Naomi Haas, MD

Naomi B. Haas, MD, director of the kidney and prostate cancer program at Penn Medicine and professor of medicine at the Hospital of the University of Pennsylvania, discusses the choice of frontline treatment for favorable-risk patients with advanced clear cell renal cell carcinoma (RCC).

According to Haas, the 3 approved frontline tyrosine kinase inhibitor/immune checkpoint inhibitor combinations were superior to sunitinib (Sutent) in favorable-risk patients but none of the 3 stood out as the best option in terms of patient outcomes. The choice of regimen can come down to other factors such as the different adverse event (AE) profiles and the patients’ ability to tolerate therapy. Additionally, she says she might use cabozantinib (Cabometyx) plus nivolumab (Opdivo) in a patient with bone metastases since it has activity against the 

 pathway, which tends to have better outcomes for bone metastases.

Cabozantinib plus nivolumab or lenvatinib (Lenvima) plus pembrolizumab (Keytruda) could also be more appropriate than axitinib (Inlyta) plus pembrolizumab in patients who have high disease burden since these regimens were shown in trials to be better at providing rapid and deep responses.

 The cabozantinib/nivolumab, the axitinib/pembrolizumab and the lenvatinib/pembrolizumab patients all did well with favorable-risk disease but compared [with] a single-agent tyrosine kinase inhibitors such as sunitinib, which was the comparator arm, there wasn't a huge difference in how they did. Some of it is tailored to [AEs]. For example, if a patient develops bony metastases, and they're in the favorable-risk category, I might use cabozantinib/nivolumab a little bit more often than lenvatinib/pembrolizumab or axitinib/pembrolizumab, just based on the 

 activity that is seen in cabozantinib, and how 

 mutations may work a little bit better in patients with bone metastases, or MET-directed therapy, I should say.

If they have a very high burden of disease, and I need shrinkage and I need shrinkage quickly, I would use either nivolumab and cabozantinib or I would use lenvatinib with pembrolizumab because those 2 [regimens] had a pretty decent depth of response and did well in those categories.

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Naomi B. Haas, MD, discusses the choice of frontline treatment for favorable-risk patients with advanced clear cell renal cell carcinoma. 

Factors Influencing Frontline Therapy Options for Favorable-Risk RCC

Naomi B. Haas, MD, director of the kidney and prostate cancer program at Penn Medicine and professor of medicine at the Hospital of the University of Pennsylvania, discusses how patient characteristics and preference influence the choice of frontline treatment for advanced clear cell renal cell carcinoma (RCC).

There are 4 regimens that are preferred by National Comprehensive Cancer Network guidelines for patients with intermediate- or poor-risk disease: cabozantinib (Cabometyx) plus nivolumab (Opdivo), lenvatinib (Lenvima) plus pembrolizumab (Keytruda), axitinib (Inlyta) plus pembrolizumab, and ipilimumab (Yervoy) plus nivolumab. The first 3 of these regimens are also preferred for favorable-risk disease.

Haas says that patients with a high tumor burden could benefit from cabozantinib/nivolumab or lenvatinib/pembrolizumab since these regimens have a short time to response and can induce a deep response. However, physicians should consider whether patients have autoimmune disease for all regimens with immune checkpoint inhibitors since these patients were excluded from clinical trials of these regimens and they could cause severe adverse events (AEs).

For younger patients, she suggests that ipilimumab/nivolumab could be beneficial due to having the longest durability of response and offering the potential to end treatment. Axitinib/pembrolizumab could be considered for older patients whose priority is avoiding AEs, provided their disease is not rapidly progressing.

 If we focus on just the patients with intermediate- or poor-risk features, because there you have 4 different combinations to consider, I look at their tumor burden. I also look at their underlying health conditions. So if they have a very high tumor burden, and they don't have any serious autoimmune considerations—for example, they don't have lupus or they don't have severe rheumatoid arthritis or Crohn disease, things like that—and they have a high tumor burden, then, generally, I want something that's going to work very quickly. And both cabozantinib/nivolumab and lenvatinib/pembrolizumab have the deepest, quickest responses in those patients. And so those are the kind of the go-to that I use in that setting.

 However, if they were a younger patient, and they have advanced disease, and they meet either intermediate- or poor-risk criteria, I'm also a big fan of ipilimumab/nivolumab because that has the longest durability of response and there are patients that are younger that would like to consider that approach because they have the hope of sustaining a very durable response, and they might eventually be able to come off of therapy. That's always a very attractive option for patients. If they're older, and/or they're [averse to treatment], I think axitinib/pembrolizumab is also a nice option. And if I think their disease isn't kind of rocketing or exploding, I would also offer axitinib and pembrolizumab in that setting.

Naomi B. Haas, MD, discusses how patient characteristics and preference influence the choice of frontline treatment for advanced clear cell renal cell carcinoma. 

Key Considerations for Selecting Frontline Therapy in Advanced RCC

Naomi B. Haas, MD, medical oncologist, director of the prostate and kidney cancer program, and professor of medicine at the Hospital of the University of Pennsylvania, discusses the use of VEGF tyrosine kinase inhibitors (TKIs) as neoadjuvant therapy for renal cell carcinoma (RCC).

TKIs that target VEGF, including cabozantinib (Cabometyx), are currently being explored in the adjuvant and neoadjuvant setting in RCC. A phase 2 study (NCT04022343) of neoadjuvant cabozantinib from Emory University showed its capability to shrink renal cell tumors to enable surgical resection.

According to Haas, a challenge for this approach is that VEGF TKIs can interfere with wound healing, potentially complicating surgical resection and recovery. However, she suggests that this effect can be managed by ending administration of cabozantinib before surgery based on the drug’s 5-day half-life, but not early enough to allow tumor regrowth.

Other studies have shown that this procedure is possible, Haas says. The phase 2 study reported that no surgical complications related to cabozantinib occurred in 15 patients who received surgery.

 A number of VEGF TKI approaches have been taken in the neoadjuvant setting. The general approach has been…given that cabozantinib is 1 of the VEGF TKIs that is thought to be 1 of the most active in RCC—the idea has been with this kind of approach, if it can be administered in a safe way and achieve as much tumor shrinkage as possible.

And one of the challenges with VEGF receptor TKIs in the neoadjuvant setting has been that they interfere with wound healing to some extent. Cabozantinib has a half-life of about 5 days. So, the timing of it has to be such that it can be administered and then allow enough time to stop where the patient can safely proceed with surgery, but also not be off the drugs so much that you get a rebound effect. And I think we've seen with other trials, that is indeed possible.

Naomi B. Haas, MD, discusses the use of VEGF tyrosine kinase inhibitors as neoadjuvant therapy for renal cell carcinoma.

Neoadjuvant Cabozantinib Enables Resection of Advanced RCC If Timed Properly

Naomi Haas, MD, director, Prostate and Kidney Cancer Program, associate professor, Medicine, Hospital of the University of Pennsylvania, discusses the current areas of ongoing research in the treatment landscape for patients with prostate cancer, specifically metastatic castration-resistant disease.

There are several studies exploring bispecific T-cell engager (BiTE) therapies, which is different from other approaches as it allows for repeat dosing that could be an advantage or disadvantage to the patient. Haas says the advantage to BiTE therapy is that the therapy can be generated and don’t need to be made specific.

The CART trials, exploring adoptive chimeric antigen receptor (CAR) T-cell therapies, are patient-specific, so to make a CART, patients must undergo apheresis to remove the T cells, then the T cells are infected with the lentivirus, Haas says. The BiTE therapies are generated more synthetically.

Lutetium is in between in terms of research as there are little data on a second set of repeat dosing. At this time, Haas says CART is where physicians think of 1 dose or maybe a second retreatment dose, lutetium is between 2 and 4 doses, and BiTE therapy is given more chronically to patients.

Naomi Haas, MD, discusses the current areas of ongoing research in the treatment landscape for patients with prostate cancer.

Exploring New Treatment Options in Prostate Cancer Landscape

Naomi Haas, MD, director, Prostate and Kidney Cancer Program, associate professor, Medicine, Hospital of the University of Pennsylvania, discusses the importance of using PSMA, an antigen that is expressed on the cell surface, for the detection of prostate cancer.

PSMA is widely expressed in prostate tissue in cancer, and it isn’t well expressed in normal tissue, Haas says. For that reason, PSMA is a good target because there aren’t as many toxicity concerns with it.

In normal tissue, PSMA is part of the neurotransmission of things, and in intestinal tissue, it helps with folate transfer. People aren’t sure what its function is in prostate tissue, says Haas. However, it an area of important interest at this time based on its high level of expression in prostate cancer.

Naomi Haas, MD, discusses the importance of using PSMA, an antigen that is expressed on the cell surface, for the detection of prostate cancer.

Naomi Haas, MD | Authors

Articles

Factors Influencing Frontline Therapy Options for Favorable-Risk RCC

Key Considerations for Selecting Frontline Therapy in Advanced RCC

Neoadjuvant Cabozantinib Enables Resection of Advanced RCC If Timed Properly

Exploring New Treatment Options in Prostate Cancer Landscape

PSMA Plays Important Role in the Detection of Prostate Cancer