for $6 mo. ORR & TTP favored the AVF-treated non-SQ pts . MST for the non-SQ population was improved in both AVF dose groups & compared favorably with that achieved with CT alone in E1594 & S9509. In the control arm, TTP is identical to that observed in E1594 & S9509 but MST is superior, possibly due to crossover. Thus, in AVF-treated non-SQ pts, a significant benefit is suggested across all the efficacy endpoints, most notable survival, in spite of pt crossover. These findings are reminiscent of those seen in breast cancer with trastuzumab + chemotherapy & suggest AVF may prolong survival in non-SQ NSCLC pts without engendering unacceptable toxicity or an excess of toxic deaths. Confirmatory studies are needed.
Wilder |
