Veliparib + Chemo Fails to Improve OS, PFS in Untreated NSCLC
Veliparib in combination with carboplatin and paclitaxel was well tolerated but did not significantly improve overall response rate, survival.
Veliparib in combination with carboplatin and paclitaxel was well tolerated but did not significantly improve overall response rate, progression-free survival, or overall survival compared with chemotherapy alone among patients with previously untreated advanced or metastatic non-small cell lung cancer (NSCLC), according to a study published in Clinical Cancer Research.1
Veliparib is a poly(ADP-ribose) polymerase (PARP) -1 and -2 inhibitor that has been shown to enhance the efficacy of platinum agents. Researchers assessed the efficacy and tolerability of veliparib combined with carboplatin and paclitaxel in NSCLC.
For the multicenter, double-blind, phase 2 trial (ClinicalTrials.gov Identifier: NCT01560104), investigators enrolled 158 treatment-naive patients with stage IIIB or IV NSCLC, of whom 48% had squamous histology. Participants were randomly assigned 2:1 to receive veliparib plus carboplatin and paclitaxel or chemotherapy alone for up to 6 cycles.
No significant difference in progression-free survival was observed between the 2 groups. Median progression-free survival was 5.8 months with veliparib compared with 4.2 months with placebo (hazard ratio [HR], 0.72; 95% CI, 0.45-1.15; P = .17), thus not meeting the study's primary endpoint.
Median overall survival was 11.7 months in the veliparib arm versus 9.1 months in the placebo group (HR, 0.80; 95% CI, 0.54-1.18; P =.27); the overall response rate was 32.4% and 32.1%, respectively, and there was no significant difference in duration of response (HR, 0.47; 95% CI, 0.16-1.42; P = .18).
Subgroup analyses demonstrated no significant difference in progression-free (HR, 0.54; 95% CI, 0.26-1.12; P = .098) or overall survival (HR, 0.73; 95% CI, 0.43-1.24; P = .24) among patients with squamous histology, though the authors note that both endpoints favored veliparib.
The rates of grade 3 to 4 neutropenia, thrombocytopenia, and anemia were also similar between the 2 treatment arms.
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Despite no significant differences in outcomes between the groups, the investigators observed a trend toward improved progression-free survival and overall survival with veliparib plus chemotherapy.
Researchers are assessing the combination in the same treatment setting in a phase 3 trial (ClinicalTrials.gov Identifier: NCT02106546).
- Ramalingam SS, Blais N, Mazieres J, et al. Randomized, placebo-controlled, phase 2 study of veliparib in combination with carboplatin and paclitaxel for advanced/metastatic non-small cell lung cancer. Clin Cancer Res. 2016 Oct 10. doi: 10.1158/1078-0432.CCR-15-3069 [Epub ahead of print]