The comedian George Carlin once pointed out that of the many reasons to love the game of baseball, the most resonant is that if you hit the ball just right, you get to go home.
For the clinician, and the oncologist in particular there is no less of a goal – step up to the plate, study the pitch, time the swing, connect, and see how many bases the patient gets to run before the ball comes back and he gets thrown out.
All too often the patient never makes it off the base path, or worse, strikes out. But sometimes, and increasingly so, the patient gets to go home.
The analogy is apt considering the results of some of the high profile studies presented recently at ESMO 2014, held from September 26 – 30, 2014 in Madrid, Spain.
ESMO: The Homerun – CLEOPATRA
The impact of the overall survival (OS) data from CLEOPATRA cannot be overstated. Patients are going home.
As proclaimed by CLEOPATRA lead investigator, Sandra Swain, MD, Medical Director of the Washington Cancer Institute, “These data – which I think are phenomenal – confirm that this regimen is now the first-line standard of care for patients with HER2-positive metastatic breast cancer.”
The regimen in question is the new HER2/3-targeting agent pertuzumab, used in combination with the older, but highly effective HER2-targeting drug trastuzumab plus paclitaxel.
Testing the efficacy of this combination, CLEOPATRA enrolled over 800 HER2-positive, metastatic breast cancer patients at 204 medical centers in 25 countries; patients were randomized in a blinded fashion to the trastuzumab/paclitaxel doublet, plus or minus pertuzumab.
The ESMO results – the final reporting of survival data – showed that patients had a progression-free survival (PFS) favoring pertuzumab by 6.3 months; for OS the pertuzumab arm was 56.6 months versus 40.8 months for the doublet (p=0.002).
Once these data were announced, the reaction at the conference was profound. “An unprecedented success,” said Luca Gianni, MD, San Raffaele Cancer Center, Milan, Italy. “This is the new standard, and not an option for first-line treatment in this disease setting.”
There was more good news for metastatic breast cancer patients – this time in the HER2-negative population – in the reporting of the IMELDA trial.
In this randomized, phase 3 investigation, patients with advanced breast cancer were first treated with bevacizumab plus docetaxel for up to six cycles. Following this regimen, patients without measurable disease progression were put on maintenance therapy consisting of bevacizumab plus or minus capecitabine.
The rationale for this experiment was to see if switching to a more tolerable chemotherapy, with a different mechanism of action while continuing the VEGF blockade, would be more effective than the docetaxel-based combination.
The IMELDA endpoint was time to PFS. Results here, again, prompted immediate praise, this time from Hope Rugo, MD, the director of the breast cancer clinical trials program at the University of California, San Francisco.
“There was a markedly longer progression-free survival,” she said, “one you rarely see in treatment of advanced breast cancer that is HER2-negative.” PFS was 4.3 months with bevacizumab alone versus 11.9 months for the combination (p<0.001). The time to OS also favored the combination: 23.7 months versus 39 months (p=0.0003).
“It’s very nice to see that in a trial of HER2-negative breast cancer, overall survival is being extended,” said Dr. Rugo, adding that, “there is one important caveat here – at the time of reporting less than half of the patients on this trial have died, which is a rather pleasant complication to data analysis in a study of advanced breast cancer.”
A double in that the news was good, and there were two similar trials to prove it: coBRIM, which examined vemurafenib plus cobimetinib in BRAF-positive metastatic melanoma patients (N=495); and COMBI-v, which studied dabrafenib plus trametinib in roughly the same patient population (N=704).
In coBRIM, a 49% reduction in progression or death was observed versus vemurafenib alone; in COMBI-v alone a 31% reduction in the risk of death was noted (the COMBI-v data were more mature).