EXPERT POINT OF VIEW: Eric P. Winer, MD, FASCO; Heikki Joensuu, MD; and Julie Gralow, MD, FASCO

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IN INTERVIEWS with The ASCO Post and in discussions held during the meeting, several breast cancer experts weighed in on the findings of GeparSepto and CALGB 40502. 

Eric P. Winer, MD, FASCO

Eric P. Winer, MD, FASCO

Eric P. Winer, MD, FASCO, Chief of the Division of Women’s Cancers and the Thompson Senior Investigator in Breast Cancer Research at Dana-Farber Cancer Institute, Boston, concluded that the findings are provocative but not practice-changing. 

For GeparSepto’s primary endpoint—pathologic complete response—a 9% absolute improvement was seen with neoadjuvant nab-paclitaxel over paclitaxel. “The interesting finding was that patients with triple-negative disease got the biggest bump,” he said, with pathologic response rates 22% higher with nab-paclitaxel; this magnitude of improvement was not observed in other subtypes. 

In the analysis of long-term outcomes, “somewhat to my surprise,” he offered, “there appeared to be an improvement in disease-free survival that was statistically significant.” The absolute improvement for nab-paclitaxel vs paclitaxel was 6.4% at 3 years and 7.3% at 4 years. Again, the subtype with the greatest benefit was triple-negative disease, where approximately 10% more patients on nab-paclitaxel were disease-free. The benefit was “only slightly less” in patients with hormone receptor–positive/HER2-negative disease, and, of interest, larger benefits were seen in patients whose tumors had low Ki67 levels and those not achieving a pathologic complete response. 

“In truth, I am not entirely sure what to do with these data, but they are intriguing enough not to ignore,” Dr. Winer maintained. 

In the metastatic setting, for the overall population of CALGB 40502, “paclitaxel seems to be the winner,” he said. By subtype, nab-paclitaxel was more effective in triple-negative disease and paclitaxel remained superior in hormone receptor–positive disease. 

“We don’t know what to make of this,” he continued. “Tests for the interaction of drugs by arm were statistically significant…. However, in terms of adverse events, there is absolutely no question that nab-paclitaxel is the more toxic of the two taxanes, with greater neuropathy and more frequent neutropenia.” 

In the CALGB 40502 post hoc subset analysis, in hormone-receptor–positive patients, paclitaxel appeared superior and nab-paclitaxel inferior, though in triple-negative disease there was a suggestion that both progression-free and overall survival were improved with nab-paclitaxel. Toxicity, discontinuation of therapy, and dose reductions were more frequent with nab-paclitaxel. 

Heikki Joensuu, MD

Heikki Joensuu, MD

For Heikki Joensuu, MD, Professor of Oncology at the University of Helsinki in Finland, “The issue is still open.” He told The ASCO Post that he would like to see more evidence; meanwhile, “I would view the two taxanes as equal drugs in standard practice, though paclitaxel has less neuropathy and is more economical.” He concluded, “I would say that, after today, nab-paclitaxel is abreast with paclitaxel, but in my mind, at this point in time, it’s not a clear winner.” 

Positioning the Drugs in Practice 

“WHEN I BRING these two studies together,” Dr. Winer concluded, “I think that in the metastatic setting, nab-paclitaxel is clearly a more toxic drug, and even though it was mildly superior in triple-negative disease in this post hoc analysis, the differences in absolute terms are really quite modest. Apart from patients who are intolerant of paclitaxel for one reason or another, I would probably continue to use paclitaxel in that setting.” 

He further concluded, “In the adjuvant and neoadjuvant settings, it’s hard to ignore the GeparSepto data. It needs further study, but for the time being, I personally would not use nab-paclitaxel in either of those settings outside of a clinical trial.” 

Julie Gralow, MD, FASCO

Julie Gralow, MD, FASCO

Julie Gralow, MD, FASCO, Director of Breast Medical Oncology for the Seattle Cancer Alliance, said despite the somewhat disparate findings between the studies, she does not believe nab-paclitaxel works better in one setting than another. And while nab-paclitaxel offers some advantages, she still finds little use for it in her practice. 

“It would be different if the cost were the same, but it’s much more expensive than paclitaxel,” she said, “and its use is limited by my payers.” 

“The metastatic trial [CALGB 40502] is pretty definitive in terms of paclitaxel being the best choice, so unless I have a patient who has an infusion reaction or can’t take steroids, it makes sense to stay with paclitaxel. Plus, my payers won’t allow nab-paclitaxel in this setting,” Dr. Gralow offered. “In the preoperative setting, you do see somewhat higher pathologic complete response rates with nab-paclitaxel, but I’m not convinced I need to use it here either.” ■

DISCLOSURE: Drs. Winer and Joensuu reported no conflicts of interest. Dr. Gralow has been a consultant for Genentech/Roche, Novartis, Merck, Pfizer, Sandoz, Puma, and AstraZeneca. 

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