FOLFOX plus panitumumab or FOLFOX alone as additive therapy following R0/1 resection of RAS wild-type colorectal cancer liver metastases - The PARLIM trial (AIO KRK 0314).

PURPOSE: This trial investigates the addition of panitumumab to chemotherapy with fluorouracil/folinic acid and oxaliplatin (FOLFOX) in a 2:1 randomised, controlled, open-label, phase II trial in RAS wild-type colorectal cancer patients with R0/1-resected liver metastases. EXPERIMENTAL DESIGN: The primary endpoint was progression-free survival (PFS) two years after randomisation. The experimental arm (12 weeks of biweekly mFOLFOX6 plus panitumumab followed by 12 weeks of panitumumab alone) was considered active if the two-year PFS rate was ≥65%. Based on historical data, a two-year PFS rate of 50% was estimated in the control arm (12 weeks of biweekly FOLFOX). The trial was performed with a power of 80% and an alpha of 0.05. Secondary endpoints included overall survival (OS) and toxicity. The trial is registered with ClinicalTrials.gov, NCT01384994. RESULTS: The full analysis set consists of 70 patients (pts) in the experimental arm and 36 pts in the control arm. The primary endpoint was missed with a two-year PFS of 35.7% with FOLFOX plus panitumumab and 30.6% in the control arm. In comparative analyses, trends towards improved PFS (HR 0.83; 95%CI, 0.52-1.33; P = 0.44) and OS (HR 0.70; 95% CI, 0.34-1.46; P = 0.34) were observed in favour of the panitumumab-based study arm. No new or unexpected safety signals were observed with FOLFOX plus panitumumab following liver resection. CONCLUSION: The PARLIM trial failed to demonstrate a two-year PFS rate of 65% after resection of colorectal liver metastases. The positive trends in survival endpoints may support future trials evaluating treatment with anti-EGFR agents after resection of liver metastases.

Final results from IMPROVE: a randomized, controlled, open-label, two-arm, cross-over phase IV study to determine patients' preference for everolimus in combination with exemestane or capecitabine in combination with bevacizumab in advanced HR-positive, HER2-negative breast cancer.

BACKGROUND: The objective of the IMPROVE study was patients' preference for either endocrine-based therapy or combined chemo- and anti-angiogenic therapy in advanced HR-positive/HER2-negative breast cancer. METHODS: In this randomized, cross-over phase IV study, 77 patients were recruited in 26 sites in Germany. Patients were randomized 1:1 to receive either capecitabine plus bevacizumab (Cap+Bev) as first-line therapy followed by cross-over to everolimus plus exemestane (Eve+Exe) as second-line therapy (Arm A) or the reverse sequence (Arm B). The primary endpoint was patients' preference for either regimen, assessed by the Patient Preference Questionnaire 12 weeks after cross-over. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QoL). RESULTS: 61.5% of patients preferred Cap+Bev (p = 0.1653), whereas 15.4% preferred Eve+Exe and 23.1% were indecisive. Physicians showed a similar tendency towards Cap+Bev (58.1%) as the preferred regimen versus Eve+Exe (32.3%). Median first-line PFS was longer for Cap+Bev than for Eve+Exe (11.1 months versus 3.5 months). Median second-line PFS was similar between Cap+Bev and Eve+Exe (3.6 months versus 3.7 months). Median OS was comparable between Arm A (28.8 months) and Arm B (24.7 months). 73.0% and 52.6% (first-/second-line, Cap+Bev) and 54.1% and 52.9% (first-/second-line, Eve+Exe) of patients experienced grade 3/4 TEAEs. No treatment-related deaths occurred. QoL and treatment satisfaction were not significantly different between arms or treatment lines. CONCLUSIONS: Patients tended to favor Cap+Bev over Eve+Exe, which was in line with physicians' preference. Cap+Bev showed superior first-line PFS, while QoL was similar in both arms. No new safety signals were reported. TRIAL REGISTRATION: EudraCT No: 2013-005329-22. Registered on 19 August 20.