Page 65 - Read Online

Rosenzweig et al. J Cancer Metastasis Treat 2022;8:46 https://dx.doi.org/10.20517/2394-4722.2022.58 Page 3 of 9

Figure 1. Novel clinical trial designs include basket, umbrella, and platform trials. Adapted from [10] .

A platform clinical trial design allows multiple investigational treatment options to be tested in parallel
[10]
against a single or several standard-of-care arms . With constant evaluation of data and careful statistical
analyses, it can quickly be determined whether a treatment arm is showing promise or faring poorly.
Treatment arms can go on or off the platform, potentially allowing the trial to go on in perpetuity. Platform
trials can also be designed to straddle two phases - phase I and II or phase II and III - to facilitate a
smoother transition between dose escalation and dose expansion or to move more quickly from a positive
efficacy signal to registration for approval.

With the poor clinical outcomes of pancreatic cancer and the lack of responsiveness to conventional and
newer (e.g., immunotherapy) solid tumor treatment options, it is time to develop new approaches to
combat this deadly cancer, as well as new ways to identify, develop and test new treatment options. Here in
this opinion paper, we discuss the current standard of care for pancreatic adenocarcinoma in the U.S. and
some recent innovations in clinical trials for pancreatic cancer, which provide hope for accelerated progress
in the near future.

APPROVED TREATMENTS FOR PANCREATIC ADENOCARCINOMA IN THE UNITED
STATES
Advances in the treatment of pancreatic adenocarcinoma in the U.S. depend primarily on clinical research
leading to FDA approval for new treatment entities, although successful clinical trials with agents that are
off-patent have also changed the standard. Progress was slow between 1995 and 2015; gemcitabine became
the standard of care for metastatic pancreatic adenocarcinoma in 1996 , FOLFIRINOX was added in
[13]
[14]
[15]
2010 , and the combination of gemcitabine and nab-paclitaxel was FDA approved in 2013 [Table 1].
However, since 2015 there has been a remarkable increase in new treatments for specific disease states or
sub-populations of patients. With FOLFIRINOX and gemcitabine plus nab-paclitaxel both considered
effective standard-of-care options for metastatic patients, research efforts resulted in the first FDA approval
of second-line treatment of 5-FU + nal-irinotecan for metastatic pancreatic adenocarcinoma patients who
[16]
received gemcitabine in the first line . There have also been accepted clinical advances resulting in the
widespread use of gemcitabine-based or FOLFIRINOX-based regimens for adjuvant treatment for earlier-
stage pancreatic adenocarcinoma [17,18] . Additionally, a number of approvals for biomarker-identified subsets
of patients in tumor-agnostic studies impact a small number of pancreatic adenocarcinoma patients with