350 Background: Nab-paclitaxel plus gemcitabine regimen (NABGEM) became a standard in first-line patients (pts) with metastatic pancreatic adenocarcinoma (mPAC). The AFUGEM trial evaluated the efficacy and safety of nab-paclitaxel plus simplified LV5FU2 (NABFU). Methods: Main eligibility criteria were: untreated mPAC, ECOG PS≤2. Pts received nab-paclitaxel (125 mg/m 2 on d1, 8 and 15) plus gemcitabine (1000 mg/m 2 on d1, 8 and 15) or plus simplified LV5FU2 (leucovorin 400 mg/m 2 , 5FU bolus 400 mg/m 2 followed by 2400 mg/m 2 given as a 46-hour continuous infusion on d1 and 15), one cycle every 4 weeks in both arms, ratio 1:2, respectively. The primary end point was observed progression-free survival (PFS) rate at 4 months (m). A Fleming 2-stage design was used with a targeted (H1) 4m-PFS rate of 50% in NABFU arm and an uninteresting 35% rate (H0, unilateral alpha of 5% and power of 80%). Results: 114 pts were included: NABGEM n=39, NABFU n=75. Baseline characteristics were well balanced: median age 66 years (45-86), ≥2 metastatic sites 36.8%, ECOG PS 0-1 84.2% and 2 15.8%, at the exception of pain more frequent in the NABFU arm (38.5% vs 56.0%). In mITT population, the observed 4m-PFS rates were of 55.4% [95% CI, 45-63] in NABFU Vs 53.9% [95% CI, 39.6-67.7] in NABGEM. Disease control rates were 65% (95% CI, 53-76) and 62% (95% CI, 45-77) respectively. After a follow-up of 24.3m, median PFS were 5.9 [95% CI, 3.6-7.4] v 4.9 months [95% CI, 2.1-7.7] [HR=0.79, 95% CI: 0.52-1.20]. Grade 3-4 adverse events were more frequent in NABGEM (77% v 87%). At tumor progression, in the NABFU arm, 50 patients (66%) and then 13 patients (17%) received a second and third line of chemotherapy respectively, versus 22 patients (56%) and 6 patients (15%) in the NABGEM arm. Median OS were 11.4 [95% CI, 8.8-16.5] v 9.2 months [95% CI, 6.0-13.6] [HR=0.61, 95% CI: 0.40-0.95], respectively. The 12 and 18-months OS rates in NABFU vs NABGEM arm were 48% Vs 41% and 34% Vs 13%, respectively. Conclusions: Nab-paclitaxel plus simplified LV5FU2 appears at least as active as gemcitabine plus nab-paclitaxel in mPAC. The toxicity profile is safe and tolerable. This regimen deserves evaluation in a phase III trial. Clinical trial information: NCT01964534.
700 Background: Pts with aPDAC often have general health impairment due to high symptom burden at diagnosis. We investigated prospectively the clinical benefit (CB) of an EISCP followed by CTx as early as suspicion of aPDAC in pts with ECOG performance status (PS)≥2. Methods: In this multicenter study, PS≥2 pts with pathologically confirmed or suspected aPDAC on imaging were included at first oncology visit (V1) in a personalized 14-d EISCP including pain, nutritional, diagnostic/stenting procedures. Post-EISCP PS≤1 pts received mFOLFIRINOX or gemcitabine(Gem)/Nab-paclitaxel(NP), PS≥2 received mFOLFOX7 or investigator choice CTx or best supportive care (BSC). The primary endpoint was the 14-EISCP success on both feasibility of procedures within 14-d±2 and CB defined by post-EISCP PS≤1, ≥5 points improvement of either fatigue/pain/global health EORTC QLQ-C15-PAL quality of life (QOL) scores, or CTx start ≤30d, aiming 59% success for clinical relevance. Secondary endpoint included uni/multivariate median overall survival (mOS) analyses. Results: As of 07/2022, 106 pts were included; 93 pts were evaluable for primary endpoint: male 46%, mean age 74 yrs, PS2/3 79%/21%, metastases (M1) 62%, pathological diagnosis needed 53%, biliary stenting 16%. V1 mean QOL global health score was 48±23. mOS was 4.1 months (IC95 2.8-5.7). The 14-d feasibility was achieved in 71%. Post-EISCP CB was observed in 82% of pts: 13%, PS improvement to 0/1, 23% QOL improvement and/or 73% CTx start ≤30-d. Eight pts (9%) died during the EISCP. The primary endpoint was achieved in 59% of pts (n=55). Overall, 17 pts (16%) received mFOLFIRINOX/GemNP, 32 (30%) FOLFOX, 29 (27%) Gem or 5FU alone, and 28 (27%) BSC. OS analyses are shown. At d30, pts receiving CTx had a mean change of QOL global health score from 51±23 to 60±23. Conclusions: In PS≥2 pts with aPDAC, a personalized 14-EISCP is feasible and lead to a meaningful CB allowing the administration of doublet/triplet CTx in nearly half of the pts. Pts starting CTx within 30d had improved OS. Clinical trial information: NCT02979483 . [Table: see text]
The phase II AFUGEM GERCOR trial aimed to assess the efficacy of a first-line therapy combining nab-paclitaxel plus either gemcitabine (gemcitabine group) or simplified leucovorin and fluorouracil (sLV5FU2 group) in patients with previously untreated metastatic pancreatic cancer. Results of progression-free survival at 4 months (primary endpoint) were in favor of the sLV5FU2 group. This paper presents health-related quality of life (HRQoL) data as a secondary endpoint.HRQoL was assessed using the EORTC QLQ-C30 questionnaire at baseline and at each chemotherapy cycle until the end of treatment. The HRQoL deterioration-free survival (QFS) was used as a modality of longitudinal analysis. QFS was defined as the time between randomization and the first definitive HRQoL score deterioration as compared to the baseline score, or death. Sensitivity analysis was performed excluding death as an event. Univariate Cox models were used to estimate hazard ratios (HRs) and 90% confidence intervals (CIs) of the treatment effect.Between 2013 and 2014, 114 patients were randomized in a 1:2 ratio (39 in the gemcitabine group and 75 in the sLV5FU2 group). Patients in the sLV5FU2 group seemed to present longer QFS than those of the gemcitabine group for 14 out of 15 dimensions, with HRs < 1. Results of the sensitivity analysis excluding death as an event were significantly in favor of the sLV5FU2 group for physical functioning (HR = 0.51 [90% CI 0.27-0.97]) and pain (HR = 0.26 [90% CI 0.09-0.74]).The nab-paclitaxel plus simplified leucovorin and fluorouracil combination had no negative impact in exploratory HRQoL analyses.
LBA3500^ Background: Therapy targeting VEGF or EGFR demonstrated clinical activity in combination with chemotherapy (CT) in mCRC but monoclonal antibodies cannot be associated. The DREAM trial compares a maintenance therapy (MT) with bev +/- EGFR tyrosine kinase inhibitor erlotinib (E) after a first-line Bev-based induction therapy (IT) in pts with mCRC. Methods: Pts with previously untreated and unresectable mCRC were eligible. After a Bev-based IT with FOLFOX or XELOX or FOLFIRI, pts without disease progression were randomized to MT between Bev alone (Bev 7.5 mg/kg q3w; arm A) or Bev+E (B 7.5 mg/kg q3w, E 150 mg/day continuously; arm B). Pts were treated until progression or unacceptable toxicity. The primary endpoint was PFS on MT. Results: The study enrolled 700 pts from 01/2007 to 11/2011 in 3 countries (France, Canada, Austria). 446 (63.7%) pts were randomized for MT (arm A, N=224; arm B, N=222). Among the 446 randomized pts, IT regimen was FOLFOX-Bev in 265 pts (59.4%), XELOX-Bev in 135 pts (30.3%), and FOLFIRI-Bev in 46 pts (10.3%). Baseline characteristics of randomized pts were (arm A/B): ECOG PS 0, 60% in both arms; normal LDH level 47%/49%; normal alkaline phosphatase level 48%/50%; synchronous metastasis 83%/82%. The median no of MT cycles was 6 in both arms. With a median follow-up of 31.0 months, 327 PFS events were observed. Median MT-PFS were 4.6 m in arm A vs 5.8 m in arm B (HR 0.73 [95%CI: 0.59-0.91], P=.005). Median PFS from inclusion were 9.2 m vs 10.2 m. During MT, in arm A vs arm B, grade 3-4 diarrhea (<1% vs 9%) and grade 3 skin toxicity (0% vs 19%) were the main differences in toxicity. Severe adverse events from randomization related to B or E were 6 in arm A and 7 in arm B. Overall survival is not mature. Conclusions: The addition of erlotinib to bevacizumab after induction therapy significantly improves the duration of maintenance PFS, following induction with first-line chemotherapy plus bevacizumab, in patients with unresectable metastatic colorectal cancer.
LBA3500^ The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
