First- and Second-Line Palliative Systemic Treatment Outcomes in a Real-World Metastatic Pancreatic Cancer Cohort

Background: Metastatic pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor survival rate, which can be improved by systemic treatment. Consensus on the most optimal first- and second-line palliative systemic treatment is lacking. The aim of this study was to describe the use of first- and second-line systemic treatment, overall survival (OS), and time to failure (TTF) of first- and second-line treatment in metastatic PDAC in a real-world setting. Patients and Methods: Patients with synchronous metastatic PDAC diagnosed between 2015 and 2018 who received systemic treatment were selected from the nationwide Netherlands Cancer Registry. OS and TTF were evaluated using Kaplan-Meier curves with log-rank test and multivariable Cox proportional hazard analyses. Results: The majority of 1,586 included patients received FOLFIRINOX (65%), followed by gemcitabine (18%), and gemcitabine + nab-paclitaxel (13%) in the first line. Median OS for first-line FOLFIRINOX, gemcitabine + nab-paclitaxel, and gemcitabine monotherapy was 6.6, 4.7, and 2.9 months, respectively. Compared to FOLFIRINOX, gemcitabine + nab-paclitaxel showed significantly inferior OS after adjustment for confounders (hazard ratio [HR], 1.20; 95% CI, 1.02–1.41), and gemcitabine monotherapy was independently associated with a shorter OS and TTF (HR, 1.98; 95% CI, 1.71–2.30 and HR, 2.31; 95% CI, 1.88–2.83, respectively). Of the 121 patients who received second-line systemic treatment, 33% received gemcitabine + nab-paclitaxel, followed by gemcitabine (31%) and FOLFIRINOX (10%). Conclusions: Based on population-based data in patients with metastatic PDAC, treatment predominantly consists of FOLFIRINOX in the first line and gemcitabine with or without nab-paclitaxel in the second line. FOLFIRINOX in the first line shows superior OS compared with gemcitabine with or without nab-paclitaxel.

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Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

Case Reports in Oncology ◽

10.1159/000504471 ◽

2020 ◽

Vol 13 (1) ◽

pp. 79-84

Author(s):

Dilara Akhoundova Sanoyan ◽

Cäcilia S. Reiner ◽

Panagiota Papageorgiou ◽

Alexander R. Siebenhüner

Keyword(s):

Systemic Treatment ◽

Sequential Treatment ◽

Phase Iii ◽

Ductal Adenocarcinoma ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Curative Surgery ◽

To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

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A nationwide population-based study comparing survival in unresectable advanced or synchronous metastatic esophageal and gastric adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.308 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 308-308

Author(s):

Marieke Pape ◽

Pauline A.J. Vissers ◽

David Bertwistle ◽

Laura McDonald ◽

Hanneke W.M. Van Laarhoven ◽

...

Keyword(s):

Systemic Treatment ◽

Rank Test ◽

Tumor Characteristics ◽

Line Treatment ◽

First Line ◽

Treatment Regimens ◽

Netherlands Cancer Registry ◽

Number Of Patients ◽

Significant Difference ◽

First Line Treatment

308 Background: Similarities between esophageal and gastric adenocarcinomas have been identified in terms of genomic characteristics. There is however no consensus on the combined or stratified inclusion of esophageal adenocarcinoma (EAC) within gastric cancer (GC) clinical trials. The aim of our study was to compare patient and tumor characteristics, first-line treatment regimens and overall survival (OS) of patients with EAC and GC. Methods: We selected patients with unresectable advanced and/or synchronous metastatic EAC (n = 1554) or GC (including junction tumors; n = 2095) diagnosed in the period 2015-2017 from the nationwide Netherlands Cancer Registry. Patients with a positive HER2 test result and/or receiving trastuzumab as a first-line treatment were excluded. Data on OS were analyzed using Kaplan-Meier curves with Log-Rank test. Results: The EAC patient population had significantly more male patients (83% vs 66%), lower median age (68 vs 71 years) and higher median BMI (25.4 vs 24.5). Significant differences in location of metastases were identified, with higher percentages in non-regional lymph nodes (48% vs 28%), liver (50% vs 35%), lung (21% vs 9%) and bone (19% vs 7%) and lower in peritoneum (5% vs 42%), in EAC versus GC patients respectively. EAC patients more often received any type (supportive or active systemic) of treatment (76% vs 60%). Median OS was longer in EAC than GC patients (EAC: 4.8 vs GC: 4.1 months; p < 0.01). The percentages of patients receiving first-line systemic treatment were equal in both groups (43%). The number of patients receiving CapOx or FOLFOX was not significantly different (43% vs 47%). Carboplatin+paclitaxel was more frequently given in EAC versus GC (34% vs 3%), while EOX or ECC was given less frequently (12% vs 30%). No significant difference was observed in median OS between EAC and GC patients receiving first-line active systemic treatment (8.0 vs 7.6 months; p = 0.28). Conclusions: Patient characteristics, tumor characteristics, treatment regimens and OS differ between EAC and GC patients. Despite these differences, in patients receiving first-line active systemic treatment no significant differences in OS were found.

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Real-world utilization and safety of ipilimumab plus nivolumab (I+N) in metastatic renal cell carcinoma (mRCC) patients: Results from the Canadian Kidney Cancer Information System (CKCis).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.633 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 633-633

Author(s):

Myuran Thana ◽

Naveen S. Basappa ◽

Sunita Ghosh ◽

Christian K. Kollmannsberger ◽

Daniel Yick Chin Heng ◽

...

Keyword(s):

Clinical Trial ◽

Real World ◽

Single Agent ◽

Cancer Information ◽

Time To Failure ◽

Line Treatment ◽

Second Line ◽

First Line ◽

To Receive

633 Background: I+N is now standard of care for first line treatment of intermediate/poor risk mRCC patients (pts). Real world data is vital to understand drug usage, toxicity and outcomes in non-trial pts. This project describes the amount and tolerability of treatment delivered including discontinuation rates, reasons for discontinuation and outcomes from the CKCis database. Methods: Pts in CKCis, a prospective Canadian database from 15 academic centers, who received first line I+N were included. The number of doses of I+N, number of pts who received single-agent nivolumab (N) and duration of single agent N were determined. Reasons for treatment discontinuation, including the rate, type, and grade of toxicities were identified. Efficacy outcomes included time to failure (TTF – time to progression, death, or second line therapy), overall response rate (ORR) and overall survival (OS). Results: The cohort consists of 182 pts. Median age was 63 yrs, 71% had clear cell histology, 11% were on a clinical trial, the IMDC risk distribution was 5% good, 63% intermediate, 32% poor. Median follow up was 8.8 m. All 4 I+N doses were received by 30% of pts of which 78% went on to receive single-agent N. Less than 4 doses of I+N were received by 70% of pts of which 28% went on to receive single-agent N. The median time on single agent N was 5.7 m. In the entire cohort, 21% of patients discontinued therapy due to toxicity. The most common toxicity events were colitis (56% of all events), pneumonitis (19%), and hepatitis (8%). There were no toxicity-related deaths. Median OS has not been reached (22 events to date). Median TTF was 12.4 m. ORR was 32% (5% complete responses). 26% of pts received second line treatment, the most common being sunitinib in 79%. Conclusions: In this real world cohort, the majority of mRCC pts did not receive all 4 doses of I+N, contrasting with clinical trial reporting, yet many of these pts went on to receive single agent N. Discontinuation rates due to toxicity were similar to those reported in CheckMate 214. Further follow up is ongoing and efficacy outcomes analyzed on the basis of treatment quantity/duration will be presented.

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Examining progression-free survival in first- and second-line treatment for BRAF-mutant metastatic colorectal cancer (CRC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.728 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 728-728

Author(s):

Belinda Lee ◽

Angelyn Anton ◽

Margaret Lee ◽

Rachel Wong ◽

Phillip Parente ◽

...

Keyword(s):

Colorectal Cancer ◽

Treatment Strategies ◽

Progression Free Survival ◽

Rank Test ◽

Second Line ◽

First Line ◽

Mutation Status ◽

Kaplan Meier ◽

The Impact ◽

Line Chemotherapy

728 Background: BRAF mutated (BRAFm) CRC represents ~10% of all CRC and is associated with significantly poorer prognosis. However, responses to chemotherapy do still occur. Some data suggest that the poor prognosis associated with BRAFm CRC is dominated by substantially poorer second line PFS (PFS2), whereas first line PFS (PFS1) was similar for both BRAFm and BRAF wildtype (BRAFwt) CRC. Using a large multicenter dataset, our study aimed to examine PFS1 and PFS2 in BRAFm versus BRAFwt CRC. Methods: Prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) database was interrogated. PFS was calculated and compared in patients with BRAFm versus BRAFwt CRC. Median survival was determined by the Kaplan-Meier method and compared using the log rank test. Results: TRACC identified 523 CRC patients with known BRAF mutation status, who received first-line chemotherapy: 53 (10%) were BRAFm, while 470 (90%) were BRAFwt. At the time of data analysis, only 231 (44%) CRC patients had received second-line chemotherapy, of which 21 (9%) were BRAFm and 210 (91%) were BRAFwt. PFS1 analyses demonstrated significantly poorer survival in the BRAFm population (Median 7.8mo versus 11.5mo, HR 1.72, p = 0.0026). PFS2 analyses revealed similar findings for the BRAFm population, albeit non-significant due to smaller numbers (Median 5.5mo versus 7.7mo, HR1.26, p = 0.44). Conclusions: Our study demonstrated that BRAFm CRC was associated with poorer PFS in both first- and second-line settings. Additional analyses will be performed to examine the impact of different treatment strategies and other clinicopathological features.

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The role of targeted therapy (TKI) in the treatment of advanced hepatocellular carcinoma (aHCC) in the era of immunotherapy: Real-world data using AI analytics from an academic medical center.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16623 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16623-e16623

Author(s):

Rachel Su Jen Wong ◽

Jiaxuan Wu ◽

Alisha Joan Leen ◽

Glenn Jin Chong Tey ◽

Yugarajah Asokumaran ◽

...

Keyword(s):

Clinical Outcomes ◽

Real World ◽

Systemic Therapy ◽

Medical Center ◽

Academic Medical Center ◽

Rank Test ◽

Advanced Hepatocellular Carcinoma ◽

Second Line ◽

First Line ◽

Real World Data

e16623 Background: The management of aHCC has evolved dramatically in recent years, with new agents like immunotherapy receiving regulatory approval. As we begin incorporating these drugs into routine clinical practice, data on real-world sequencing of therapies and clinical outcomes are needed. Methods: We utilised the DISCOVERYAI platform, a virtual machine containing de-identified patient electronic health records to review HCC patients treated at the National University Health System, Singapore from January 2015 to December 2019. We then identified those who received systemic therapy and correlated their clinical outcomes. Results: In total, 395 HCC patients were identified; 75 received surgery, 174 received loco-regional therapy and 102 referred for consideration of systemic therapy. Of those considered for systemic therapy, median age was 65 years (range 23-87); 88% male (n = 90); hepatitis B/hepatitis C/non-hepatitis, 41(40.2%)/ 10(9.8%)/ 51(50.0%). 75.5% (n = 77) of them received systemic therapy with a TKI and/or immunotherapy. 39% (n = 30) of these received second-line treatment. Child-Pugh score at start of treatment was A5/A6/B7/B8, 38(49.3%)/ 32(41.6%)/ 5(6.5%)/ 2(2.6%) respectively. In the first-line, 66% (n = 51) received TKI and 34% (n = 26) received immunotherapy. Amongst those treated with first-line TKI, 45% (n = 23) received second-line therapy; 65% (n = 15) immunotherapy, 35% (n = 8) another TKI. Of those treated with first-line immunotherapy, 27% (n = 7) received second-line TKI. At a median follow-up of 35 months, first-line median progression-free survival (mPFS) for TKI vs immunotherapy was 3.7 vs 3.1 months (HR 0.73; 95% CI, 0.40-1.33; p = 0.31). mPFS for second-line immunotherapy vs TKI was 4.0 vs 2.9 months (HR 0.43; 95% CI, 0.19-0.96; p = 0.04). When comparing sequencing of therapies, the combined first and second mPFS for TKI-immunotherapy/TKI-TKI/immunotherapy-TKI is 9.5/7.6/7.6 months respectively (log-rank test, p = 0.71). Those patients that received both immunotherapy and TKI had significantly higher overall survival (OS) compared to those receiving only immunotherapy or only TKI or none (mOS NR vs 10.1 vs 13.2 vs 4.7 months; p < 0.001). Conclusions: TKI remains an important pillar of treatment in aHCC in the era of immunotherapy. While immunotherapy provides long durable responses and benefit in a minority of patients, the majority appear to benefit from TKI. Biomarker studies are needed to discern treatment algorithms for aHCC.

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Rate of conversion from unresectable to resectable metastatic colorectal cancer (mCRC) in real-world patients (RWP) treated with FOLFIXIRI ± bevacizumab: A population-based retrospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.21 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 21-21

Author(s):

Tayyaba Bhatti ◽

Michael Moser ◽

Jon Tan ◽

Adnan Zaidi ◽

Duc Le ◽

...

Keyword(s):

Real World ◽

Positive Response ◽

Performance Status ◽

Tumor Resection ◽

Progression Free Survival ◽

Population Based ◽

Response To Therapy ◽

Response To Treatment ◽

Rank Test ◽

Kaplan Meier

21 Background: Recent evidence from randomized trials suggests that FOLFOXIRI (5FU, oxaliplatin, and irinotecan) ± bevacizumab is associated with higher response rates with a potential for conversion of unresectable to resectable disease in mCRC. Yet limited evidence is available about efficacy and safety of this regimen in RWP with mCRC. The current study aims to evaluate conversion rate and safety of FOLFOXIRI ± bevacizumab in RWP with unresectable mCRC. Methods: Each year about 175 patients are diagnosed with mCRC in Saskatchewan. Patients who were diagnosed with unresectable mCRC between Jan 2015 to Dec 2018 and received FOLFOXIRI ±bevacizumab were assessed. Kaplan Meier survival methods and log rank test were performed. Logistic regression analysis was performed to assess factors correlate with conversion. Results: 28 eligible patients with median age of 51 yrs (IQR:39-60) and M:F of 11:16 were identified. 42% patients had a comorbid illness, and 43% had WHO performance status of 0. 39% had rectal cancer, 46% had extrahepatic disease and 46% had bilobar liver metastases. 58% patients had a positive response to therapy, 60% had grade 3/4 toxicity & 32% required hospital admission. No treatment-related mortality was noted. 54% patients underwent metastasectomy (liver 73%, peritoneum and or ovaries 20%, lung 6%). 68% had primary tumor resection, 29% received rectal radiation, 21% had ablation and 18% had second surgery for recurrence. At 4 years 50% patients are alive. Median progression free survival of patients who underwent surgery is 18 (95%CI:11.3-24.7) vs. 11 months (4-18.1) without surgery (P = 0.28). Median overall survival of patients with surgery is 33 (17.5-48.5) vs. 16 months (8.3-23.7) without surgery (P = 0.03). Positive response to treatment is correlated with conversion (odd ratio 21.7, p = 0.002). Conclusions: In the real world setting younger patients with good performance status received FOLFIRINOX ± bevacizumab. Despite high rates of toxicity, more than half of patients were able to undergo surgery. A positive response to treatment significantly correlates with metastasectomy.

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Serial cell-free DNA (cfDNA) sampling in advanced pancreatic ductal adenocarcinoma (PDAC) patients may predict therapeutic outcome.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.423 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 423-423

Author(s):

Gehan Botrus ◽

Yu Fu ◽

Mohamad Bassam Sonbol ◽

Leylah Drusbosky ◽

Daniel H. Ahn ◽

...

Keyword(s):

Overall Survival ◽

Progression Free Survival ◽

Ductal Adenocarcinoma ◽

Rank Test ◽

First Line ◽

Free Survival ◽

Probability Of Survival ◽

First Line Therapy ◽

Kaplan Meier ◽

Next Generation Sequencing Ngs

423 Background: Advanced PDAC remains a deadly disease with a 5-year survival rate of less than 10%. cfDNA - based next generation sequencing (NGS) may identify actionable alterations in patients with PDAC. In this study, we aim to determine the feasibility of utilizing serial cfDNA NGS testing and its potential relevance in predicting therapeutics outcomes. Methods: A total of 23 PDAC patients with PDAC cfDNA isolated from plasma collected at diagnosis and upon disease progression to first line SOC therapy and were analyzed on a 73-74 gene NGS panel (Guardant Health). Changes in molecular profiles from baseline to progression were analyzed for overall survival, progression free survival (PFS), and treatment response. PFS and OS were analyzed using the Kaplan-Meier method and the log-rank test was used to compare the survival of different groups of patients. All p-values were two-sided. Analyses were performed using R (version 3.5.1, R Foundation, Vienna, Austria). Results: In this retrospective study, the 1-year probability of survival was 71% (median 473 days) and the 1-year PFS was 14% (median 212 days). TP53 and KRAS were the most frequently mutated genes identified in baseline samples, with 78% prevalence for each. Patients with clearance of TP53 17% (3/18) patients and/or KRAS 33% (6/18) patients clones after first line therapy significantly increases PFS (p=0.0056 and p=0.037, with HR of 0.087 and 0.32, respectively). However, appearance of TP53 or KRAS alterations upon progression does not significantly affect overall survival or PFS. Conclusions: The preliminary results from this study suggest that cfDNA clearance of TP53 and/or KRAS alterations may predict for improved PFS in PDAC. Confirmation of these findings in larger studies is warranted.

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The association between real-world CA19-9 level monitoring patterns and with clinical outcomes among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in the second- and third-line of therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16251 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16251-e16251

Author(s):

Ben George ◽

Aleksander Chudnovsky ◽

Paul Cockrum ◽

Neil Lamarre ◽

Matthew Kent ◽

...

Keyword(s):

Clinical Outcomes ◽

Real World ◽

Treatment Initiation ◽

Diagnostic Testing ◽

Population Based ◽

Ductal Adenocarcinoma ◽

Rank Test ◽

Baseline Serum ◽

Third Line ◽

The Impact

e16251 Background: Pancreatic cancer has an aggressive disease course, mandating close clinical monitoring while on treatment. Evaluation of treatment response in patients with mPDAC necessitates scheduled clinical and radiographic assessments along with monitoring serum CA 19-9 levels. We investigated the impact of serum CA 19-9 monitoring and its association with clinical outcomes in patients with mPDAC who received second- (2L) and third line (3L) in a population-based setting. Methods: Data were extracted from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database for patients diagnosed with mPDAC and subsequently treated in the 2L or 3L setting between January 1, 2014 and June 30, 2020. Serum CA 19-9 levels at baseline were extracted – defined as the values obtained ≤ 60 days of treatment initiation and during treatment. CA 19-9 levels > 40 IU/mL were considered elevated. Survival analysis was performed using Kaplan-Meier methods. Categorical measures were compared with a chi-square test and survival outcomes with a log-rank test. Results: There were 2,402 patients who received 2L and 790 patients who received 3L treatment included in the study. Among the 2L cohort, median age at treatment initiation was 67 years (IQR: 60 – 73), 54% were male, 57% had an ECOG score of 0-1, and 82% had a baseline serum CA 19-9 level available. Among the 3L cohort, median age at treatment initiation was 67 years (IQR: 60 – 73), 53% were male, 58% had an ECOG score of 0-1, and 84% had a baseline CA 19-9 level available. Most patients in the 2L and 3L cohorts had an elevated CA 19-9 at baseline, 85.2% and 82.0%, respectively. Among the 2L and 3L cohorts, 38.5% and 31.9% had CA 19-9 levels decrease/remain stable during treatment and 27.6% and 31.4% had levels increase during treatment, respectively. Patients with normal baseline CA 19-9 experienced longer survival than patients with elevated levels [2L: 7.2 months (95% CI: 6.1 – 9.2) vs 5.2 months (4.9 – 5.6), p < 0.001; 3L: 6.1 months (5.4 – 9.1) vs 3.9 months (3.4 – 4.3), p < 0.001]. Similarly, patients with decreasing/stable CA 19-9 during treatment had longer survival than patients who had their CA 19-9 levels increase [2L: 8.2 months (7.7 – 8.5) vs 4.3 months (4.1 – 4.7), p < 0.001; 3L: 7.5 months (6.6 – 9.2) vs 3.7 months (3.4 – 4.3), p < 0.001]. Conclusions: In this large, contemporary, real-world study of patients with mPDAC, CA 19-9 levels at treatment initiation had a prognostic value across later lines of therapy. Routine serial monitoring of CA 19-9 levels during treatment, in addition to clinical and radiographic assessment, may help with timely additional diagnostic testing and treatment intervention. Further validation studies are needed to understand the generalizability of these results.

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Real-world study of treatment patterns and outcomes among patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in Europe.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.391 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 391-391

Author(s):

Julien Taieb ◽

Pascal Hammel ◽

Michele Reni ◽

Daniel H. Palmer ◽

John A. Bridgewater ◽

...

Keyword(s):

Metastatic Disease ◽

Real World ◽

Performance Status ◽

Real Life ◽

Treatment Patterns ◽

Ductal Adenocarcinoma ◽

Second Line ◽

First Line ◽

Life Study ◽

Line Therapy

391 Background: Few data are available regarding real-world treatment patterns and outcomes for metastatic PDAC (mPDAC) in Europe. Methods: This retrospective, observational, chart-review study involved medical oncologists and gastroenterologists from France, Germany, Italy, Spain, and the UK. Physicians completed online patient (pt) reports for 20 consecutive pts diagnosed with PDAC between 01 and 10/2016. Here, the analysis is focused on treated pts diagnosed with mPDAC. Reports provided information on general disease and pt characteristics, diagnosis, and treatment of metastatic disease. Outcomes included median PFS and OS according to each line of metastatic therapy. In addition, how baseline performance status (PS) and treatment sequence affected OS and PFS were assessed. Results: 304 physicians (France [n=62], Germany [n=60], Italy [n=63], Spain [n=66], UK [n=53]) participated and enrolled 6,000 pts with PAC, of whom 3827 had mPDAC. Of the 3827, 3432 were treated for their metastatic disease. The most common first-line therapies were modified FOLFIRINOX (28.4%), gemcitabine + nab-paclitaxel (28.0%), and gemcitabine monotherapy (23.0%), while the most common second-line therapies were gemcitabine monotherapy (25.0%), 5-FU + oxaliplatin (21.8%), and gemcitabine + nab-paclitaxel (16.7%). The longest median PFS and OS were obtained when using mFOLFIRINOX as first-line therapy, with gemcitabine-based combinations as second-line therapy. However, pt characteristics were more favorable with FOLFIRINOX compared with the other regimens used in first line. The most common treatment in first line for patients with a worse baseline PS (PS >1) was gemcitabine monotherapy (571 patients [46%]); in addition, having a worse baseline PS was predictive of shorter survival in second line. The most common reason for discontinuation of either line was disease progression. The study showed that the choice of first- and second-line treatment among European physicians is in accordance with current ESMO guidelines; in contrast, the choice of subsequent line was more heterogeneous, according to local practices. Additional data concerning first and second line OS and PFS per treatment regimen will be presented at the meeting. Conclusions: This large real-life study highlights a clear picture of treatment patterns in European real-world clinical practice and outcomes for metastatic PDAC, which may help in more effectively managing such patients in the future. Further univariate and multivariate analysis will complete this first description.

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Gender Differences in Treatment Allocation and Survival of Advanced Gastroesophageal Cancer: a Population-Based Study

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djab075 ◽

2021 ◽

Author(s):

Willemieke P M Dijksterhuis ◽

Marianne C Kalff ◽

Anna D Wagner ◽

Rob H A Verhoeven ◽

Valery E P P Lemmens ◽

...

Keyword(s):

Gender Differences ◽

Systemic Treatment ◽

Statistical Tests ◽

Tumor Biology ◽

Rank Test ◽

Lower Probability ◽

Gastroesophageal Cancer ◽

Treatment Allocation ◽

Netherlands Cancer Registry ◽

Treatment Administration

Abstract Background Biological sex and gender have been reported to impact incidence and overall survival (OS) of curatively treated gastroesophageal cancer. The aim of this study was to compare palliative treatment allocation and OS between women and men with advanced gastroesophageal cancer. Methods Patients with an unresectable (cT4b) or metastatic (cM1) esophageal (including cardia) adenocarcinoma (EAC) or squamous cell carcinoma (ESCC), or gastric adenocarcinoma (GAC) diagnosed in 2015-2018 were identified in the Netherlands Cancer Registry. Treatment allocation was compared using chi-squared tests and multivariable logistic regression analyses, and OS using the Kaplan-Meier method with log-rank test and Cox proportional hazard analysis. All statistical tests were 2-sided. Results Of patients with EAC (n = 3,077), ESCC (n = 794) and GAC (n = 1,836), 18.0%, 39.4% and 39.1% were women, respectively. Women received less often systemic treatment compared to men in EAC (42.7% vs. 47.4%, P = 0.045) and GAC (33.8% vs. 38.8%, P = 0.03), but not in ESCC (33.2% vs. 39.5%, P = 0.07). Women had a lower probability of receiving systemic treatment in GAC in multivariable analyses (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.62-1.00), but not in EAC (OR = 0.86, 95%CI = 0.69-1.06) and ESCC (OR = 0.81, 95%CI = 0.57-1.14). Median OS was lower in women with EAC (4.4 vs. 5.2 months, P = 0.04), but did not differ after adjustment for patient and tumor characteristics and systemic treatment administration. Conclusion We observed statistically significant and clinically relevant gender differences in systemic treatment administration and OS in advanced gastroesophageal cancer. Causes of these disparities may be sex-based, i.e. related to tumor biology, as well as gender-based, e.g. related to differences in treatment choices.

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