Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial.

Background: Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods: Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results: Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions: Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov: NCT00790036.

A phase II randomized study comparing navelbine and capecitabine (Navcap) followed either by Navcap or by weekly docetaxel in the first-line treatment of HER-2/neu negative metastatic breast cancer.

UNLABELLED: Following the proven efficacy and tolerability of Navcap and Navcap followed by docetaxel in the treatment of MBC, a phase II randomized study was initiated to assess the ORR of both arms in the first-line setting of MBC. Patients with no prior chemotherapy for MBC and HER-2/neu negative were eligible. All patients received Navcap (V 25 mg/m2 on d1 and d8 and C 825 mg/m2 bid D1-14 q3w) for a total of 4 cycles. Patients progressing under Navcap were withdrawn and received docetaxel as second-line treatment. Patients responding or stable were randomized to 2 arms: 4 cycles of Navcap (A) or 12 weekly docetaxel (25 mg/m²/week) (B). From July 2004 to July 2008, a total of 106 patients were enrolled. Ninety-four patients were evaluable before randomization, with a clinical benefit of 58%. Twenty-one patients (22%) had disease progression and were therefore not randomized. Forty-one patients were randomized to arm A and 29 patients to arm B. ORRs were 56 and 71% in arms A and B, respectively. The median time to progression and overall survival were 10 and 35 months in arm A and 12 and 37 months in arm B. Adverse events were mild. Arm A: grade 3-4 neutropenia (10%), grade 3 anemia (5%). Arm B: grade 3 neutropenia (6%), grade 3 anemia (6.2%), and grade 2 alopecia (12%). CONCLUSION: Both Navcap and Navcap followed by Docetaxel regimens were tolerated with manageable toxicity, offering consistent activities in terms of response rate for metastatic breast cancer patients.