Virginia Kaklamani, MD

For several breast cancer experts interviewed by The ASCO Post, the phase III oral paclitaxel study and the drug itself had some limitations. Virginia Kaklamani, MD, of UT Health San Antonio, moderator of a press briefing, thought that the dosing process and the 11 pills or so per day was a “limitation” for oral paclitaxel but added, “Keep in mind it’s only 3 days per week, not every single day.” She also noted that the oral drug was compared to a 3-weekly dose of IV paclitaxel, which is no longer the standard. “There are several other trials that show the weekly [IV] dose of paclitaxel is more efficacious,” she said.

Study Design Concerns

Steven E. Vogl, MD, of the Bronx, New York, told The ASCO Post that whether a drug is oral or IV is not an issue with him, “but I am very interested if neurotoxicity is reduced.” Dr. Vogl wondered if the administration schedule would be cumbersome to patients (11-hour fasts on 3 successive days per week). He was also concerned about the use of a modified intent-to-treat analysis as the primary endpoint, explaining that this excludes patients from the analysis “who did not do well on the experimental treatment because they did not get enough of it.”

Steven E. Vogl, MD

He added, “You are guaranteeing that you won’t have early failures on the experimental arm,” noting that Richard Gelber, PhD (Professor, Biostatistics and Computational Biology, Dana-Farber Cancer Institute), calls this “guarantee-time bias.” “This makes the experimental treatment look better because you are requiring patients to be alive and taking the drug [given for 3 days per week] 3 weeks later, which is not required of the IV paclitaxel patients [who finish 3 weeks of therapy on the first day].”

This process can also affect response rates, since patients whose cancer worsens in the first 3 weeks of oral paclitaxel therapy are removed from the denominator for total patients treated, he said, attributing this observation to Alan Coates, AM, FRACP (statistician and medical oncologist, The University of Sydney), who also heard the data.

Patient Perspective

Gary Lyman, MD, MPH, Professor of Medicine and Director, Health Services and Outcomes Research in Medical Oncology at Duke Comprehensive Cancer Center, Durham, North Carolina, echoed concerns about the “complicated” regimen that could impact a patient’s “normal day.” “I suspect a lot of patients won’t be thrilled with that, even though it’s an oral medication. They need patients to weigh in on this issue,” he suggested.

Gary Lyman, MD, MPH

Ginny Mason, BSN

One patient who did weigh in on the study at the meeting was Ginny Mason, BSN, of the Inflammatory Breast Cancer Research Organization in Indiana, a breast cancer survivor herself. “Patients would probably stand on their head in the corner and take the pills if it allowed them to do the things they need to do,” she said. “If I could make the choice for something that produces less neuropathy, I would do it.”

She pointed out that many women with metastatic breast cancer want to avoid the infusion center—a source of anxiety for them—at all costs, and she predicted the manufacturer will find an easier way to dose the drug. Meanwhile, she added, “Most of us with cancer take a handful of pills all the time anyway.” ■

DISCLOSURE: Dr. Kaklamani has received honoraria from Celgene, Eisai, Genentech, Genomic Health, Novartis, Pfizer, and Puma Biotechnology; has served in a consulting or advisory role for Amgen, AstraZeneca, Athenex, Celldex, Eisai, and Puma Biotechnology; has participated in a speakers’ bureau for Celgene, Eisai, Genentech, Genomic Health, Novartis, Pfizer, and Puma Biotechnology; and has received research funding from Eisai. Dr. Vogl and Dr. Lyman reported no conflicts of interest.