Adjuvant RCC Therapy Remains a Challenge as Treatment Landscape Continues to Evolve

Nancy Moldawer, RN, MSN

The ultimate goal in oncology should be to cure patients of their cancer, not merely extending their progression-free survival (PFS), and for this reason, more studies in the adjuvant setting for renal cell carcinoma (RCC) are necessary, according to Nancy Moldawer, RN, MSN. Moreover, although there have been 3 negative trials in the neoadjuvant and adjuvant setting of RCC—CheckMate-914 (NCT03138512), IMmotion010 (NCT03024996), and PROSPER (NCT03055013)––investigators continue to seek out new modalities which encompass broader patient populations, suggesting that the quality of care is continuing to improve.

“The one thing about the landscape of kidney cancer for oncology nurses is that it is always changing,” Moldawer said. “Nurses who care for these patients need to understand the current data and use evidence-based treatment protocols in their practice so they can be in the forefront, and provide patients with the best care, [and] side effect management, so they can continue on their therapies, for as long as possible.

Moldawer is the cochair of the Kidney Cancer Associations’ Clinical Advisory Board and works at Cedars Sinai Medical Center as a lead research nurse, where she oversees the clinical research activities for patients with kidney cancer in the Urologic Oncology Program.

In an interview with Oncology Nursing News®, Moldawer discussed what nurses should know about how recent data may affect treatment decisions for patients.

Oncology Nursing News®: The results from the combination arm of CheckMate-914 were ultimately negative but a large percentage of patients did not complete the intended 6 months of therapy. Similarly, negative results were observed with adjuvant atezolizumab (Tecentriq) in IMmotion010 and neoadjuvant nivolumab (Opdivo) in PROSPER. How do you interpret these findings, and what might the next steps be for neoadjuvant and adjuvant therapy in high-risk RCC?

Moldawer: There’s a difference when treatment is given as adjuvant therapy vs therapy for patients who have metastatic disease. It’s a challenge either way, but in the adjuvant population, it takes a bit more time for patients to understand the goals of therapy at a time when there is no evidence that cancer is present. They are on the cusp of recovering from a major oncologic surgery and then need to think about and plan for a therapy when they’re just returning to their baseline activities. [Patients] recuperate at different times, so I’m not saying that these patients are 100% ready to embark on treatment.

It’s difficult to deliver adjuvant care to patients because they feel OK. They’re taking a really big step [with] adjuvant therapy when we don’t know whether it’s going to help and in some cases if they really need it. Earlier adjuvant studies, from 5 to 10 years ago, found that as well. Patients stopped treatment early, [saying,] “Oh, I can’t bother with this, I need to get back to feeling better, and we don’t know what the results [with this treatment] are going to be... I am going to terminate because these are really tough AEs [adverse events].”

Adjuvant therapy has difficult AEs and was oriented to an oral pill daily dosing schedule. It was chronic administration of a pill every day for these patients for about one year. That was difficult to do. Instead of feeling better, they continued to feel worse and worse from the side effects.

The COSMIC-313 trial (NCT03937219) showed a significant improvement in PFS with cabozantinib (Cabometyx) plus nivolumab and ipilimumab (Yervoy) vs the immunotherapy combination alone in advanced, untreated RCC. What is the significance of the control arm? Can you explain what the ramifications of this study are on the frontline landscape?

For those of us who had been working with patients [with kidney cancer] in clinical trials, the significance of that control arm was it became the new standard of care and witnessed a combination immunotherapy as the comparator arm. That alone is really exciting. It’s an advancement for us in that clinical arena— getting away from other standard of care arms [such as single-agent] sunitinib [Sutent]. That’s the most significant thing. We now have a combination immunotherapy control arm, and this was the first time it was used in a clinical trial.

What does this mean in terms of frontline therapy? Well, a lot of things. However, first and foremost, the study doesn’t tell us today that it’s ready for standard of care. It’s a bit too early to say this is going to be our new standard. We need to let the data mature more and understand the adverse event (AE) profile and quality of life

There are many frontline combination therapies for advanced kidney cancer. One of the first questions that we’re always asked is: How do you decide what treatment for your patient? If you only look at the literature and go by the results, you may select one because it is the best. But it doesn’t always apply to the patient in your office sitting as you discuss treatment options.

What are their comorbid diseases? Other factors to consider are age, symptoms from the cancer and what they want from therapy. With immunotherapy, we’re always concerned about baseline endocrine abnormalities that the patient might have and giving them immunotherapy could make their comorbid disease even worse.

From this [COSMIC-313], it’s going to be a lot of discerning which patients can receive this therapy, because of the high number of AEs associated with it. You have to be really careful and find the right patient that we think we can safely give this particular combination to.

In non–clear cell RCC, based on the results of the KEYNOTE-B61 trial (NCT04704219) with pembrolizumab (Keytruda) and lenvatinib (Lenvima), could combinations redefine the frontline landscape in this population as in the clear cell population?

I certainly would like to say yes. Combination therapies will help many patients with non-clear cell carcinoma. I can’t tell you how many patients I’ve seen, how many meetings I’ve been at, and how many patients support groups that I’ve attended where I have heard, what about the patients with non-clear cell disease?

I’m cautiously excited to say [that] maybe we have some treatments right in our own backyard that we’ve used for clear cell, and now we feel that perhaps they might be able to translate to the non-clear cell population. We are hopeful about that and we certainly use these combinations for our non-clear cell patients. [Additionally,] we’re happy to say that we have some data that supports what we do for our [patients with] non-clear cell disease rather than saying, “Let's give this a try.”

It's a win-win for the patient and for the physician caring for them, that we have some interesting data moving forward to treat this [population]. We did not have to look for novel type of therapies. We already had them in our basket, so to speak.

In your opinion, what should oncology nurses know about the current landscape of RCC? Do any of these recently presented data indicate that caring for patients with kidney cancer will change soon?

Nurses caring for [patients with] kidney cancer need to be educated on the results of the adjuvant trials and the newer first line studies. There have been a decade of adjuvant trials and the majority of the [results] have been negative. We have 2 positive studies. Hence, we need to have very careful conversations about therapy with patients after they’ve had their nephrectomy. In our practice, we see patients prior to their surgery and after, and a question that they have is: What can I do to prevent this cancer from ever coming back?

The one thing that we often forget in oncology with adjuvant studies that is that the goal is to prevent the cancer from coming back, not just extending the time of a possible recurrence. Our goal is to have treatment regimens that will get rid of any residual cancer that might be around. Having those conversations with the patient is important.

Moving forward, we still need to have more clinical trials in this space so that we can come up with the homerun for these patients.