Gabriel Miller; Clifford Hudis, MD


June 26, 2014

In This Article

The 2014 annual meeting of the American Society of Clinical Oncology (ASCO), held May 30-June 3 in Chicago, featured a number of important studies that may affect how primary care physicians treat their patients.

Medscape asked Clifford Hudis, MD, ASCO's outgoing President and Chief of the Breast Cancer Medicine Service at Memorial Sloan Kettering Cancer Center in New York City, to provide takeaways on how these study results may influence primary care physicians' practice.

The first 4 studies were featured in the meeting's plenary session; the remaining were presented as oral abstracts on topics most likely to affect primary care: cancer screening and prevention, health services research, and caring for cancer survivors.

Plenary Sessions

Premenopausal Women With Hormone Receptor-Positive Early Breast Cancer

Results of abstract LBA1 showed that for premenopausal women with hormone-sensitive cancers, the aromatase inhibitor exemestane, when given with ovarian function suppression, more effectively prevents breast cancer recurrences than tamoxifen.

Tamoxifen has long been the gold standard for preventing breast cancer recurrences in premenopausal women. However, when both tamoxifen and exemestane were used in combination with treatments that suppress ovarian function, including the drug triptorelin, surgical oophorectomy, or ovarian irradiation, exemestane reduced the relative risk of developing a subsequent invasive cancer by 28% and specifically reduced the relative risk for breast cancer recurrence by 34%.

Because ovarian function suppression may affect future fertility, longer follow-up is needed to assess survival and any long-term side effects, including any effect on fertility, Olivia Pagani, MD, the study's lead author, said.

Clifford A. Hudis, MD: "The first abstract at the ASCO plenary session demonstrated that if you believe that menopause is a treatment for premenopausal women with breast cancer, then menopause and aromatase inhibitors are better still. This has consequences for the general audience because these are drugs that are used even for prevention right now. These are drugs with side effects that will lead to people calling their general doctors, saying, 'I'm achy.' It leads to the development of osteopenia and osteoporosis in some patients. I think these are important advances to understand. The take-home is that if you're made menopausal, then there is a small benefit to using an aromatase inhibitor rather than the old standby, which was tamoxifen.

"There's a related abstract not in the plenary session, by Halle Moore, MD. It has to do with the use of ovarian suppression not as treatment for cancer, which is what I was just talking about, but instead as a way of protecting the ovaries and maintaining fertility, and this has repercussions for all young women treated for curable cancer, probably well beyond breast cancer.

"In this case, they took women with triple-negative breast cancers -- that is, cancers that were not responsive nominally to hormones -- and they randomized them to have their ovaries temporarily shut down with chemical treatment or not. About 2 years later, they looked at how many were menstruating again, and they looked at blood tests that would indicate being fertile or not, and finally, they also recorded pregnancies. On all of the scores there seemed to be a substantial improvement in the maintenance of fertility, and indeed, there were more pregnancies in the women who had this approach.

"This is something that I think will have repercussions potentially in the long run far beyond just breast cancer, far beyond the group that was studied; and again, it's something that general internists and others should know. There was no negative for it in terms of the cancers they were treating, so if there is a real chance that it preserves fertility, this is a long-term survivorship issue that I think warrants attention."

Earlier Chemotherapy for Prostate Cancer

Abstract LBA2 suggested that adding the chemotherapy drug docetaxel to standard hormone therapy increases survival for men with hormone-sensitive prostate cancer. The effect was most pronounced in men with extensive disease.

After 29 months of follow-up, men given only standard hormone therapy had a median overall survival of 44 months, while those given hormone therapy plus chemotherapy had a median overall survival of 57.6 months.

The study's lead author, Christopher Sweeney, MBBS, said the study was the first ever to identify a strategy that prolongs survival in newly diagnosed metastatic prostate cancer and that the overall results suggest "one of the biggest improvements in survival we have seen in a trial involving patients with an adult, metastatic solid tumor."

Dr. Hudis: "This really can be, for a non-oncology audience, summarized simply. For very advanced prostate cancer that can't be cured, combining hormone therapy with chemotherapy was better than hormone therapy alone. This is, from a principal point of view, a little different from our usual approach, which is to give as little therapy as we need to for as long as possible. This says that it's worth a little bit of upfront toxicity, because there is a trade-off with a longer survival stretching about a year and a half. That's a big delta, so that's something that would change how we think about men with incurable prostate cancer."

Long-term Progress Against Colon Cancer

In a study of patients with metastatic colorectal cancer, abstract LBA3 demonstrated that both bevacizumab and cetuximab, when combined with a standard chemotherapy regimen, are appropriate for first-line treatment.

Overall survival in both groups of patients was between 29 and 30 months; progression-free survival was between 10 and 11 months.

Dr. Hudis: "[This trial] showed no difference between 2 different targeted approaches for colon cancer. I won't get into the specifics of them because that is for an oncology audience, but there was a silver lining that needs to be noted, and that is that the median survival for people with incurable metastatic colon cancer was 29 months in this study. Half of the patients diagnosed with metastases are alive for 2.5 years approximately or just about that. Of course, half live longer than that. This is a very different world from 10 or 15 years ago and it does reflect the fact that we've got a treatable, if incurable, disease. It is not that all bets are lost when somebody develops metastatic disease. We can help them."

Disappointing Results for HER2 Breast Cancer Treatment

Adding a second targeted therapy, lapatinib, after surgery is not more effective in the treatment of HER2-positive breast cancer than using trastuzumab alone, abstract LBA4 showed.

The trial overturned results of a much smaller previous study suggesting that a second targeted therapy improved patients' response to treatment.

The design tested trastuzumab alone, lapatinib and trastuzumab concurrently, and lapatinib and trastuzumab given sequentially. At 4 years, the rate of breast cancer-free patients was 86%, 88%, and 87%, respectively.

Dr. Hudis: "The simple idea here is that we give drugs after surgery in breast cancer just to prevent distant metastases from growing out. For the non-oncologists, the real simple bottom line is, some people have micro-metastatic disease that you can't detect at the time of surgery. The drugs we give after surgery, be it hormones like tamoxifen or chemotherapy, they're not really given for superstitious reasons. They're given to treat undiscovered 'mets,' or metastatic disease. These studies have become very large as patients have done better and better. It's inefficient and expensive. There is a movement right now to use models of response in the preoperative setting to predict long-term outcomes.

"Let me be very clear: The prima facie evidence is that if you shrink the cancer in the breast and then operate, then you would have a good hint about whether that treatment was effective against micro-metastases. So, instead of a 5000- or 8000-patient adjuvant trial where many patients were going to do well anyway, you can enroll a few hundred patients, and if you see that your new drug is active, then you have a much better idea about how much it might contribute to long-term outcomes. We knew for one of the targeted HER2 therapies, lapatinib, that in some studies it was a significant addition to existing treatment. Many people were optimistic that it would improve the overall outcomes in the adjuvant setting.

"[This study at ASCO] was notable because it was negative. It was negative for complex reasons, arguably: toxicity -- the fact that the patients overall did very well. But it does represent a challenge to the general idea that you can leave the cancer in the breast, give a drug, assess its benefit, and accurately predict the long-term outcomes. It shows that we have more work to do in that area.

"This matters for the general internists and others who may be hearing about the use of preoperative therapy as a routine in their communities. Outside of clinical trials, it's not clear that a patient who has a curable and operable breast cancer necessarily benefits from getting their treatment preoperatively. The general internists should be aware that that is, let's say, unsettled science at the moment."


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