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OncOlOgy Times The Independent

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November 10, 2012 ] Vol. 34 ] No. 21[ News ] Analysis ] Commentary ] Controversy ]

Publishing for

34 Years

oncology-times.com

[ A L S O ] SHOP TALK � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �5

Lymphedema’s Emotional Challenges � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 9

Breast Cancer: New Data for Calculating Cardiotoxicity Risk � � � � � � � � � � � � � � � � � � � � � � � � � � � �22

JOE SIMONE: Pogo and American Health Care � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �28

GEORGE SLEDGE: On Cross Training� � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �30

Esophageal Cancer: Gefitinib Second-Line Therapy for Select Patients � � � � � � � � � � � � � � � � � � � � �31

BOOKS: ‘Planned Bullyhood’� � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � �34

How Health IT is Changing the Practice of Oncology: Clinical Decision Support � � � � � � � � � � � �35

@OncologyTimes Facebook.com/ OncologyTimesNews

Controlling Spiraling Costs of Cancer Called Moral Imperative

BY PEGGY EASTMAN

Holding down costs is both a professional and moral responsibility, said

speakers at an Institute of Medicine National Cancer Policy Forum meeting

on delivering affordable cancer care while improving quality�

Page 18

Best Practices & Teamwork Help Reduce Pediatric Central Line Infections p.24

Free Instant Access to OT on Your iPad!

Breast Cancer Symposium: Predictive Updates pp.20, 23

The Survivorship Care Gap: Psychosocial Care—Making It the Standard p.10

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SAN FRANCISCO—Women with triple-negative breast cancer (HER2-negative, progesterone-receptor-negative, and estrogen-

receptor negative) who have a complete pathological response after neoadjuvant chemotherapy have a better prognosis than those who have residual disease after treat-ment� Until now, however, investigators have not examined whether all residual disease is equal�

In a new study reported here at the Breast Cancer Symposium (Abstract 106), German researchers found that women with small residual disease (i�e�, classified as ypT1-2) after neoadjuvant chemotherapy had significantly better overall survival and disease-free survival rates two years after surgery than women with larger- volume residual disease (ypT3-4)�

“The practical implication of this study is that those who are in the ypT3-4 group after neoadjuvant treat-ment absolutely need post-neoadjuvant treatment,” said the study’s first author, Peter Kern, MD, Associate Senior Consultant at the University Hospital of Essen Comprehensive Cancer Center� “On the other hand, we can now reas-sure the women who are in the ypT1-2 group�”

The researchers analyzed data from 3,758 patients with triple-negative breast cancer who were treated at the West German Breast Center in Essen or an af-filiated hospital between 2009 and 2011� Of those, 506 patients had residual dis-ease after neoadjuvant chemotherapy: 221 women had ypT1 disease, 138 had ypT2

disease, 97 ypT3 disease, and 73 ypT4 disease�

When the investigators plotted clini-cal outcomes by residual tumor size, they saw that the ypT1-2 patients and ypT3-4 naturally separated, Kern told OT� Of the women in the ypT1-2 group, 66�5 percent were disease-free at two years, compared with 22�8 percent of patients with ypT3-4 disease� “This is absolutely a disaster,” he said, regarding the ypT3-4 group�

Women with smaller-volume residual disease also had longer overall survival� Specifically, 79 percent of women in the ypT1-2 group remained alive at two years, compared with 60 percent of women with ypT3 and 68 percent of women with ypT4 disease�

He noted that until now, research-ers looked at pathological response in a dichotomous way—either a complete re-sponse or a non-complete response� And there were just two survival curves—one for each of those response groups— published by Cornelia Liedtke et al in the Journal of Clinical Oncology in 2008 (26:1275-1281)� (Liedtke is also a co-author on the current study�)

“I always wondered if it was black and white,” Kern said� “If you have a patient whose residual tumor is 3�5 cm after che-motherapy; you have another patient, with residual tumor of 8 mm—they both have the same fate, according to the Liedtke et al paper, which is one of the most cited publications, in oncology�”

Based on his analysis though, he is clear that size does matter, he said�

DiscussantThe size of the study population was un-usually large for a triple-negative cohort and that was a strength of the study, according to Melinda Telli, MD, Assistant Professor of Medical Oncology at Stanford University, who talked about the work during a poster discussion session� On the other hand, she said, two years was a

relatively short follow-up, even for women with this type of breast cancer� Moreover, she said, Kern and colleagues did not include other prognostic factors in their analysis, which would have strengthened the work�

“In my research and clinical practice, I find this residual cancer burden index particularly helpful when thinking about prognosis for patients who have residual disease after primary chemotherapy,” Telli said, referring to a slide showing the re-sidual disease burden calculator on the MD Anderson Cancer Center website� “This was an index developed by Fraser Symmans and colleagues, which set out to try to stratify responses beyond pCR and non-pCR�”

The risk calculator takes into account primary tumor bed size, overall percent cellularity, percentage of disease that is in situ, the number of positive nodes, and the diameter of the largest axillary metastasis� Based on those features, the calculator places each patient into one of four risk categories, from RCB-0, which is equiva-lent to pathological complete response, to RCB-III, which is extensive residual disease�

The calculator holds up for triple-neg-ative disease, Telli said, and provides good separation between disease-free survival curves for the four risk groups�

To illustrate the point, she showed an example from her own practice� The patient initially presented with a T3 tumor, over 8 cm in size� The patient had a clinically complete response to neoadjuvant chemotherapy, but the

Triple-Negative Breast Cancer: Residual Disease Volume Correlates with OutcomeBY RABIYA S. TUMA, PHD

Until now, researchers have tended to look

at pathological response in a dichotomous

way—either a complete response or a non-complete

response.

Women with small residual disease

after neoadjuvant chemotherapy had

significantly better overall survival and

disease-free survival two years after

surgery than women with larger-volume

residual disease.

PETER KERN, MD: “The practical implication of this study is that those who are in the ypT3-4 group after neoadjuvant treatment absolutely need post-neoadjuvant treatment. On the other hand, we can now reassure the women who are in the ypT1-2 group.”

MELINDA TELLI, MD: “The point that needs to be made is that in this study, the patients with RCB-I, minimal residual disease, do have the same favorable prognosis as those who have an RCB of 0, complete pathological response. Size does matter, but so do other factors, including percent cellularity and nodal status.” continued on page 22

The meeting is co-sponsored by the American Society of Breast Disease, American Society of Breast Surgeons, American Society of Clinical Oncology, American Society for Radiation Oncology, National Consortium of Breast Centers, and Society of Surgical Oncology.

6 Co-sponsors

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post-surgery pathology report indicated that she still had T3 disease, with a 5 cm tumor remaining� When Telli requested a second pathology review, the patholo-gist reported that most of the tumor bed was scar tissue with only one percent cel-lularity� Putting that information into

the risk calculator, the patient was put into the low-risk category with minimal residual disease, RCB-I�

“I think the point that needs to be made is that in this study, the patients with RCB-I, minimal residual disease, do have the same favorable prognosis as those who

have an RCB of 0 [complete pathological response],” she said�

“I think size does matter, but so do other factors, including percent cellularity and nodal status,” she concluded� “I think these do need to be considered when thinking about prognosis in these patients�” O

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➞TRIPLE-NEGATIVEcontinued from page 20

Better models to predict cardiac damage from adjuvant trastu-zumab after an anthracycline-based therapy in HER2-positive

breast cancer have been generated by seven-year follow-up from the National Surgical Adjuvant Breast and Bowel Project B-31 trial� These data, now avail-able online ahead of print in the Journal of Clinical Oncology (doi: 10.1200/JCO.2011.40.0010), show that:

• late cardiac events are uncommon;• impaired left ventricular function

at least partially recovers in many patients after trastuzumab is stopped; and

• the risk of cardiac events appears concentrated in identifiable subgroups, particularly those who already have a low normal left ventricular ejection fraction (LVEF), women who are older than age 50, and women with hypertension�

These findings provide at least some guidance for calculating a risk-to-benefit ra-tio for trastuzumab after an anthracycline-based regimen in women with primary HER2-positive breast cancer, the research-ers said� Based on the findings, they created an equation with which to derive a Cardiac Risk Score in patients who are candidates to receive trastuzumab therapy�

The study’s lead author, Edward H� Romond, MD, Professor in the Division of Medical Oncology at the University of Kentucky, cautioned, though, that the score was created in the context of eligibil-ity to the trial�

“We hope that within these parameters the model may prove useful for assessing many, but not all, patients, but the impor-tant point to remember is that, regardless of the choice of chemotherapy regimen, cardiac monitoring is integral to the use of trastuzumab,” he said�

In patients the decision to use trastu-zumab with or without previous exposure to an anthracycline “is not black or white,” he said� “Outside of a clinical trial, the decision about the appropriate choice of adjuvant therapy should take into account several considerations including the degree of risk from the cancer, the risk of cardiac toxicity from the treatment regimen, and other co-morbidities of the patient�”

The initial 27-month cardiac safety data from this 1,830-patient randomized study, published in 2005 (Tan-Chiu et al: JCO 2005;23:7811-7819), showed that

adjunctive trastuzumab plus paclitaxel af-ter a four-cycle course of doxorubicin and cyclophosphamide was associated with a “modest but significant” increase in cardiac events (mostly symptomatic congestive heart failure) compared with use of adju-vant paclitaxel alone (4�1% vs� 0�8%)� The relative rates of cardiac events after seven years, reflecting the recovery of cardiac function after trastuzumab was stopped, were almost unchanged (4% vs� 1�3%), the researchers reported�

The recovery of left ventricular function was shown both clinically and by follow-up multiple-gated acquisition (MUGA) scans� Specifically, of 37 evaluable patients in the trastuzumab group with a cardiac event, 33 had no symptoms six months after stopping trastuzumab� And although one patient in this group did die of con-gestive heart failure during the course of treatment, the follow-up MUGA scans demonstrated that LVEF had climbed above 50 percent in 21 patients�

It is notable that there was also one such death in the patients who did not receive trastuzumab, Romond said� Of 69 trastu-zumab patients with asymptomatic LVEF less than 50 percent for whom there are data, 51 had LVEF higher than 50 percent six months after stopping trastuzumab�

It is well known, he noted, that the cardiac safety of trastuzumab, particularly when administered after exposure to an anthracycline, has been a cause of concern with the use of this agent in the treatment of patients with primary HER2-positive breast cancers� And despite abundant evidence that adjuvant trastuzumab, par-ticularly after anthracycline-based chemo-therapy, substantially reduces the risk of recurrence, the cardiac toxicity has created uncertainty about the risk-to-benefit ratio�

Accompanying EditorialWriting in an accompanying editorial (DOI:10.1200/JCO.2012.44.9611), Erica L� Mayer, MD, MPH, and Nancy U� Lin, MD, both of Dana-Farber Cancer Institute, said that use of anthracycline-based trastuzumab regi-mens in HER2-positive breast malignan-cies has declined “precipitously” over the past several years, a likely reflection of this uncertainty�

Asked to comment on the clinical sig-nificance of the new B-31 data, Mayer said she hoped the safety information will help clinicians and patients reconsider the use of anthracycline-containing regimens, particularly in patients with a moderate-to-high risk of relapse�

And, based on the findings indicating that the risks of clinically significant car-diac toxicity are “quite low for many pa-tients,” the goal now is to develop methods with which to calculate a clinically viable risk-to-benefit ratio, she said�

The scoring system proposed by the B-31 investigators was derived from a regres-sion analysis that found that only age and baseline LVEF were significant predictors of a cardiac event� When age younger than 50 was used as the index for comparison, the hazard ratio for having a cardiac event among patients age 50 to 59 was 2�43 and climbed to 2�73 for those 60 and older�

The hazard ratio climbed to 6�72 in those with LVEF that was 50 to 54 per-cent compared with those with LVEF of 65 percent or higher� The equation pro-ducing the score on the basis of these risk factors indicated that the risk of a cardiac event is concentrated in older patients with low normal LVEF although other factors may be important in individual patients, the researchers said�

Breast Cancer: Long-Term Data from Trastuzumab Trial Give Guidance for Calculating Cardiotoxicity RiskBY TED BOSWORTH

“There is a lot of caution in this

area because the first principle of

medicine is to do no harm, but there is no doubt that the

protection provided by trastuzumab

against recurrence is substantial.”

EDWARD H. ROMOND, MD: “We hope that within the parameters the model may prove useful for assessing many patients, but the important point to remember is that, regardless of the choice of chemotherapy regimen, cardiac monitoring is integral to the use of trastuzumab.”

continued on page 23