A consensus report issued by the National Cancer
Institute has called for enhanced clinical and translational research and
improved partnerships among those who manage pancreatic ductal adenocarcinoma.
The NCI’s Gastrointestinal Cancer Steering
Committee organized a two-day meeting with representatives from the patient
advocacy community, pharmaceutical industry and government agencies to discuss
the integration of basic and clinical knowledge in the design of clinical
trials for pancreatic ductal adenocarcinoma. The group’s major focus was
defining the direction for clinical research into the disease for the next
three to five years.
There were four major objectives for the meeting:
Address critical questions and unmet needs in treatment and translational
research for pancreatic ductal adenocarcinoma; assist innovation and
collaboration among clinical and basic investigators; develop strategic
priorities for clinical trials in the future; and address ways to distribute
these priorities to the relevant oncology communities.
The committee review, published online in the Journal
of Clinical Oncology, listed recommendations for five major areas for
improving research including developing new targets for drug development;
rethinking the utility of preclinical models; redesigning clinical trials,
especially phase-3 trials; establishing biorepositories; and developing
biomarkers.
In an accompanying editorial, Josep Tabernero,
MD, and Teresa Macarulla, MD,, both of the Vall d’Hebron
University Hospital in Barcelona, Spain, said the recommendations should be
strongly considered when developing future trials. They noted that physicians
have learned little from phase-3 trials of the past 20 years that has helped
patients.
“Most of the cooperative groups involved in the
treatment of patients with advanced pancreatic cancer have learned these
historical lessons of limited success and are implementing these new concepts
in the clinical development of new therapeutic strategies,” they wrote.
“Hopefully, this change in the developmental path will translate into
better options for patients with advanced pancreatic cancer.”
The committee said research needs to focus on developing
new molecular targets for therapy including genetic alterations in pancreatic
tumors and epigenetic changes. They listed the KRAS oncogene, epidermal
growth factor receptor, PI3 kinase, and the hedgehog pathways as some of the
more promising targets.
Those who treat pancreatic ductal adenocarcinoma also
need new agents to attack those new targets; cytotoxic drugs, alone or in
combination with targeted agents, are crucial for remedying pancreatic cancer,
according to the committee.
Toward that end, they said developing phase-2 trials
with a high chance of success in later phase-3 testing is a priority. OS should
remain the primary endpoint for such trials, and patients must be carefully
selected and monitored.
“The ability to select patients based on predictive
biomarkers may reduce the number of patients required in subsequent phase-3
trials,” the committee wrote.
Although the committee acknowledged that a vaccine is
unlikely to be successful alone, vaccines may play a role when combined with
standard therapies due to the inherent immunogenicity of some chemotherapeutic
and targeted agents.
The committee concluded by indicating it will take a
collaboration between “the academic community and the pharmaceutical
industry” to find a cure.
“The NCI and other public and private agencies and
organizations must increase funding for basic, clinical and translational
research in pancreatic cancer relative to priorities as defined by the
community and include methods to evaluate and refine the process in a dynamic
manner,” they wrote. “Active involvement by patient advocates and
community physicians as well as the ongoing efforts within the NCI to simplify
the protocol development process will hopefully facilitate the necessary
advances in this deadly disease.”
Philip PA. J Clin Oncol. 2009;doi:10.1200/JCO.2009.21.9022.
Tabernero J. J Clin Oncol. 2009;doi:10.1200/JCO.2009.23.3098.
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