Maurie Markman, MD

Oncologists Need Guideposts for Recommending Drugs Not Studied in Cancers

How can a conscientious but very busy practitioner keep up with the massive quantity of molecular data that could potentially impact an individual patient with cancer? The Moores Cancer Center at the University of California, San Diego has updated the tumor board concept for the molecular era.

Scarcely a week goes by without a report in the peer-reviewed medical literature suggesting that a novel somatic genomic alteration or a specific normal polymorphism is potentially relevant to achieving a desirable clinical outcome within cancer medicine.

There is a tension in the air these days when it comes to the manner in which evidence-based oncology research should be conducted in this revolutionary era, and that tension is evident on the pages of peer-reviewed articles describing novel findings in clinical molecular oncology, in editorials discussing these studies, and in commentaries related to future approaches to discovery.

Although oncology researchers seek to describe the significance of clinical trial outcomes with scientific rigor, the terminology used to communicate those findings in the peer-reviewed literature sometimes falls short in conveying the impact that a given therapy may have on patients in a real-world scenario.

Essentially all members of the medical community, including the most "generalist" family practice physicians, are being required to understand and incorporate into their daily practice an ever-increasing quantity of information related to the broad realm of molecular medicine

It seems that rarely a month goes by these days without the publication of a major study demonstrating the impact of fresh knowledge regarding molecular abnormalities in a particular tumor type.

Ostensibly, the illness is the culprit. But it is also the cancer patient who is made culpable

The readministration of a cytotoxic antineoplastic agent is a well-established management paradigm in a number of malignancies, yet it is generally believed such a strategy may not prove beneficial if the patient experiences disease progression while receiving the therapy.

The lack of documented superiority in a given randomized oncology trial may not indicate the absence of clinical utility but rather the presence of equivalent favorable activity for each of the two agents.

A recent study determined that it would take 6.7 years on average to enroll enough patients with pancreatic cancer for the trials that opened in 2011-a tall order considering that the 5-year relative survival rate for those diagnosed with pancreatic ductal adenocarcinoma is only 6%.

There has been considerable discussion within the oncology literature during the past several years regarding the level of evidence required to consider a new antineoplastic agent an acceptable "standard-of-care" in routine disease management.

How should the dose and schedule of antineoplastic therapies be modified in patients with known chronic liver, cardiac, or pulmonary disease when these conditions were excluded from the trials that permitted their routine clinical use? How should treatment be changed in the presence of significant obesity?

While a number of biological and clinical factors differentiate so-called "solid" from "liquid" cancers, there is perhaps no single difference that is more relevant than the ability in liquid cancers to easily obtain malignant cells from the blood for subsequent analysis in the laboratory.

A recognized recurring theme in many population-based cancer genetic studies is the highly provocative presence of a quite small percentage of tumors that possess specific molecular abnormalities unequivocally demonstrated to be "actionable," at least in one clinical setting.

Maurie Markman, MD, senior vice president for Clinical Affairs and National Director for Medical Oncology, Cancer Treatment Centers of America, Eastern Regional Medical Center, discusses the role of molecular testing in gynecologic cancers.

In many circumstances, the absence of so-called definitive evidence does not equate with the absence of evidence, just the level required by some to declare an approach to be an acceptable standard-of-care option.

It is well recognized that advances in cancer management have most often resulted from a close collaboration between clinical and laboratory investigative efforts.

Maurie Markman, MD, from the Cancer Treatment Centers of America, discusses the discovery of mutations and targets in ovarian cancer and the current progress being made in the development of a "breakthrough" agent for ovarian cancer.

Two teams of investigators report that analysis of germline polymorphisms yields valuable clues about which patients may experience adverse events from anticancer therapies.

Patients diagnosed with cancer today are considered to be genuine partners in all major treatment decisions. Yet, how well do they understand the nature and goals of genetic testing that might be recommended as part of the management of their disease?

Should an individual patient be denied the opportunity to potentially achieve the benefits from a therapeutic strategy because it is predicted that his or her tumor will have a relatively low chance to respond?

Clinical judgment may appropriately decide that based on a particular patient's medical status it may not be in that individual's best interest to undergo guideline-based therapy.

The security of genetic data collected from research study participants has emerged as a concern after investigators proved they could ferret out individual identities from large databases.

Two recent reports have challenged certain assumptions in the drug development process that raise ethical concerns, individually and collectively, which the clinical cancer research community must address.

A clinical commentary by Maurie Markman, MD, addressing whether overall survival can still be considered the sole acceptable primary endpoint in studies of novel anticancer therapeutic strategies.

Recently reported data demonstrate that the presence of a specific mutation in PDGFRA predicts for the lack of activity for the imatinib in patients with gastrointestinal stromal tumors.

Despite all we have learned about the importance of sensitizing EGFR mutations in defining the management of advanced NSCLC, our education regarding the relevance of this molecular target in optimizing clinical outcomes continues.

Maurie Markman, MD, asks who should decide whether it is ethically valid to consider off-label treatment in a patient with a very serious medical illness.

In the absence of a phase III randomized trial, what constitutes sufficient evidence to justify use of a treatment, particularly a nontraditional treatment or one that challenges common practice?