Leading Researcher Sees Turning Point in Breast Cancer: An Interview With José Baselga, MD, PhD

Anita T. Shaffer @Shaffer1
Published: Thursday, May 10, 2012
Dr. Jose Baselga at SABCS

Photo by ©SABCS/Todd Buchanan

José Baselga, MD, PhD, discusses the CLEOPATRA study during the 2011 CTRC-AACR San Antonio Breast Cancer Symposium in December.

In a six-week span, José Baselga, MD, PhD, notched a stunning series of milestones in breast cancer research: the publication of the results of three separate clinical trials with the potential to change practice in different subtypes of the disease.
Baselga is the lead author on: (1) BOLERO-2, which found a significant progression-free survival (PFS) benefit for combining everolimus (Afinitor) with exemestane in postmenopausal women with estrogen receptor-positive, HER2-negative metastatic breast cancer1; (2) CLEOPATRA, which established a PFS benefit for using the novel therapeutic pertuzumab with trastuzumab (Herceptin) as a dual HER2 blockade for HER2-positive patients with late-stage disease2; and (3) NeoALTTO, which found that administering lapatinib (Tykerb) plus trastuzumab in the neoadjuvant setting for HER2-positive patients produced a significant advantage in pathologic complete response.3

It was perhaps a once-in-a-lifetime confluence of events in a lifetime of achievement for an oncology leader who has spent more than 20 years in the field. Baselga built the oncology program at Vall d’Hebron University Hospital in Barcelona, Spain, into an internationally known research institute and served as president of the European Society of Medical Oncology. Earlier in his career, he completed a fellowship in medical oncology at Memorial Sloan-Kettering Cancer Center, New York, New York.

Two years ago, Baselga was named chief of the Division of Hematology/Oncology and associate director of the Massachusetts General Hospital (MGH) Cancer Center in Boston. MGH, which conducts nearly 400 clinical trials annually, has established one of the nation’s most extensive tumor genotyping initiatives.

For much of his career, Baselga has been exploring HER2 gene mutations in breast cancer. His work includes research that led to the development of trastuzumab (Herceptin) for the treatment of HER2-positive disease in the 1990s.

During a recent interview, Baselga couched his latest research highlights in modest terms. “You do multiple things, and to have more than one project coming to the end at the same time and having the three studies positive—that’s never going to happen again,” he said. “It’s just a coincidence.”

On the subject of breast cancer research as a whole, Baselga expressed excitement about the pace of discovery and the implications of recent findings.

“We now have the capacity to interpret much better what’s going on in the tumor and to adopt our therapies based on that,” he said. “This is powerful, and yes, I do believe that we are at a turning point.”

Baselga discussed his own research more extensively in this interview with OncologyLive.

OncologyLive: Is there a theme in these three studies?

Baselga: Yes, in the three cases we have combined new, targeted therapies to whatever was the standard of care. That’s the theme—trying to look for synergistic interactions with targeted therapeutics in breast cancer.

What are the challenges of investigating combination therapies?

Perhaps the most important one is trying to design a clinical trial that will be able to answer the questions that you’re looking for in a way that is error-free and that has good, strong support. It requires a lot of time and efort to do the right and appropriate clinical trial design, and you have to base that on your laboratory data or on data from earlier studies. Trying to model in the clinic what has happened in the lab—that’s the most challenging part of all.

The second challenge is in the case of these newer, more avant-garde, if you wish, clinical trial designs such as NeoALTTO. The challenge there is to set up a whole new set of conditions. The concept of neoadjuvant therapy, and doing clinical trials with neoadjuvant therapy, is not an easy one. On top of that, you want the concept of having a window period of time in which you only administer anti-HER2 therapy without chemotherapy. That gives us yet another level of complexity.

So we need to get the buy-in from investigators and from the patients. You need pathologists to help. You need to build in very complex imaging. This is not easy, I can tell you that.

BOLERO-2*

N = 724

  • Postmenopausal estrogen receptorpositive
  • Unresectable locally advanced or metastatic breast cancer
  • Recurrence or progression after letrozole or anastrozole
 
 
n = 485
n = 239
Everolimus
+
Exemestane
Placebo
+
Exemestane
 
  Placebo
+exemestane
Everolimus
+exemestane
Progression-free survivala 3.2 mo 7.4 mo
Clinical benefit rateb 25.5% 50.5%
aLocally assessed.
bIncludes complete response, partial response, stable disease >6 months.
*Based on data presented at 2011 CTRC-AACR San Antonio Breast Cancer Symposium, Texas, December 6-10, 2011.

BOLERO-2

What is the mechanism of action of the combination therapy used in BOLERO-2?


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Cancer Summaries and Commentaries™: Update from Chicago: Advances in the Treatment of Breast CancerJul 31, 20181.0
Community Practice Connections™: Medical Crossfire®: Translating Lessons Learned with PARP Inhibition to the Treatment of Breast Cancer—Expert Exchanges on Novel Strategies to Personalize CareAug 29, 20181.5
Publication Bottom Border
Border Publication
x