RxPONDER: A Huge Victory for Our Patients

At SABCS yesterday, SWOG study lead Dr. Kevin Kalinsky delivered the key messages of the trial to date: Postmenopausal women with HR+, HER2- breast cancer involving one to three lymph nodes, and a recurrence score result of 25 or less, can safely skip chemotherapy – saving them the time, expense, and possibly toxicities that can be associated with chemo. At the same time, premenopausal women with the same presentation can be assured that chemo can, in fact, help them live longer or without their disease spreading.
 
An estimated 36,000 American women are diagnosed each year with HR+ HER2- breast cancer involving one to three nodes, and who would be expected to have a recurrence score result of 0-25 from an Oncotype DX genomic test. Worldwide, of course, this number is much larger.

This is high impact work – likely to change practice quickly – and that is why it landed a top slot on the SABCS program. The work is also a satisfying second chapter to TAILORx, whose results were announced at ASCO in 2018. Both RxPONDER and TAILORx studied women with HR+ HER2- breast cancer. The difference is that TAILORX looked at lower-risk patients, whose cancer did not involve lymph nodes. RxPONDER looked at women with a higher absolute risk for recurrence, i.e., with cancer in one to three lymph nodes.

At the third prespecified analysis, our data safety monitoring committee flagged the RxPONDER team about the clear pattern they were seeing in the data – the differential effect of chemotherapy benefit based on menopausal status. The study sponsor, the NCI, agreed to the early release to serve the best interest of patients.

You can get all the details about the study in our joint press release with the NCI here. I want to say RxPONDER is not only an important international breast cancer trial; it is, on many levels, a success story for the SWOG Cancer Research Network.

It builds on ground-breaking work in our breast committee, performed over 30 years by legends like Drs. Gabe Hortobagyi, Kathy Albain, Dan Hayes, Julie Gralow, Bill Barlow, and others on the use of the recurrence score as a tool to personalize breast cancer treatment. RxPONDER had its origins in findings from S8814, launched back in 1989 and led by Dr. Albain. In S8814, SWOG went back and analyzed the recurrence scores from tumor tissue in patients with lymph node positive HR+, HER2- breast cancer, demonstrating that higher recurrence scores – those greater than 30 – could predict chemotherapy benefit. Based on those results, SWOG investigators hypothesized that higher scores, even those in the lower score range of 0-25, might predict greater chemotherapy benefit. To answer the question, the SWOG breast committee launched RxPONDER in 2011.

Not only does the trial represent years of focused effort, it represents years of fruitful mentorship. Kevin Kalinsky took part in our Young Investigator Training Course in 2010 and has benefitted from unparalleled mentorship from Dr. Dawn Hershman and other world-class SWOG experts and colleagues in breast cancer research – many of whom were co-authors on the RxPONDER presentation. This guidance, and early career support by The Hope Foundation for Cancer Research, has paid off.

RxPONDER also proves the wisdom of public investments in cancer research, the value of investigations conducted over time, and the inspiring drive of the next generation of cancer leaders. We can also celebrate the delivery, yet again, on the promise of personalized medicine. We are moving away from a one-size-fits-all approach to cancer treatment to one that is more uniquely tailored to the people we see in our clinics each week.

My congratulations to the RxPONDER team and the SWOG breast committee, led by Drs. Lajos Pusztai and Priyanka Sharma. You’ve brought great distinction to all of us here at SWOG. More important, you have benefitted future patients immeasurably.