Olaparib for BRCA mutant pancreas cancer: Should the POLO trial change clinical practice?

Nishikawa, Go; Booth, Christopher M.; Prasad, Vinay

doi:10.1002/cncr.32979

Cited by 8 publications

(6 citation statements)

References 8 publications

(8 reference statements)

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“…In light of these findings, the FDA has approved olaparib for maintenance therapy in patients with metastatic PDAC patients with germline mutations of BRCA1/2 who have not progressed on at least 16 wk of first-line PtCh. This approval is not without controversy as there are several criticisms of the POLO trial and unanswered questions in regards to this therapy[ 74 ]. For example, the lack of improvement in OS puts the validity of the finding of improved PFS into question[ 74 ].…”

Section: Management Of Brca-mutated Pdac: Systemic Therapymentioning

confidence: 99%

“…This approval is not without controversy as there are several criticisms of the POLO trial and unanswered questions in regards to this therapy[ 74 ]. For example, the lack of improvement in OS puts the validity of the finding of improved PFS into question[ 74 ]. However, this may be because of the high rates of therapy in the placebo group following disease progression, including 15% of the patients who received a PARP inhibitor.…”

Section: Management Of Brca-mutated Pdac: Systemic Therapymentioning

confidence: 99%

“…In addition, it should be stated that the OS results were from an interim analysis with only 46% data maturity. Furthermore, concern has been raised that the discontinuation of PtCh after 16 wk in patients who were responding is incongruent with clinical practice guidelines for first-line platinum chemotherapy[ 74 ]. However, in the POLO trial, the majority of patients received FOLFIRINOX (> 80%) with a median duration of first line PtCh of 5 mo and 33% of patients receiving > 6 mo prior to randomization[ 72 ].…”

Section: Management Of Brca-mutated Pdac: Systemic Therapymentioning

confidence: 99%

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BRCA mutated pancreatic cancer: A change is coming

Rosen

Goodwin

Vickers

2021

WJG

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Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced disease. Recently, patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast tumors. Germline BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8% of patients with sporadic pancreatic cancer. In patients with germline BRCA mutations, platinum-based chemotherapies and poly (ADP-ribose) polymerase inhibitors are effective treatment options which may offer survival benefits. This review will focus on the molecular biology, epidemiology, and management of BRCA -mutated pancreatic cancer. Furthermore, we will discuss future directions for this area of research and promising active areas of research.

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Section: Management Of Brca-mutated Pdac: Systemic Therapymentioning

confidence: 99%

Section: Management Of Brca-mutated Pdac: Systemic Therapymentioning

confidence: 99%

Section: Management Of Brca-mutated Pdac: Systemic Therapymentioning

confidence: 99%

See 1 more Smart Citation

BRCA mutated pancreatic cancer: A change is coming

Rosen

Goodwin

Vickers

2021

WJG

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“…65 In addition to the lack of overall survival benefit, concerns have been raised with the design of the study including placebo instead of 5-FU monotherapy. 66 Moreover, olaparib associated health care costs with lack of overall survival benefit is further concerning.…”

Section: Role Of Parpi In Pancreatic Ductal Adenocarcinomamentioning

confidence: 99%

Current Systemic Treatments for the Hereditary Cancer Syndromes: Drug Development in Light of Genomic Defects

Hasanov

Pimentel

Cruellas

et al. 2022

American Society of Clinical Oncology Educational Book

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Advances in the genetic basis of different tumors have led to identification of tumor vulnerabilities that can be turn into targeted therapies. In this regard, PARP inhibitors cause synthetic lethality with tumors harboring BRCA1 or BRCA2 genetic alterations. On the other hand, tumors with microsatellite instability, either due to germline or sporadic alterations, are candidates for immune checkpoint inhibitors. Finally, patients with von Hippel-Lindau disease who carry a germline alteration in the VHL gene may benefit form belzutifan, a hypoxia-inducible factor 2 alpha inhibitor. Overall, research on the underlying pathological mechanisms of these tumors has provided new therapeutic opportunities that might be expanded to other sporadic tumors with similar biology.

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“…In mutation carriers deriving clinical benefit from a first line platinum-based CT, whether to maintain the initial regimen, to deescalate to a maintenance CT regimen without platinum, to stop all CT after 6 months or to switch to olaparib remain unanswered questions. It is a matter of debate whether, in the absence of an OS benefit and in the presence of some design flaws (absence of an active control arm), the POLO trial can change the standard of care ( 99 ). Certainly, it is a new option in a field where targeted and maintenance therapy are urgently required.…”

Section: Options In the Treatment Of Metastatic Diseasementioning

confidence: 99%

Treatment optimization of locally advanced and metastatic pancreatic cancer (Review)

Barros¹,

Pulido

Machado

et al. 2021

Int J Oncol

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being the sixth leading cause of mortality worldwide and the fourth in Europe. Globally, it has a mortality/incidence ratio of 98%, and the 5-year survival rate in Europe is only 3%. Although risk factors, such as obesity, diabetes mellitus, smoking, alcohol consumption and genetic factors, have been identified, the causes of PDAC remain elusive. Additionally, the only curative treatment for PDAC is surgery with negative margins. However, upon diagnosis, ~30% of the patients already present with locally advanced disease. In these cases, a multidisciplinary approach is required to improve disease-related symptoms and prolong patient survival. In the present article, a comprehensive review of PDAC epidemiology, physiology and treatment is provided. Moreover, guidelines on patient treatment are suggested. Among the different available therapeutic options for the treatment of advanced PDAC, results are modest, most likely due to the complexity of the disease, and so the prognostic remains poor. Molecular approaches based on multi-omics research are promising and will contribute to groundbreaking personalized medicine. Thus, economic investment that promotes research of pancreatic cancer will be critical to the development of more efficient diagnostic and treatment strategies.

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Olaparib for BRCA mutant pancreas cancer: Should the POLO trial change clinical practice?

Cited by 8 publications

References 8 publications

BRCA mutated pancreatic cancer: A change is coming

BRCA mutated pancreatic cancer: A change is coming

Current Systemic Treatments for the Hereditary Cancer Syndromes: Drug Development in Light of Genomic Defects

Treatment optimization of locally advanced and metastatic pancreatic cancer (Review)

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