No abstract

clinicaltrials.gov Identifier: NCT02295930.

This study shows that palonosetron in combination with aprepitant and dexamethasone is effective to prevent chemotherapy-induced nausea and vomiting in patients treated with cisplatin-based HEC.

BackgroundColorectal cancer patients have a median age of incidence >65years although they are largely under-represented in phase-III trials. This large population contains patients unfit for treatment, those suitable for monotherapy or for doublets and the impact of chemotherapy outside clinical trial is unclear. The aim of the study was to retrospectively analyse Overall Survival(OS) of elderly metastatic colorectal cancer(mCRC) patients treated with chemotherapy in daily practice.MethodsKaplan-Meir method was used for OS, the log-rank or Tarone-Ware test for differences between subgroups, Cox’s proportional hazard model to assess the impact of known prognostic factors and treatment.Results751 patients with mCRC observed between January 2000 and January 2013 were collected. Median age was 79 year(75–93); Male/Female 61/39%, ECOG-PS 0-1/2 85/15%; colon/rectum 74/26%; multiple metastatic sites 34%, only liver metastasis in 41% of patients. KRAS status was studied in 35% of patients: 44% of them showed gene mutation. 20.5% of patients did not received any kind of treatment including surgery. Comorbidities observed: cardiovascular 34%, diabetes 14%, hypertension 50%. Primary tumor was resected in 80.6%; surgery of liver metastasis was done in 19% of patients (2.3% of patients >80years). 78% of patients underwent chemotherapy. Median follow up was 12 months(range 1–124). Median OS was 17 months (CI 95%15–19);median OS in no-treated patients was 5 months (4–6); mOS of patients with at least one treatment was 20 months (18–22). In KRAS mutated group median OS was 19months (15–23) while in KRAS wild type patients median OS was 25 months (20–30). At multivariate analysis sex(Female), age(<80y), performance status(0–1), chemotherapy, Surgery of metastasis, Surgery of primary tumor and Site of metastasis(liver) were prognostic factors for OS.ConclusionThe results of our study show that in clinical practice treatment has a positive impact on OS of elderly patients, confirmed at multivariate analysis, included patients with age >80 years old or with a poor performance status (respectively p<0.0001 and p<0.0001). KRAS analysis deserve further evaluation.

3508 Background: In the phase III TRIBE study FOLFOXIRI/bev significantly improved Response Rate (RR), PFS and OS when compared with FOLFIRI/bev as initial treatment of mCRC. However, the actual advantage by the triplet could be lower when compared with a pre-planned sequential strategy of doublets (FOLFOX, FOLFIRI). TRIBE2 (NCT02339116) is a phase III trial in which unresectable mCRC pts were randomized 1:1 to FOLFOX/bev followed by FOLFIRI/bev after PD (arm A) or FOLFOXIRI/bev followed by the reintroduction of the same regimen after PD (arm B). A pre-planned interim analysis showed a significant advantage for arm B in terms of PFS2, primary endpoint of the study, defined as the time from randomization to PD on any treatment given after first PD or death (PD2). Methods: The study had 80% power to detect a HR for PFS2 of 0.77 in favor of arm B with an overall 2-sided-α error of 0.05 (0.0131 and 0.0455 for the interim and final analyses, planned at 303 and 466 PFS2 events, respectively). Secondary endpoints included RR, 1st-PFS, i.e. the time from randomization to the first evidence of PD or death (PD1), 2nd-PFS, i.e. the time from PD1 to PD2, and OS. Results: From February 2015 to May 2017, 679 pts (arm A/B: 340/339) were enrolled in 58 Italian sites. Main pts’ characteristics were (arm A/B): right side 38%/38%, synchronous mets 89%/89%, RAS mutant 65%/63%, BRAF mutant 10%/10%. At a median follow up of 30.6 mos, 514 (arm A/B: 272/242) PD2, 594 (arm A/B: 303/291) PD1 and 408 (arm A/B: 217/191) OS events were collected. A significant advantage by upfront FOLFOXIRI/bev was confirmed in terms of PFS2 (19.1 vs 16.4 mos, HR 0.74, 95%CI 0.62-0.88, p<0.001), RR (62% vs 50%, OR 1.61, 95%CI 1.19-2.18, p=0.002) and 1st-PFS (12.0 vs 9.8 mos, HR 0.75, 95%CI 0.63-0.88, p<0.001). A significant OS benefit for pts in arm B was also observed (27.6 vs 22.6 mos, HR: 0.81, 95%CI: 0.67-0.98, p=0.033). Out of 594 pts with a PD1 event, 470 (79%, arm A/B: 251/219) received a treatment after PD. In the per-protocol analysis (N=323), pts in arm B showed significantly longer 2nd-PFS (6.5 vs 5.8 mos, HR 0.76, 95%CI 0.59-0.97, p=0.024). Conclusion: Upfront FOLFOXIRI/bev followed by the pre-planned reintroduction of the same agents after PD provided a statistically significant and clinically relevant PFS2 and OS benefit when compared with the pre-planned sequential administration of FOLFOX/bev and FOLFIRI/bev in unresectable mCRC patients. A median OS of 27.6 mos was reached despite the high percentage of pts with poor prognostic features ( RAS and BRAF mutations, right side, synchronous mets). Clinical trial information: NCT02339116.