Background Non-metastatic pancreatic ductal adenocarcinoma (PDAC) presents a challenging scenario: the rarity of the disease, the limited number of completed prospective trials, and the shortcomings of comparability across series produce several controversial topics and unanswered questions. Guideline recommendations usually include all the different therapeutic options, de facto transferring to the multidisciplinary team the responsibility on the final decision. This secondary analysis of the GARIBALDI study was aimed to explore the correlation of center type, self-declared volume, and commitment with the overall survival (OS) in patients with non-metastatic PDAC. Patients and methods Treatment-na & iuml;ve patients aged >= 18 years with a pathological diagnosis of non-metastatic PDAC, enrolled between July 2017 and October 2019, were analyzed. OS was defined as the time from treatment start to death. The impact of centers and clinical-demographic characteristics on OS was evaluated using Cox models. Results Overall, 402 patients enrolled in 41 centers were eligible for this analysis. The median age was 68.4 years (range 35.6-88.8 years), 49.5% were females, 93.5% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, 16.7% had prior cancer history, and the median CA 19-9 level was 171.5 IU/ml (first-third quartile 24.5-937.5 IU/ml). For 79.8% of patients treatment started within 1 month from diagnosis. Thirty six point six percent of patients underwent upfront surgery and 91.8% of these received a subsequent adjuvant chemotherapy; 14.2% received chemotherapy followed by surgery and 49.3% chemotherapy without surgery. The preferred chemotherapy schemes were gemcitabine (54.8%) for adjuvant chemotherapy and nab-paclitaxel + gemcitabine (55.3%) for upfront chemotherapy. The median follow-up was 57.6 months and 300 patients died. A statistically significant shorter OS was observed in both low- [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.12-2.32, P = 0.0099] and medium-commitment (HR 1.57, 95% CI 1.10-2.23, P = 0.0120) compared to high-commitment institutions, when adjusting for clinically relevant covariates. Conclusion The GARIBALDI study suggests that the volume and the academic brand are not associated with OS in patients with non-metastatic PDAC, while center commitment warrants further exploration.

This analysis from the GARIBALDI study was aimed to address the role of center self-declared expertise, type and commitment on the overall survival (OS) of patients with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC). Treatment-naive patients >= 18-year with pathological diagnosis of mPDAC were enrolled. OS was defined as the time from chemotherapy start to death from any cause. The impact of clinical-demographic and centers characteristics on OS was evaluated using Cox models. Between July 2017 and October 2019, 473 patients enrolled in 43 centers were eligible for this analysis. Median age was 69.3 (first-third quartile 61.2-74.5); 46.1 % females; 90.8 % ECOG PS 0-1; 67.4 % had liver metastases; median CA19.9700.5 UI/mL (first-third quartile 77.5-6629.5). For 37.1 % of patients chemotherapy started <4 weeks from diagnosis; 69.9 % of patients received nab-paclitaxel + gemcitabine; 16.9 % gemcitabine alone; 7.6 % FOLFIRINOX. The median follow-up was 51.8 months and 428 patients died. No statistically significant role of the type of institution was observed. Additionally, no statistically significant role of neither the self-declared expertise nor the accrual rate was observed. The GARIBALDI study suggests that the self-declared center expertise and the academic brand are not associated to OS in patients with mPDAC, while center commitment warrants further exploration. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The present analyses from the GARIBALDI was aimed to addressing the role of oncology center volume, type and accrual rate on the prognosis of patients (pts) with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC). Consenting treatment-naïve pts ≥ 18-year with pathological diagnosis of mPDAC were enrolled. Participating centers were categorized according to the self-declared expertise, the type and the accrual rate. Survival curves were estimated by the Kaplan–Meier method and compared by the log-rank test. Overall Survival (OS) was defined as the time from the date of medical therapy start to death for any cause. Between July 2017 and October 2019, 475 pts enrolled in 44 centers were eligible for these analyses. Median age was 69 (range 36-90); 46% females; 90% ECOG PS 0-1; 38% overweight/obese; 66% with liver metastases; median CA19.9 789 (range 0-1,374,500); 8% with prior PDAC resection; 17% with prior cancer history. Median time from diagnosis to treatment was 33 days. 65.2% of pts started therapy >25 days from baseline CT; 70.7% of pts received nab-paclitaxel+gemcitabine; 16.7% gemcitabine alone; 7.7% FOLFIRINOX; 37% received a second-line therapy. The median follow-up was 50 months and 405 pts died. The table provide the median OS estimates. Table: 1664PDeaths/NOverall survival (Median [95%CI])Log-rank p-valueSelf-declared expertise0.24483Low-volume (<25 pts/year)50/587.3 [5.6-9.0]Medium-volume (25-50 pts/year)101/1258.8 [6.7-11.5]High-volume (>50 pts/year)234/26710.1 [9.1-11.2]Type0. 3610Community hospitals183/2247.9 [6.7-9.6]Academic centers222/25110.1 [9.1-11.2]Accrual rate0.6348Low-accrual (<10 pts/year)173/2107.9 [6.7-9.5]Medium-accrual (10-50 pts/year)173/2019.6 [8.5-11.2]High-accrual (> 50 pts/year)59/6412.0 [9.7-14.9] Open table in a new tab Although not statically significant, the GARIBALDI survey detected a clinical difference in OS based on center volume, type, and accrual rate.

Background: Information about the adherence to scientific societies guidelines in the 'real-world' therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM).Patients and methods: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented.Results: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine + capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel + gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nab-paclitaxel + gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months).Conclusions: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

Trotabresib (TROTA) is a novel bromodomain and extraterminal protein inhibitor that has shown brain tumor tissue penetration, encouraging tolerability and preliminary efficacy in combination with standard of care (SOC) concomitant TMZ + RT and adjuvant TMZ in pts with ndGBM. We present long-term follow-up for part A (dose escalation) and an update on part B (expansion) of the ph 1b/2 CC-90010-GBM-002 study (NCT04324840). Study design has been previously described (Vieito et al. SNO 2022 . Abstr CTNI-21). Part B enrolled pts with IDH wild-type ndGBM; pts were randomized 2:1 to TROTA + SOC then maintenance TROTA (arm A) vs SOC alone (arm B). As of 20 Jan 2023, part A has closed with 32 pts enrolled (concomitant, n = 14; adjuvant, n = 18); part B has enrolled 136 pts (arm A, n = 91; arm B, n = 45). In part A, no new safety events were observed with longer follow-up; median follow-up was 21.6 mo (range 3.4–27.6). The most frequent grade (G) 3/4 treatment-related adverse event (TRAE) was thrombocytopenia (8/14 pts [57%] in the concomitant group and 9/18 pts [50%] in the adjuvant group). Efficacy in part A is shown in the table. At last follow-up, 8 pts (4 per group) remained on treatment, including 1 pt with ongoing complete response at cycle 24. In part B, the most common all-cause G 3/4 AE was thrombocytopenia occurring in 21/88 (24%) and 5/43 (12%) patients in arms A and B, respectively. TRAEs related to TROTA led to treatment discontinuation in 3 pts (arm A), and TRAEs related to TMZ led to discontinuation in 4 pts (2 in each arm); no treatment-related deaths reported. Enrollment of part B was recently completed; efficacy data are not yet mature. Addition of TROTA to SOC followed by maintenance TROTA in pts with ndGBM was well tolerated with no new safety signals in parts A and B, and promising efficacy in part A. Follow-up is ongoing.

Purpose Transarterial embolization of renal artery branches (RTE) is a minimally invasive procedure commonly performed in life-threatening renal bleeding of different etiologies. Despite the widespread use of RTE, no consensus guidelines are currently available. Our aim was to investigate clinical and technical efficacy and to identify potential predictors for clinical failure of this procedure. Methods All the RTE procedures performed in our Interventional Radiology unit in last 10 years were retrospectively collected and analyzed. All selected patients underwent both pre-procedural computed tomography angiography (CTA) and post-procedural CTA within 30 days. Clinical success was considered as primary endpoint. Demographic, laboratory, and diagnostic findings predictive of clinical failure of RTE were identified. Results Over a total of 51 patients enrolled, 27 (53%) were females and 33 (64.7%) had a renal bleeding of iatrogenic origin. Technical and clinical success was 100% and 80.4%, respectively. Hematoma volumes > 258.5 cm 3 measured at CTA, higher pre- and post-procedural serum creatinine (Scr) levels, an increase in Scr value > 0.135 mg/dl after the procedure, a worse post-procedural estimated glomerular filtration rate (eGFR), a post-procedural reduction of eGFR < 3.350 ml/min, and a post-procedural reduction of platelet count (PLT) > 46.50 × 10 3 /mmc showed a significantly higher rate of clinical failure. Conclusion RTE is a safe and effective procedure in the management of acute renal bleeding of various origins. Hematoma volume, Scr, PLT, and eGFR values were found to be predictive factors of poor clinical outcome and should be closely monitored.

e16278 Background: g BRCA mutations are found in approximately 8% of Italian PC pts screened within 3 months from diagnosis. g BRCA PC pts display enhanced sensitivity to platinum-based chemotherapy (CHT) and PARP inhibitors, such as olaparib. In metastatic g BRCA PC pts, maintenance olaparib after platinum-based CHT doubled PFS and resulted in twice as many long-term (3-yr) survivors (34% versus 18%) in the randomized POLO trial. However, despite guideline recommendations, olaparib is currently not reimbursed in Italy in metastatic g BRCA PC pts, based on the absence of significant differences in median OS. Methods: We analyzed the impact of exposure to olaparib on OS from the start of I-line treatment in a cohort of 114 Italian g BRCA PC pts, whose clinical characteristics and outcomes in response to first () and subsequent chemotherapy lines have been previously reported ( 10.1016/j.esmoop.2021.100238 ; 10.1038/s41416-022-02086-w ). Results: Clinical characteristics of patients who did or did not receive olaparib were well balanced, except for baseline CA19.9 levels (significantly lower in patients who received olaparib, p=0.043) and exposure to platinum-containing chemotherapy (significantly less in patients who did not receive olaparib, p<0.0001). In the entire cohort of g BRCA PC pts, OS from the start of I-line treatment for metastatic disease was significantly (p=0.02) longer in pts who had been exposed to olaparib in any treatment line (n=53). Since previous surgery and response to I-line chemotherapy were strong independent predictors of OS at multivariate analysis, we analyzed pts who were diagnosed with stage IV (M+, n=87) disease and pts who did not experience PD as best response to I-line chemotherapy (no PD, n=94), separately. A statistically significant difference in OS favoring g BRCA PC pts who were exposed to olaparib in any line of treatment was observed in the M+ cohort (p=0.0025), in the no PD cohort (p=0.049), but not in the M+/no PD cohort (n=73, p=0.057) or in the POLO-like population (I-line maintenance; n=60, p=0.334). Conclusions: In g BRCA PC pts, exposure to olaparib in any line of treatment in a real-world setting significantly impacts on OS; timing and setting of administration remain to be determined in order to optimize survival advantage. [Table: see text]

2522 Background: The phase I GATTO study explored the feasibility, tolerability and preliminary activity of combining Gatipotuzumab (GAT), a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin-1 (TA-MUC1), and an anti-EGFR antibody. Preclinical evidence suggests a complex interaction between TA-MUC1 and EGFR on the cell surface of epithelial tumors and synergistic antibody dependent cell cytotoxicity activity with the double targeting. Methods: Initially 20 patients with refractory metastatic disease were treated with GAT administered at 1400 mg Q2W in combination with the glyco-optimized anti-EGFR antibody Tomuzotuximab (TOM) at 1200 mg Q2W. Due to the risk of infusion related reactions, three cycles of TOM were given before start of combined treatment with GAT. After this regimen was proven safe and no DLT was observed, 30 additional patients including colorectal cancer (CRC) already treated with anti-EGFR antibodies, non-small cell lung cancer (NSCLC), head and neck and breast cancers received TOM and GAT administered at the same doses, with GAT treatment starting already one week after the first dose of the anti-EGFR antibody. As allowed in the study expansion, Panitumumab (PAN) was used in place of TOM in 9 CRC patients at investigator’s choice. Results: By the time of the final analysis in January 2021, 52 patients were enrolled, and 50 received at least one dose of both GAT and anti-EGFR antibodies. Safety was overall good and results are reported in a separate abstract. Because of the difference in treatment schedule, activity results of the two parts of the study are summarized separately. There were 2 and 4 RECIST partial responses in the first and second part of the study, all in CRC patients. In the expansion phase, the median Progression Free Survival (PFS) of CRC patients who received TOM (10) and PAN (9) was 1.9 and 5.5 months, respectively. There were 2 responses in each subgroup and the duration of response was 3.8 and 7.2 months in patients receiving TOM and PAN, respectively. The PFS for NSCLC was 5.3 months and 2 heavily pretreated patients achieved a prolonged control of disease of 10.6 and 9.4 months. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 in serum. In the extension phase patients with baseline values above median appeared to have improved PFS and overall survival; this was not the case for patients of the first part of the study who received GAT only after 3 doses of TOM. Conclusions: Combination of TA-MUC1 and EGFR targeting antibody is safe and feasible. Interesting anti-tumor activity was observed in heavily pretreated CRC and NSCLC patients. Levels of soluble TA-MUC1 may have predictive value and potentially be a companion biomarker for further development of the combination Clinical trial information: NCT03360734.

Objective: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. Materials and methods: Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient's family history was considered as potentially BRCA-associated. Patients or disease characteristics were examined using the chi(2) test or Fisher's exact test for qualitative variables and the Student's t-test or Mann-Whitney test for continuous variables, as appropriate. Results: Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P = 0.01). The gBRCApv rate was 17.1% among patients <40 years old, 10.4% among patients 41-50 years old, 9.2% among patients 51-60 years old, 6.7% among patients aged 61-70 years, and 6.2% among patients >70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients <74 years old was 9%. Patients with/without a family history of potentially BRCA-associated tumors had 14%/6% mutations. Conclusion: Based on our findings of a gBRCApv incidence higher than expected in a real-life series of Italian patients with incident PDAC, we recommend screening all PDAC patients <74 years old, regardless of family history and stage, due to the therapeutic implications and cancer risk prevention in patients' relatives.

BACKGROUND:Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting.PATIENTS AND METHODS:gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed.RESULTS:A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS.CONCLUSIONS:Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.

Pancreatic Ductal Adenocarcinoma (PDAC) harboring germlineBRCA1-2 pathogenic variants (gBRCA1-2pv) is emerging as a distinct entity, benefitting from specific treatments (platinum agents, PARP-inhibitors). Information on second-line therapy (2LT) outcome in this setting is lacking.

The real world of clinical care of pancreatic ductal adenocarcinoma (PDAC) is poorly understood. The aim of the observational prospective study is to describe the therapeutic management for naïve patients (pts) with PDAC and evaluate the agreement with recommendations provided by the Italian Association of Medical Oncology (AIOM 2017). As secondary aims, to estimate Overall Survival (OS), Disease-Free Survival (DFS) and Progression-Free Survival (PFS) of pts. This is an observational, multicenter prospective, Italian study. Participating institutions were selected to represent different geographical and expertise areas (high-volume with >50 pts; medium-volume with 25-50 pts; low-volume with <25 pts treated /year). The treatment recommendation was related only to the physician's choice: the Study includes 3 different groups of treatment-naïve consenting pts with pathological diagnosis of PDAC: 1) pts receiving adjuvant therapy after resection; 2) pts receiving primary chemotherapy; 3) metastatic pts. Here we present the results of the accrual between November 2017 and October 2019, in order to get an appropriate evaluation of agreement with current Guidelines. 659 eligible pts were enrolled in 43 Italian centers: Nord 494 (75%), Centre 84 (13%), South 81 (12%); high-volume 431 (66%); medium-volume 121 (18%); low-volume 107 (16%). Home to hospital distance was ≤50 km for 88% of pts.Median age was 69.0 (range 35.6-89.1); 52% male; 93% ECOG PS 0-1; clinical stage: 8% I, 15% II, 25% III, and 52 % IV. Guidelines adherence was 74% in group 1; 97% in group 2; 98% in group 3. The most frequently administered regimens were: Group 1 (N=148): gemcitabine (G) 39%; nab-paclitaxel + G (AG) and FOLFIRINOX 21% each; group 2 (N=174) AG 57%; FOLFIRINOX 26%; G 13%; group 3 (N=337) AG 74%; G 16%; FOLFIRINOX 6%. A constant update of medical knowledge and a continuous revision of therapeutic guidelines are crucial to handover progress in real time in the clinical practice. Retrieving real-world data to verify guidelines adherence allows driving educational policies of scientific societies. The data of our study, whose enrollment is ongoing, show a very high rate of adherence with some attrition in the adjuvant setting.

Background: GAT (Gatipotuzumab) is a novel humanized monoclonal antibody, which recognizes the tumor-specific epitope of mucin-1 (TA-MUC1). TO (Tomuzotuximab) is a second-generation anti-EGFR antibody that specifically binds to EGFR. Both antibodies are glyco-engineered to potentiate antibody-dependent cellular cytotoxicity (ADCC). Preclinical evidence suggests a complex interaction between EGFR and cell surface expressed TA-MUC1 and shows a synergistic antibody dependent cell cytotoxicity activity with dual targeting of these molecules. The GATTO study initially assessed the tolerability, safety and preliminary activity of anti-TA-MUC1 and anti-EGFR combination in 20 patients with refractory solid tumors (ESMO GI 2019 abstract 848). Afterwards a study extension has been started in which a different anti-EGFR could be optionally used in place of TO.

To date, no information about the optimal duration of upfront chemotherapy in patients affected by pancreatic adenocarcinoma (PDAC) is available. We explored the role of chemotherapy holiday in patients who responded to nab-paclitaxel-gemcitabine (AG) based regimens. We retrospectively analyzed the outcome of 40 PDAC patients who had disease control (DC = partial response [PR] or stable disease [SD]) after 4-8 cycles of 1st-line AG-based chemotherapy (i.e. AG or PAXG = cisplatin, nab-paclitaxel, gemcitabine, capecitabine), allowing a chemotherapy holiday until progression, then retreated with AG/PAXG. Between 2015 and 2019, 40 chemo-naïve patients had DC with AG-based chemotherapy for stage IV (N=21; 17 AG, 4 PAXG) or stage II-III PDAC (N=19; 14 AG, 5 PAXG) at our Institution. Median age was 61 (28-75), 19 patients were males (47.5%) and 21 females (52.5%), ECOG performance status was 0-1 for all patients. Seventeen metastatic patients had PR (81%) and 4 had SD (19%). CA19-9 response was recorded in 18/20 assessable patients (90%). Median (m) PFS1 and OS1 were 10.3 and 23.2+ months (mo), respectively. Stage II-III patients had PR in 12 cases (63%) and SD in 7 (37%). CA19-9 response was recorded in 16/17 evaluable patients (94%). mPFS1 and mOS1 were 11.7 and 21.4+ mo respectively. Grade 3-4 side effects were neutropenia (57%), fatigue (15%), infections (12.5%), thrombocytopenia (10%) and anemia, nausea, peripheral neuropathy (2.5%). At time of PD, 34 patients were retreated for stage IV (A; 31 AG, 3 PAXG) and 6 for stage II-III (B, all AG). In group A, the median duration of chemotherapy holiday was 6.1 mo (3-25.7), 14 patients (41%) had PR and 12 (35%) had SD (DCR 76%). CA19-9 response was recorded in 22/32 evaluable patients (69%). mPFS2 and mOS2 was 5.3 and 12.1+ mo respectively. Patients with chemo holiday between 3 and 6 mo had a mPFS2 of 4.2 as opposed to 6.2 mo for patients with holiday lasting >6mo. Similarly, mOS2 was 10.3 versus 12.1 mo, respectively. At PD, 8 patients (36%) were still re-treated with AG yielding 2 PR, 4 SD (DC 75%) and mPFS3 of 5+ mo, with a chemo holiday period of 5.1 (2.6-8.9). After AG failure, further chemotherapy was administered to 19 patients (56%). In group B, the median duration of chemotherapy holiday was 7.4 mo (5.8-13.5), 1 patient (17%) had PR and 4 (67%) had SD (DC 84%). CA19-9 response was recorded in 4/5 evaluable patients. mPFS2 and mOS2 was 5.6 and 24 mo, respectively. Grade 3-4 neutropenia (50%), peripheral neuropathy (10%), anemia and thrombocytopenia (7.5%), fatigue, nausea and infection (5%) were reported. Re-treatment with the same schedule after a durable chemotherapy holiday seems to be a valuable option, reaching a clinically relevant DC rate and mPFS2, preserving a manageable safety profile, and allowing 2nd-line chemotherapy in a large number of patients. This strategy may provide a potential remarkable benefit for patient quality of life.

Introduction: We analyzed time to CA19-9 nadir during first-line chemotherapy in patients with metastatic, unresectable, and borderline resectable pancreatic ductal adenocarcinoma (PDAC) to investigate the relationship between biomarker response and duration of chemotherapy Methods: We analyzed data of PDAC patients with elevated CA19-9 baseline levels who received ≥4 months chemotherapy from the databases of prospective trials conducted at our Institution between April 1997 and May 2016. Patients were arbitrarily categorized based on time to CA19-9 nadir into 3 groups (A, B, C) for metastatic, and 3 groups (D, E, F) for non-metastatic disease. The time to nadir occurred during the first 3 months for group A and D, at month 4 for group B and E, and after month 4 for group C and F. Patients were also grouped based on chemotherapy regimen (gemcitabine, taxane-free, and taxane-containing regimens). Results: Altogether, 646 patients were considered. Among 407 metastatic patients, 346 (85%; 18 gemcitabine alone, 225 taxane-free, 103 taxane-including regimens) had elevated baseline CA19-9. Of those, 235 (68%) received chemotherapy for ≥ 4 months: 59% were males, 59% had Karnofsky performance status (KPS) 90-100%, median age was 61 years, median CA19-9 was 1066. Median survival was 8.6 months, 1y-OS 22%, 2y-OS 5%, for 59 group A. In group B (n = 80), mOS was 10.5 months, 1y-OS 40%, 2y-OS 6%. In group C (n = 96), mOS was 15.9 months, 1y-OS 72%, 2y-OS 23% (C vs A and C vs B: P < .0001). The likelihood to yield CA19-9 nadir at month 4 was 6% for gemcitabine; 26% for taxane-free regimen; and 20% for taxane-containing regimens. Nadir after month 4 was reported in 11% of gemcitabine-treated patients; 23% of those receiving a taxane-free regimen; and 42% of patients administered a taxane-containing regimen (P = .01). Among 239 non-metastatic patients, 28 (12%) were resected; 163 (77%; 9 gemcitabine alone, 92 taxane-free, 62 taxane-including regimens) had elevated baseline CA19-9 value. Of those, 119 (73%) received chemotherapy for ≥ 4 months: 55% were males, 65% had KPS 90-100%, median age was 63 years, median CA19-9 364. Group D included only 7 patients, who survived 7.7-22.0 months, 1-y OS was 71%, and 2-y OS 0%. mOS was 16.6 months in 55 group E patients who had 1y-OS 67% and 2y-OS 20%. In group F (N = 57), mOS was 18.6 months, 1y-OS 86%, 2y-OS 30% (P = 0.03). The likelihood to yield CA19-9 nadir at month 4 was 33% for gemcitabine; 35% for taxane-free regimens; and 32% for taxane-containing regimens. Nadir after month 4 was reported in any of gemcitabine-treated patients; 29% of those receiving a taxane-free regimen; and 48% of patients administered a taxane-containing regimen (P = .16). Conclusion: Fifty-one percent of patients with metastasis and 69% of patients with non-metastasis achieved CA19-9 nadir after ≥ 4 months of chemotherapy. Taxane-containing regimens obtained a CA19-9 nadir at ≥ 4 months more often. A later nadir appeared to be associated with a better outcome. CA19-9 modifications could drive treatment duration and better select patients who are candidates for surgery. A prolonged duration (>4 months) of induction treatment in candidates to surgery warrants prospective assessment.