Same Data; Different Interpretations
Interpretation of oncology clinical trial data are not always
straightforward or consistent.
Similar trial results with disparate
interventions may be interpreted differently by the
oncology community. One of the main reasons for this discrepancy is the
debate regarding what is the appropriate end point for
demonstration of efficacy of cancer drugs. There is no doubt that
overall
survival (OS) is the best parameter to judge the
utility of any intervention, and it is free from bias in ascertainment
and
measurement
1; but for conditions with few treatment options and dire outcomes, the need for new agents is high and the oncology community
sometimes settles on a surrogate end point that, in many cases, is progression-free survival (PFS).
2
It is easy to understand why PFS is favored among the researchers: It
occurs early and is not influenced by postprogression
therapy. At the same time, it would make little sense
to have an agent that reduces chances of dying of cancer but increases
off-target deaths; hence, the need for verification of
OS. Phase III trials that report on significant PFS benefits without
OS prolongation become the apples of discord in the
oncology community. In this commentary,
we present three examples from
lung, ovarian, and breast cancers and demonstrate how
the oncology community interprets similar data differently. Finally,
we take our best guess as to why this phenomenon
happens.
Ovarian Cancer: Angiogenesis Inhibitors and Dose-Dense Chemotherapy
Several attempts have
been made to build on the success of the platinum-taxane combination
for treating advanced or metastatic
ovarian cancer, but none have been met with
irrefutable success. Of those various strategies, two are the most
common and
the most debated: dose-dense treatment schedule
and addition of an angiogenesis inhibitor to the combination.
The feasibility and efficacy of a dose-dense schedule (weekly paclitaxel
v every-3-week paclitaxel) was demonstrated in the Japanese Gynecologic Oncology Group (JGOG) 3016 trial, a study among 637
Japanese patients.
10 This trial showed that weekly paclitaxel improved both PFS and OS. The OS advantage was not trivial; it was a sizable 38-month
extension (100.5 months
v 62.2 months; HR, 0.79;
P
= .039). However, the global oncology community adopted the addition of
bevacizumab but has
largely ignored the dose-dense
paclitaxel schedule. Perhaps, the large benefit
with weekly paclitaxel prompted clinicians to disbelief and wanting
further
confirmation; yet, it is hard to imagine
clinicians believed a larger benefit would altogether vanish, rather
than merely
be attenuated........

We cannot also ignore the deep issues beyond clinical data that result
in discrepancies in cancer care, such as politics,
emotional overlay, lobbying, and advocacy of
support groups. Although we explore three instances of discrepancies in
the treatment
of three similar cancer settings in this paper,
many discrepancies exist in cancer care. When bevacizumab was revoked
for
breast cancer, support groups and patient
advocates protested against the decision, but when
131I-tositumomab
was withdrawn from marketing, it died silently. Thus, our attitudes
toward cancer care are multifactorial. As
oncologists, however, we should push for
uniformity in the interpretation of clinical trial results and try to
achieve as
much consistency in our practice as possible.
Consistency would be a virtue for cancer care.