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Note
The first ace was dealt just after Thanksgiving when the
NCI issued a press release indicating that ECOG trial E3200
demonstrated a survival advantage for the addition of bevacizumab
to FOLFOX as second-line therapy for advanced colorectal
cancer. The many oncologists who, over the course of 18 months,
had already begun to adopt this regimen as first-line therapy
collectively exhaled in quiet relief. In a subsequent interview
for our lung cancer series, Eric Rowinsky boldly predicted
that in five years, “VEGF inhibitors will be used across
the board with all chemotherapy regimens.”
A few months later, another ace slid across the table.
It was March 13, and the NCI — about to enter the Guinness
Book of World Records for the most clinical trial press
releases in a year — told us that another ECOG study
(E4599) demonstrated a survival advantage for the addition
of bevacizumab to chemotherapy — this time in non-small
cell lung cancer.
 Alan
Sandler, the principal investigator of E4599, was previously
interviewed for our lung cancer series, and at that time,
like an expectant father who has no idea of his baby’s
due date, Alan was waiting for the ECOG data monitoring committee
to tell him when and whether this research concept would
deliver.
A couple of months later, and just a few days after the
NCI press release, I again interviewed Alan. The smile on
his face had grown considerably since our last meeting. No
wonder. It’s been a long while since a study in this
patient population resulted in a survival advantage. Based
on these results, it may be that platinum-taxane-bev triplets
will become the standard of care as first-line therapy for
non-small cell lung cancer in the near future.
The third ace came just weeks later when the busy workers
at the NCI press release factory jettisoned another bombshell:
A third ECOG study (may the Force be with you, Jedi Sledge)
met its primary endpoint by demonstrating a progression-
free survival advantage for the addition of — you guessed
it — bevacizumab to paclitaxel as first-line therapy
for metastatic breast cancer. Strangely enough, just a few
days earlier I was in Indianapolis recording an interview
with Kathy Miller, the principal investigator of ECOG trial
E2100, for our oncology nursing audio series. Here is a snippet
of our conversation:
DR LOVE: You’re
the third car in the bevacizumab race. I just interviewed
Alan Sandler about the bevacizumab lung trial a couple
of weeks ago, so you’re next and I say that it’s
going to happen.
DR MILLER: I
am hoping so, but it’s probably no surprise that
the PI of the trial firmly believes it will be positive.
Hopefully, this will not be yet another reminder that
I can firmly believe something and be proven wrong.
DR LOVE: What’s
the latest in terms of when you think the data might
be available?
DR MILLER: As
the PI, I review all of the events, both good and bad,
and to avoid any potential bias, all I’m allowed
to know is that the study will be reviewed by the ECOG
Data Monitoring Committee (DMC) at their next meeting,
which is five days from today.
DR LOVE: Five
days from now!
DR MILLER: Yes,
and that is all I am allowed to know. After reviewing
the data, they will give their recommendation as they
always do.
DR LOVE: Is this
a planned review?
DR MILLER: Yes,
and their recommendation could be to continue to follow
the patients as per protocol, or to release the data — either
because of clearly positive or clearly negative results.
DR LOVE: Theoretically,
have enough events occurred so that if the trial is
positive, we would know it?
DR MILLER: I
am not allowed to know that. The ECOG operations and
statistical folks are appropriately fanatical about
avoiding any potential for bias. This is the first
efficacy review. The other reviews have been only on
the toxicity data, and they have always indicated no
toxicity concerns and that the trial should continue.
DR LOVE: I see
a late-breaking ASCO thing in your future.
DR MILLER: Deadlines
are not favorable for that this year.
DR LOVE: Forget deadlines.
DR MILLER: I’m
holding out hope for the San Antonio meeting later
this year, Neil, because if the DMC at this meeting
suggests that the results should be made public, then
we’ll have that data in time for that deadline.
I must say that I am truly sick of people calling and
saying, “When? When?” and I’m sure
that the ECOG statisticians are equally tired of my
calling and emailing them. But it’s likely that
within a week or two after that DMC meeting, I’ll
hear whether the results tell us something other than
to continue on and keep waiting. |
Kathy’s wait ended soon after that and, deadlines
aside, she did in fact present these data in Orlando to the
multitudes at ASCO. In the interview, she discussed a pilot
trial evaluating bevacizumab in the adjuvant breast cancer
setting, and clearly the momentum to study this question
will now increase considerably.
Finally, on April 26, after fervently committing to take
the day off for my birthday, I succumbed to temptation and
checked my email. Sure enough, the fourth and most spectacular
ace had just been dealt, and Edith Perez’s “heads
up” in an interview just published in Breast Cancer
Update had come to pass. In what is destined to be one
of the sentinel moments in clinical cancer research, the
NCI press release gremlins let us know that the combined
analysis of the NSABP and Intergroup adjuvant trastuzumab
breast cancer trials demonstrated a whopping 52 percent reduction
in relapse rate for patients receiving trastuzumab. Edward
Romond presented this at ASCO soon after Kathy’s presentation.
Notwithstanding the Monday morning quarterbacking that
this monumental data set will generate, because of the tens
of thousands of patients with HER2- positive disease who
were not offered off-protocol trastuzumab, this study will
be viewed by some as the “end of the beginning” of
the war on cancer. Or is it the beginning of the end? This
unprecedented quartet of clinical trial results will undoubtedly
be discussed endlessly at CME meetings and tumor boards internationally,
and the impact on the daily management of patients with these
three most common solid tumors will be immediate and dramatic.
In this program, Bruce Giantonio reviews the first of the
four studies, ECOG-E3200, and Lee Ellis, Philip Philip and
Bob Diasio weigh in on what these data and other recent trial
results mean for clinical practice and future research. Cancer
patients and their oncologists needed a morale boost after
what has seemed to be glacier-like progress in this devastating
disease. With these four spectacular aces in hand, it’s
time to put down some serious money on prospects for the
future.
— Neil Love, MD
NLove@ResearchToPractice.net
NCI press releases
Bevacizumab Combined with Oxaliplatin-Based Chemotherapy
Prolongs Survival for Previously Treated Patients with Advanced
Colorectal Cancer: www.nci.nih.gov/newscenter/pressreleases/
BevacizumabOxaliplatin
Bevacizumab Combined with Chemotherapy Prolongs Survival
for Some Patients with Advanced Lung Cancer: www.nci.nih.gov/newscenter/pressreleases/AvastinLung
Bevacizumab Combined with Chemotherapy Improves Progression-Free
Survival for Patients with Advanced Breast Cancer: www.nci.nih.gov/newscenter/pressreleases/AvastinBreast
Herceptin® Combined with Chemotherapy Improves Disease-Free
Survival for Patients with Early- Stage Breast Cancer: www.nci.nih.gov/newscenter/pressreleases/HerceptinCombination2005
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