Randomized phase 2 study of PEGPH20 Plus nab-paclitaxel/gemcitabine (PAG) vs AG in patients (Pts) with untreated, metastatic pancreatic ductal adenocarcinoma (mPDA)

Hingorani, Sunil R.; Bullock, Andrea J.; Seery, Tara Elisabeth; Li, Zheng; Sigal, Darren; Ritch, Paul S.; Braiteh, Fadi; Zalupski, Mark M.; Bahary, Nathan; Harris, William Proctor; Pu, Jie; Aldrich, Carrie; Khelifa, Sihem; Wilson, William R.; Chondros, D.; Jiang, Ping; Hendifar, Andrew Eugene

doi:10.1093/annonc/mdx369.145

Cited by 4 publications

(5 citation statements)

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“…The search and selection process is shown in Figure 2. From the search results we have included 98 articles, of which 51 are congress abstracts, which describe anti-stromal therapies in pancreatic adenocarcinoma [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,…”

Section: Resultsmentioning

confidence: 99%

Clinical Trials Targeting the Stroma in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Mackelenbergh

Stroes

Spijker

et al. 2019

Cancers

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The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an overview of clinical trials with stroma-targeting agents. We systematically searched MEDLINE/PubMed and the EMBASE database, using the PRISMA guidelines, for eligible clinical trials. In total, 2330 records were screened, from which we have included 106 articles. A meta-analysis could be performed on 51 articles which describe the targeting of the vascular endothelial growth factor (VEGF) pathway, and three articles which describe the targeting of hyaluronic acid. Anti-VEGF therapies did not show an increase in median overall survival (OS) with combined hazard ratios (HRs) of 1.01 (95% confidence interval (CI) 0.90–1.13). Treatment with hyaluronidase PEGPH20 showed promising results, but, thus far, only in combination with gemcitabine and nab-paclitaxel in selected patients with hyaluronic acid (HA)high tumors: An increase in median progression free survival (PFS) of 2.9 months, as well as a HR of 0.51 (95% CI 0.26–1.00). In conclusion, we found that anti-angiogenic therapies did not show an increased benefit in median OS or PFS in contrast to promising results with anti-hyaluronic acid treatment in combination with gemcitabine and nab-paclitaxel. The PEGPH20 clinical trials used patient selection to determine eligibility based on tumor biology, which underlines the importance to personalize treatment for pancreatic cancer patients.

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Section: Resultsmentioning

confidence: 99%

Clinical Trials Targeting the Stroma in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Mackelenbergh

Stroes

Spijker

et al. 2019

Cancers

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“…This was investigated in the phase 2 HALO-202 study and reported improved median progression- free survival in the PDC patients receiving PEGPH20 with gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel alone. 61 In the secondary endpoint analysis of patients with high levels of hyaluronan, the median PFS increased to 9.2 months from 5.2 months in favor of combination PEGPH20 and chemotherapy. Therefore, hyaluronan-high status has been considered as a potential predictive biomarker of benefit of PEGPH20 in PDC.…”

Section: Predictive Biomarkersmentioning

confidence: 97%

“…Therefore, hyaluronan-high status has been considered as a potential predictive biomarker of benefit of PEGPH20 in PDC. 61 The combination of hyaluronidase with immunotherapies is currently under validation in a phase 3 trial. 62…”

Section: Predictive Biomarkersmentioning

confidence: 99%

Advances in pancreatic cancer biomarkers

Hasan¹,

Jacob²,

Manne³

et al. 2019

Oncol Rev

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Biomarkers play an essential role in the management of patients with invasive cancers. Pancreatic ductal adenocarcinoma (PDC) associated with poor prognosis due to advanced presentation and limited therapeutic options. This is further complicated by absence of validated screening and predictive biomarkers for early diagnosis and precision treatments respectively. There is emerging data on biomarkers in pancreatic cancer in past two decades. So far, the CA 19-9 remains the only approved biomarker for diagnosis and response assessment but limited by low sensitivity and specificity. In this article, we aim to review current and future biomarkers that has potential serve as critical tools for early diagnostic, predictive and prognostic indications in pancreatic cancer.

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“…Auf dem ASCO und ESMO 2017 wurden nun die Ergebnisse der randomisierten HALO-202-Studie vorgestellt. Diese Phase-I/II-Studie vergleicht die Kombination aus Gemcitabin und nab-Paclitaxel ± PEGPH20 in der palliativen Erstlinientherapie [41,42]. Primärer Endpunkt der Studie war das progressionsfreie Überleben und als zusätzlicher primärer Sicherheits-Endpunkt die Rate an thromboembolischen Ereignissen bei bekannter Risikozunahme unter PEGPH20-Therapie.…”

Section: Pankreaskarzinom: Tumorstroma Als Zielunclassified

“…Auch im Gesamtüberleben zeigt sich ein Trend zugunsten des experimentellen Prüfarms. In Bezug auf das Tumoransprechen zeigte sich ein Vorteil der Kombinationstherapie mit PEGPH20 insbesondere in der HA-high-Population (ORR-Rate: Gesamtpopulation: 40 vs. 33 %, HA-high-Population: 45 vs. 31 %) [41,42]. Diese hoffnungsvollen Daten insbesondere in der Subpopulation der Patienten mit hohem Hyaluronsäure-Gehalt im Tumorstroma werden aktuell in einer internationalen Phase-III-Studie an dieser Subpopulation evaluiert (Halo-301-Studie, NCT02 715 804).…”

Section: Pankreaskarzinom: Tumorstroma Als Zielunclassified

ASCO- und ESMO-Update 2017 – Neuigkeiten vom 53. Meeting der American Society of Clinical Oncology/ASCO 2017 und European Society for Medical Oncology/ESMO-Congress 2017

et al. 2018

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At ASCO 2017, and subsequently the ESMO congress 2017, a number of studies were presented which, in part, may change the present standard of therapy in gastrointestinal oncology. The German FLOT4 trial established perioperative Docetaxel, Oxaliplatin and 5-Fluorouracil (5-FU) as the new treatment standard for resectable adenocarcinoma of the gastroesophageal junction and the stomach. In hepatocellular carcinoma (HCC), two large studies did not show a survival benefit for selective internal therapy (SIRT), so an increasing use of SIRT in HCC is not recommended. On the other hand, the multityrosinekinase inhibitor Lenvatinib seems to be a promising alternative to sorafenib in first line treatment of metastatic HCC. In early colon cancer-following the data from the large IDEA initiative-three months of capecitabine and oxaliplatin is recommended for low-risk stage III cancers (T1 - 3, N1), while in high-risk stage III cancers (T4 or N2) patients should still receive six months of oxaliplatin and a fluoropyrimidine. Aside from regular exercise, one study found that regular intake of tree nuts (at least 2 servings per week), may decrease the risk of recurrence. In first line metastatic colorectal cancer (mCRC), SIRT should not be applied, whereas in BRAF mutant cancers, the combination of irinotecan, cetuximab and vemurafenib seems to be a promising second line treatment option. In biliary tract cancer, after curative resection, six months of capecitabine is considered the new treatment standard. Finally, in pancreatic cancer, targeting the tumor stroma with pegylated hyaluronidase (PEGPH20) may be a new treatment option that needs to be proven in phase 3 studies.

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Randomized phase 2 study of PEGPH20 Plus nab-paclitaxel/gemcitabine (PAG) vs AG in patients (Pts) with untreated, metastatic pancreatic ductal adenocarcinoma (mPDA)

Cited by 4 publications

References 0 publications

Clinical Trials Targeting the Stroma in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Clinical Trials Targeting the Stroma in Pancreatic Cancer: A Systematic Review and Meta-Analysis

Advances in pancreatic cancer biomarkers

ASCO- und ESMO-Update 2017 – Neuigkeiten vom 53. Meeting der American Society of Clinical Oncology/ASCO 2017 und European Society for Medical Oncology/ESMO-Congress 2017

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