Association of losartan use with outcomes in metastatic pancreatic cancer patients treated with chemotherapy.

e16738 Background: A phase II trial has shown improved efficacy of neoadjuvant therapy when combined with losartan (by remodeling desmoplasia) in locally advanced pancreatic ductal adenocarcinoma (PDA). However, role of losartan is unknown in metastatic PDA. We examined the relationship between the use of the angiotensin II receptor antagonist, losartan, at time of diagnosis with clinical outcomes in metastatic PDA pts that received chemo. Methods: We retrospectively evaluated 114 metastatic PDA pts treated at our center between Jan 2000 and Nov 2019. We compared OS, PFS, objective response rate (ORR), and disease control rate (DCR) between pts using losartan at time of cancer diagnosis and a control group of pts not on losartan. A subanalysis was performed based on losartan dose: 100mg dose versus control pts. and based on chemo: FOLFIRINOX or gemcitabine+abraxane. Results: Table shows baseline demographics. No significant difference was found in OS [p = 0.455] or PFS [p = 0.919] in pts on losartan (median 274d, 83d) vs control (median 279d, 111d) [p = 0.466]. No significant difference was found in ORR [p = 0.621] or in DCR [p = 0.497]. No significant difference was found in OS [p = 0.771] or PFS [p = 0.064] in losartan pts (median 347d, 350d) vs control (median 333d, 101d) treated with FOLFIRINOX. No significant difference was found in OS [p = 0.916] or PFS [p = 0.341] in losartan (median 312d, 69d) vs control (median 221d, 136d) [p = 0.916] treated with gemcitabine+abraxane. No significant difference was found in OS [p = 0.727] or PFS [p = 0.790] in 100mg losartan pts (median 261d, 84d) vs control (median 279d, 111d). Conclusions: Pts on losartan at time of diagnosis had no significant difference in OS, PFS, ORR, DCR than control pts. However, a subanalysis of pts treated with FOLFIRINOX revealed a longer PFS with losartan than control but did not meet statistical significance, likely due to small sample size. To confirm if the benefit of losartan + FOLFIRINOX seen in neoadjuvant setting for locally advanced cancer also applies to metastatic cancer, our findings need to be validated in a larger cohort. [Table: see text]

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External Beam Therapy in a Four-Field Box Technique with Paclitaxel versus a Two-Field Technique with Cisplatin in Locally Advanced Carcinoma Cervix: A Phase II Monocentric Trial

ISRN Oncology ◽

10.5402/2012/390193 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6

Author(s):

Vijayakumar Narayanan ◽

Bibek Bista ◽

Samir Sharma

Keyword(s):

Phase Ii ◽

Treatment Time ◽

Small Sample Size ◽

Objective Response ◽

Locally Advanced ◽

Standard Of Care ◽

Small Sample ◽

External Beam ◽

Overall Treatment Time ◽

Significant Difference

Introduction. External beam pelvic radiotherapy with cisplatin and brachytherapy is the standard of care for patients with advanced cervical malignancy. This study was aimed at evaluating the toxicity of a two-field radiotherapy with cisplatin and brachytherapy compared to a four-field box technique with paclitaxel and brachytherapy for stages IIB/IIIB cervical cancer. The differences in response to the overall treatment were also examined. Methods. 35 patients were enrolled in this phase II prospective randomized trial conducted from February 2006 to February 2007. In arm I, up to 40 Gy in 20 fractions followed by 10 Gy in 5 fractions in split field with cisplatin 40 mg/M2 and, in arm II, 50 Gy in 25 fractions with paclitaxel 50 mg/M2 were given. Results. Toxicity in genitourinary, lower gastrointestinal, and hematological tissues was significantly higher in arm I. The duration of concurrent chemoradiotherapy in either arm was similar. The overall treatment time was less in arm II. No statistically significant difference in the objective response was observed between arms. Conclusion. Two-field radiotherapy with cisplatin is a tolerable regime but more toxic than four-field box radiotherapy with paclitaxel. The major setbacks are that a radiotherapy technique as well as chemotherapy is different; hence, toxicity and outcome of treatment should be viewed as a collective response of the whole treatment regimen and the small sample size.

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Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

Urologia Journal ◽

10.1177/03915603211035191 ◽

2021 ◽

pp. 039156032110351

Author(s):

Alessandro Uleri ◽

Rodolfo Hurle ◽

Roberto Contieri ◽

Pietro Diana ◽

Nicolòmaria Buffi ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Advanced Disease ◽

Independent Predictor ◽

Small Sample Size ◽

Statistical Significance ◽

Locally Advanced ◽

Small Sample ◽

Locally Advanced Disease ◽

Increased Risk

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

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Coronavirus disease-2019 in cancer patients. A report of the first 25 cancer patients in a western country (Italy)

Future Oncology ◽

10.2217/fon-2020-0369 ◽

2020 ◽

Vol 16 (20) ◽

pp. 1425-1432 ◽

Cited By ~ 22

Author(s):

Elisa Maria Stroppa ◽

Ilaria Toscani ◽

Chiara Citterio ◽

Elisa Anselmi ◽

Elena Zaffignani ◽

...

Keyword(s):

Sample Size ◽

Antiviral Therapy ◽

Cancer Patients ◽

General Hospital ◽

Small Sample Size ◽

Statistical Significance ◽

Western Country ◽

Small Sample ◽

Control Group ◽

Worse Prognosis

Background: We describe cancer patients with coronavirus disease-2019 (COVID-19) infection treated at the Piacenza’s general hospital (north Italy). Materials & methods: 25 cancer patients infected by COVID-19 admitted at the Piacenza’s general hospital from 21 February to 18 March 2020. Outcome from the infection were compared with infected noncancer patients. Results: 20 patients (80%) were treated with antiviral therapy and hydroxychloroquine and five (20%) received hydroxychloroquine alone. Nine (36%) patients died, while 16 (64%) overcome the infection. In the control group the mortality was 16.13% and the overcome from infection was 83.87%. Conclusion: Mortality for COVID-19 was greater in cancer patients when compared with noncancer patients, worse prognosis for older age, women and patients treated with hydroxychloroquine alone. However, the comparisons did not reach statistical significance in most cases. This could be due to the small sample size that is the main limitation of the study.

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Acupuncture for Chronic Pain-Related Insomnia: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/5381028 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Fushui Liu ◽

Jianyu You ◽

Qi Li ◽

Ting Fang ◽

Mei Chen ◽

...

Keyword(s):

Chronic Pain ◽

Sample Size ◽

Small Sample Size ◽

Meta Analysis ◽

Sham Acupuncture ◽

Small Sample ◽

Control Group ◽

Large Sample Size ◽

Cure Rate ◽

Significant Difference

Objectives. Acupuncture has been widely used to relieve chronic pain-related insomnia (CPRI). However, the efficacy of acupuncture for CPRI is uncertain. The purpose of this study was to evaluate the efficacy of acupuncture for CPRI. Methods. Seven electronic databases were searched from inception to December 2018. Randomized controlled trials (RCTs) were included if acupuncture was compared to sham acupuncture or conventional drug therapies for treating CPRI. Two reviewers screened each study and extracted data independently. Statistical analyses were conducted by RevMan 5.3 software. Results. A total of nine studies involving 944 patients were enrolled. The pooled analysis indicated that acupuncture treatment was significantly better than control group in improving effective rate (OR = 8.09, 95%CI = [4.75, 13.79], P < 0.00001) and cure rate (OR = 3.17, 95%CI = [2.35, 4.29], P < 0.00001), but subgroup analysis showed that there was no statistically significant difference between acupuncture and sham acupuncture in improving cure rate (OR =10.36, 95% CI [0.53, 201.45], P=0.12) based on one included study. In addition, meta-analysis demonstrated that acupuncture group was superior to control group in debasing PSQI score (MD = -2.65, 95%CI = [-4.00, -1.30], P = 0.0001) and VAS score (MD = -1.44, 95%CI = [-1.58, -1.29], P < 0.00001). And there was no significant difference in adverse events (OR =1.73, 95%CI = [0.92, 3.25], P =0.09) between the two groups. Conclusions. Acupuncture therapy is an effective and safe treatment for CPRI, and this treatment can be recommended for the management of patients with CPRI. Due to the low quality and small sample size of the included studies, more rigorously designed RCTs with high quality and large sample size are recommended in future.

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ABCA3 Expression Predicts Response to Gemtuzumab Ozogamicin in AML

Blood ◽

10.1182/blood.v128.22.3946.3946 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3946-3946 ◽

Cited By ~ 1

Author(s):

Antony Ceraulo ◽

Aminetou Mint-Mohamed ◽

Delphine Maucort-Boulch ◽

Etienne Paubelle ◽

Xavier Thomas ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Relapse Rate ◽

Small Sample Size ◽

Univariate Analysis ◽

Gemtuzumab Ozogamicin ◽

Small Sample ◽

Control Group ◽

Prognostic Impact ◽

Significant Difference

Abstract Background. The ATP binding cassette transporter 3 (ABCA3) has been recently found to induce a significant reduction in cytotoxicity following exposure to anthracyclines, mitoxantrone, etoposide, Ara-C, vincristine, and rituximab. ABCA3 acts through the modulation of multivesicular bodies (MVB) and contributes to drug sequestration in late endosomal organelles, i.e. MVB and lysosomes. Studies having investigated the prognostic impact of ABCA3 expression in AML have yielded conflicting results as ABCA3 expression has both been reported to exert unfavorable or neutral effects on patient outcomes. In addition, the small sample size of these studies precluded the use of multivariate analyses. Methods. Our goal was to investigate the prognostic impact of ABCA3 expression in adult patients with AML treated with IC with or without gemtuzumab ozogamicin (GO). To this end we investigated the relationship between ABCA3 expression and EFS in a representative series of 221 AML homogeneously treated in the ALFA-0701 trial. qRTPCR amplification of conserved ABCA3 mRNA sequences, as identified with FasterDB database, was performed with GUS and ABL as reference genes. Primer sets were complementary to conserved ABCA3 exons 6-7 and exon 19-20 junctions. Patients were given a 3+7 induction course without (control group, n=110) or with fractionated intravenous GO (n=111) (Castaigne S, Lancet 2012; 379:1508-1516). Results. Among the 278 randomized patients, 221 had available bone-marrow diagnostic samples with high-quality RNA. The same benefits associated with GO were observed in the 221 patients from the present study as in the entire trial population. Overall, median age, CR rate, relapse rate, median follow-up, 3-years EFS were 62.1 years, 76.5%, 66%, 47.45 months, 28±3%, respectively. There was no significant difference in the level of ABCA3 expression between responders and non-responders. In the 169 responders, ABCA3 expression at diagnosis was more than 3-fold higher in the 111 remitters who subsequently relapsed than in the 58 patients who remained in persistent CR (p=0.033). The level of ABCA3 expression was significantly lower in ELN favorable group than in intermediate and adverse risk AML (p= 0.004) and negatively correlated with CD33 expression (R=-0.272, p<10-4). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±3 vs 45±7 % p=0.002). Multivariate analysis identified age, treatment arm, and ELN risk group as independent prognostic factors for EFS. In the control group, there was no significant association between ABCA3 expression and CR rate, relapse rate, and EFS. In the 111 patients within the GO arm, there was no significant difference in the level of ABCA3 expression between responders and non-responder whereas in the 89 responders, ABCA3 expression at diagnosis was more than 7-fold higher in the 53 remitters who subsequently relapsed than in the 36 patients who remained in persistent CR (p=0.006). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±5 vs 64±9 % p=0.0002). Multivariate analysis identified ABCA3 expression, cytogenetics, CD33 expression, and ECOG as independent prognostic factors for EFS (Figure 1). Conclusion. WhileABCB1 has been previously found to attenuate GO-induced cytotoxicity in AML cells (Walter RB, Blood 2003; 102:1466-1473), present results indicate that higher ABCA3 expression independently predicts poor outcome in AML patients treated with fractionated GO and intensive chemotherapy (IC). GO is an anti-CD33 antibody carrying a toxic calicheamicin derivative that, after hydrolytic release within lysosomal vesicles, induces DNA strand breaks, apoptosis, and cell death. Whether the clinical effect of ABCA3 expression relies on the modulation of CD33 internalization, calicheamicin release or combination thereof is under investigation. Finally our results encourage inhibiting ABCA3, such as with indomethacin, in order to overcome drug resistance in AML treated with GO-IC. Figure 1 Figure 1. Disclosures Thomas: Pfizer: Consultancy.

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A phase Ib dose escalation, safety, and tolerability study of sonidegib in combination with gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.371 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 371-371 ◽

Cited By ~ 4

Author(s):

Teresa Macarulla ◽

Josep Tabernero ◽

Daniel H. Palmer ◽

Sunil Sharma ◽

Kenneth H. Yu ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Dose Escalation ◽

Standard Dose ◽

Small Sample Size ◽

Objective Response ◽

Locally Advanced ◽

Small Sample ◽

Moderate Activity ◽

Current Standard ◽

Grade 3

371 Background: Sonidegib (LDE225) is a potent, selective, and orally bioavailable inhibitor of smoothened receptor that demonstrated preclinical activity in combination with gemcitabine (GEM). Here, we present data from a phase 1b trial of sonidegib in combination with GEM in patients (pts) with pancreatic adenocarcinoma (PA). Methods: Pts with histologically or cytologically confirmed, locally advanced, or metastatic PA who had not been treated previously or had progressed despite prior chemotherapy (other than GEM) were included in the study. Dose escalation started with sonidegib 400 mg, once a day, in combination with GEM 1000 mg/m2 IV infusion on days 1, 8, and 15 of a 28-day cycle. Results: A total of 18 pts were enrolled (9 pts each the in dose escalation and dose expansion phases). Pts discontinued the study because of disease progression (n = 11, 61.1%), consent withdrawal (n = 3, 16.7%), administrative problems (n = 3, 16.7%), and grade 3 or 4 blood creatine kinase (CK) elevation (n = 1, 5.6%). Three of 9 pts in dose escalation phase experienced dose-limiting toxicities during the first 8 weeks including grade 3 mucositis (n = 1), grade 3 CK elevation (n = 1), and grade 3 aspartate aminotransferase elevation (n = 1). Drug-related adverse events (AEs) of all grades were reported in 14 pts (77.8%) and grade 3 or 4 AEs were reported in 10 pts (55.6%). The most commonly reported AEs were anemia and nausea. No pharmacokinetic (PK) interaction was observed. Based on considerations of the statistical model, clinical assessment of safety, tolerability, PK, and pharmacodynamic results, maximum-tolerated dose and recommended dose were established as 400 mg of sonidegib in combination with the fixed standard dose of GEM (1000 mg/m2).The objective response rate was 11.1% and the median progression-free survival (PFS) was 4.9 months. Conclusions: The combination of sonidegib and GEM was generally well tolerated with moderate activity. Although no formal comparison can be made due to small sample size of this study, this combination provided a median PFS comparable to the current standard of care without conferring any additional clinical benefit. Clinical trial information: NCT01487785.

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A Matching-Adjusted Indirect Comparison of Sonidegib and Vismodegib in Advanced Basal Cell Carcinoma

Journal of Skin Cancer ◽

10.1155/2017/6121760 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 13

Author(s):

Dawn Odom ◽

Deirdre Mladsi ◽

Molly Purser ◽

James A. Kaye ◽

Eirini Palaka ◽

...

Keyword(s):

Basal Cell ◽

Comparative Effectiveness ◽

Small Sample Size ◽

Objective Response ◽

Locally Advanced ◽

Indirect Comparison ◽

Small Sample ◽

Curative Surgery ◽

Adjusted Indirect Comparison ◽

Baseline Characteristics

Objectives. Based on single-arm trial data (BOLT), sonidegib was approved in the US and EU to treat locally advanced basal cell carcinomas (BCCs) ineligible for curative surgery or radiotherapy. Vismodegib, the other approved targeted therapy, also was assessed in a single-arm trial (ERIVANCE). We examined the comparative effectiveness of the two drugs using a matching-adjusted indirect comparison (MAIC) versus an unadjusted indirect comparison. Methods. After comparing trials and identifying potential prognostic factors, an MAIC was conducted to adjust for differences in key patient baseline characteristics. Due to BOLT’s small sample size, the number of matching variables was restricted to two. Efficacy results for sonidegib were generated so that selected baseline characteristics matched those from ERIVANCE and were compared with published ERIVANCE results. Results. Matching variables were baseline percentages of patients receiving prior radiotherapy and surgery. After weighting, sonidegib objective response rate (ORR) and median progression-free survival (PFS) were effectively unchanged (prematched versus postmatched ORR and PFS, 56.1% versus 56.7% and 22.1 versus 22.1 months, resp.). Vismodegib’s ORR and PFS were 47.6% and 9.5 months. Conclusions. Comparative effectiveness of sonidegib versus vismodegib remains unchanged after adjusting BOLT patient-level data to match published ERIVANCE baseline percentages of patients receiving prior surgery and radiotherapy.

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Anti-PF4/Heparin Antibody Levels in Bacteremia, Fungemia and Sepsis

Blood ◽

10.1182/blood-2018-99-117917 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3752-3752

Author(s):

Satish Maharaj ◽

Simone Chang ◽

Karan Seegobin ◽

Fauzia Rana ◽

Marwan Shaikh

Keyword(s):

Immune Response ◽

Statistical Significance ◽

Small Sample ◽

Primary Immune Response ◽

Control Group ◽

Gram Positive ◽

Platelet Factor ◽

Gram Negative ◽

Significant Difference ◽

Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is caused by antibodies targeting platelet factor 4 (PF4)/heparin complexes. The immune response leading to HIT remains perplexing with many paradoxes. Unlike other drug induced reactions, anti-PF4/heparin antibody generation does not follow the classic immunologic response. As Greinacher and colleagues have shown, the primary immune response lacks IgM precedence and class switching, and heparin-induced antibodies can induce HIT by day 5 in heparin-naïve patients.Continued exposure to heparin also is puzzling with a weak or declining secondary immune response. Research by Krauel and colleagues suggests that that there is close interplay among infection, PF4 and the immune system. In 2010 they demonstrated that human and murine PF4 bind to Gram positive (S.aureus, S.pneumoniae, L.monocytogenes) and Gram negative (E.coli, N.meningitidis) bacteria in vitro, with bacterial surfaces acting as polyanions. High dose heparin inhibited this binding and anti-PF4/heparin antibodies from patients with HIT reacted with these PF4/bacterial complexes (S. aureus and E. coli). Using a murine model, they went on to show that polymicrobial sepsis in the absence of heparin led to antibody generation. In a separate study, Krauel and colleagues also showed that PF4 binds specifically to the lipid A component of Gram negative bacteria. In this analysis, we report on anti-PF4/heparin antibody levels in groups of patients hospitalized for sepsis, as compared to a control group without sepsis. We examined 200 patients with sepsis, retrospectively identified, from a hospital database of anti-PF4/heparin testing done in medical inpatients with thrombocytopenia but low pretest probability of HIT. This included patients with bacteremia (57), fungemia (7) and sepsis without septicemia (136). For comparison, data from 50 patients without sepsis during the same time period was used. Inclusion criteria for all groups were age 18 years and older and antibody testing within 4 days of admission. Exclusion criteria were diagnosis of HIT or heparin allergy, prior hospitalization or heparin exposure within 90 days of admission, cardiopulmonary bypass or orthopedic surgery within 6 months, hemodialysis, active or past malignancy, antiphospholipid syndrome, autoimmune disease or immunosuppressive therapy. All patients studied were on subcutaneous heparin at prophylactic doses only (i.e. no intravenous use, no therapeutic anticoagulation). UFH use predominated with prevalence of >85% in all groups. Testing was done using a commercially available standardized solid phase enzyme-linked immunoassay (EIA) to detect antibodies (IgG/IgA/IgM) directed against PF4 complexed with polyvinylsulfonate (Genetic Testing Institute, Wisconsin). All assays were performed in the central hospital laboratory according to manufacturer's specifications and measured in optical density (OD) units. The data sets demonstrated continuous unimodal distribution with high OD outliers, indicative of varying immune responses along a continuum. Statistical significance was calculated using independent t-testing with p-value set at 0.05 for significance. Results showed that patients hospitalized with sepsis have higher anti-PF4/heparin antibody levels. Both patients with bacteremia, and sepsis without bacteremia, had significantly higher OD than patients without sepsis (p<0.05). There was no significant difference between Gram negative and Gram positive bacteremia and antibody levels. This suggests that bacterial cell wall components of both classes have similar antigenicity. Interestingly, patients with fungemia had much lower antibody levels compared to bacteremia and sepsis. Despite the small sample size for fungemia, this difference trended strongly towards statistical significance (p=0.05). The threshold for a positive EIA is currently established at OD>0.400, a value based on sensitivity and set by the manufacturer. When the prevalence of a positive EIA was assessed, 16% patients with sepsis and bacteremia tested positive compared to 4% in the control group. In summary, there is an increased prevalence of anti-PF4/heparin antibodies in patients hospitalized with bacterial but not fungal sepsis. These results support the theory that bacterial infection has a role to play in preimmunization leading to anti-PF4/heparin antibody generation. Disclosures No relevant conflicts of interest to declare.

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Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation

British Journal of Cancer ◽

10.1038/s41416-019-0582-7 ◽

2019 ◽

Vol 122 (3) ◽

pp. 333-339 ◽

Cited By ~ 14

Author(s):

Max M. Wattenberg ◽

Daniella Asch ◽

Shun Yu ◽

Peter J. O’Dwyer ◽

Susan M. Domchek ◽

...

Keyword(s):

Objective Response ◽

Clinical Trial Design ◽

Progression Free Survival ◽

Ductal Adenocarcinoma ◽

Control Group ◽

Response Characteristics ◽

Platinum Based Chemotherapy ◽

Significant Difference ◽

Palb2 Mutation ◽

Brca1 Brca2

Abstract Background Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS) achieved with such treatment remain ill-defined. Methods Twenty-six patients with advanced-stage mut-positive PDAC who had been treated with platinum-based therapy were matched by age, race and sex to 52 platinum-treated control PDAC patients. Responses to therapy were determined by RECIST v1.1, performed by blinded radiology review. Measured outcomes included ORR and rwPFS. Results The ORR in mut-positive patients was 58% compared to 21% in the control group (p = 0.0022). There was no significant difference in ORR between platinum regimens in mut-positive patients (p = 0.814), whereas in control patients, the only observed responses were to FOLFIRINOX. rwPFS was 10.1 mo. for mut-positive patients and 6.9 mo. for controls (HR 0.43; 95% CI 0.25–0.74; 0.0068). Conclusion Mut-positive PDAC has a high ORR and prolonged rwPFS to platinum-based chemotherapy. These findings may have implications particularly in the neoadjuvant setting, and for future clinical trial design, and highlight the importance of early germline testing in patients with PDAC.

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Surgical outcomes and rate of pathological response in resectable/borderline resectable pancreatic cancer patients undergoing neoadjuvant gemcitabine/nab-paclitaxel versus FOLFIRINOX: A retrospective institutional analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16247 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16247-e16247

Author(s):

Abraham Attah Attah ◽

Saleha Rizwan ◽

Khaled Alhamad ◽

Micheal Turk ◽

Palash Asawa ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Treatment Response ◽

Surgical Resection ◽

Locally Advanced ◽

Small Sample ◽

Ductal Adenocarcinoma ◽

Categorical Variables ◽

Adjuvant Setting ◽

Borderline Resectable ◽

Significant Difference

e16247 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors, predicted to become the second leading cause of cancer related death in some regions of the world. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Only about 20% of the cases are diagnosed early enough to undergo surgical resection leading to complete remission. While chemotherapy has an established role in the setting of metastatic disease, utilizing it in the neo-adjuvant setting has been adopted by most institutes for resectable/ borderline resectable cases. Ongoing trials are exploring the use of different regimens in the neo-adjuvant setting. The aim of our study was to identify patients with resectable/borderline resectable PDAC undergoing neoadjuvant chemotherapy and differences in surgical outcome based on the regimen received i.e gemcitabine/ nab-Paclitaxel vs FOLFIRINOX. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Results: Out of 121 patients who received and completed treatment in our institution, 30 underwent neoadjuvant chemotherapy treatment followed by surgical intervention. 21 (70%) patients were found to be borderline resectable, 8 (27%) patients were resectable and 1 patient had locally advanced PDAC. 16 (53%) patients received FOLFIRINOX compared to 13 (43%) patients received gem/nab-paclitaxel. Among patients who received neoadjuvant FOLFIRINOX, 5 out of 16 (31%) patients had moderate to significant treatment response at the time of surgery compared to 7 out of 13 (54%) patients who received gemcitabine/nab-paclitaxel. Conclusions: Our study revealed no significant difference (p=0.21) between the patients who received neoadjuvant gemcitabine/nab-paclitaxel vs FOLFIRINOX in terms of treatment response assessed pathologically at the time surgical resection. We recognize the limitations of our study in terms of it being a retrospective analysis with a small sample size and therefore further prospective and randomized controlled trials are needed to determine the most suitable and effective regimen in the neoadjuvant setting for resectable/borderline resectable PDAC patients. Response to treatment among different chemotherapy groups.[Table: see text]

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