At ASCO, Noninferiority Trials Dominate, Prove 'Less Can Be More'

David L. Graham, MD


June 13, 2018

This year's annual meeting of the American Society of Clinical Oncology (ASCO), which closed last week, was replete with truly practice-changing presentations. The idea that "less can be more" in cancer therapy was one of the most common themes that emerged from the meeting, and several presentations highlighted this approach.

Two important presentations were in the field of breast cancer therapy. The TAILORx trial,[1] which looked at the use of OncotypeDX risk scores in women with node-negative, hormone receptor–positive, HER2-unamplified breast cancer, was presented in the plenary session. Our previous understanding was that women with low-risk scores—that is to say, lower than 10—were the only group that could be adequately treated with hormone therapy alone and could avoid cytotoxic chemotherapy. In this noninferiority trial involving more than 10,000 women, patients with recurrence scores of 11-25 were found to do just as well with endocrine therapy alone as those with chemotherapy plus endocrine therapy. One caveat is that women under the age of 50, evaluated in a subgroup analysis, did not have the same level of benefit as women over the age of 50.

Another noninferiority trial, PERSEPHONE, studied more than 4000 women with HER2-amplified breast cancer.[2] The investigators found that 6 months of trastuzumab was as effective as 12 months of the same therapy. This was also associated with a significant reduction in cardiotoxicity in the women receiving 6 months of therapy. Given that approximately 17% of breast cancers are HER2 amplified, the potential impact of these results cannot be understated.

The CARMENA trial is the final example demonstrating that "less is more."[3] For many years there has been discussion about removing the primary tumor in patients with metastatic renal carcinoma. In the days when interferon was the only known therapy, some benefits of cytoreductive nephrectomy (CN) were reported. Now that more effective targeted therapies, such as sunitinib, are available, the question needed to be reassessed.

The CARMENA trial was a prospective, randomized trial of CN followed by sunitinib versus sunitinib alone, also designed as a noninferiority trial. Compliance with the assigned therapy was not optimal; some patients did not get nephrectomy who were assigned to it, and some patients received "secondary nephrectomy" who were in the sunitinib-arm alone. In the intention-to-treat analysis, however, noninferiority was proven. Some discussants were concerned that the transition of immunotherapy to front-line treatment may raise further questions in the future, but sunitinib still seems to be the prevalent choice for metastatic renal cell carcinoma in the front-line setting. Whatever questions were raised, the clear consensus was that metastatic renal cell carcinoma should be evaluated in a multidisciplinary fashion before any treatment decision is made.

The history of cancer therapy has been to find an effective therapy and then tweak the regimen to give the least amount of therapy possible while still maintaining efficacy. While many presentations focused on personalized therapies, the most important presentations at ASCO 2018 truly demonstrated that less can be more.

For all of Medscape's coverage of the ASCO 2018 annual meeting, visit our ASCO 2018 conference page.