Gopa Iyer, MD, section head, Bladder Cancer, Memorial Sloan Kettering Cancer Center, discusses the unmet needs for patients with solid tumors harboring 

Although standard-of-care treatments exist for patients with 

 mutations across different cancer types, these patients may ultimately experience disease progression over time, Iyer explains. Developing a targeted therapy for solid tumors harboring 

 mutations remains an intriguing avenue for research, Iyer adds.

 mutations are relatively rare among individual tumor types; however, the collective population across different solid tumors represents a meaningful number of patients. A tumor-agnostic targeted therapy would stand to benefit these patients, Iyer adds.

The safety and efficacy of nab-sirolimus (ABI-009) monotherapy is under evaluation in the phase 2 PRECISION 1 trial (NCT05103358), a basket study that is currently enrolling patients with malignant solid tumors harboring pathogenic inactivating 

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Gopa Iyer, MD, discusses the unmet needs for patients with solid tumors harboring TSC1/2 mutations.


Dr. Iyer on Unmet Needs for Patients With TSC1/2-mutated Solid Tumors

Gopa Iyer, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses treatment-related adverse events (TRAEs) with erdafitinib (Balversa) in urothelial cancer.

Erdafitinib is approved for patients with locally advanced or metastatic urothelial carcinoma who harbor certain 

 alterations. However, there are several treatment-related adverse events that providers should be aware of. For example, nail changes, such as onycholysis and paronychia, are common. Often, these AEs can be somewhat prevented by using proper hygiene, trimming nails, and using gloves to protect nails. However, if these AEs persist, nail lacquers and protectants can be used. Involving a dermatologist early on can help patients receive counseling on the dry skin and nail changes that occur with erdafitinib, says Iyer.

Ocular toxicities can also occur. About 1 in 5 patients on the BLC2001 trial had central serous retinopathy, which is a class effect of FGFR inhibitors. Before starting erdafitinib, patients should get a baseline eye exam by an ophthalmologist and routine exams by their oncologist, says Iyer. These exams can indicate whether a patient is developing subretinal fluid or central serous retinopathy. In the event that they are, they should stop erdafitinib immediately and see an ophthalmologist.

Lastly, mucositis is a common AE with erdafitinib. Taking prophylactic sodium bicarbonate mouthwashes several times a day can help prevent mucositis from occurring. However, if a patient develops mucositis, dexamethasone mouth rinses can often alleviate those symptoms, concludes Iyer.

Gopa Iyer, MD, discusses treatment-related adverse events (TRAEs) with erdafitinib (Balversa) in urothelial cancer.

Dr. Iyer on TRAEs With Erdafitinib in Urothelial Cancer

Gopa Iyer, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses treatment-related adverse events (TRAEs) with erdafitinib (Balversa) in urothelial cancer.

Erdafitinib is approved for patients with locally advanced or metastatic urothelial carcinoma who harbor certain 

 alterations. However, there are several treatment-related adverse events that providers should be aware of. For example, nail changes, such as onycholysis and paronychia, are common. Often, these AEs can be somewhat prevented by using proper hygiene, trimming nails, and using gloves to protect nails. However, if these AEs persist, nail lacquers and protectants can be used. Involving a dermatologist early on can help patients receive counseling on the dry skin and nail changes that occur with erdafitinib, says Iyer.

Ocular toxicities can also occur. About 1 in 5 patients on the BLC2001 trial had central serous retinopathy, which is a class effect of FGFR inhibitors. Before starting erdafitinib, patients should get a baseline eye exam by an ophthalmologist and routine exams by their oncologist, says Iyer. These exams can indicate whether a patient is developing subretinal fluid or central serous retinopathy. In the event that they are, they should stop erdafitinib immediately and see an ophthalmologist.

Lastly, mucositis is a common AE with erdafitinib. Taking prophylactic sodium bicarbonate mouthwashes several times a day can help prevent mucositis from occurring. However, if a patient develops mucositis, dexamethasone mouth rinses can often alleviate those symptoms, concludes Iyer.

Gopa Iyer, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the challenges faced with identifying an optimal screening methodology to select patients with bladder cancer for FGFR inhibitor therapy.

One of the big issues in bladder cancer has to do with finding the right biomarkers. The question is whether these markers will be a fusion, a mutation, overexpression on an RNA level, or amplification of the gene, says Iyer; the answer remains unknown.

To date, the only FDA approval in this space is for erdafitinib (Balversa), and the use of this agent is based upon screening for 

 fusions, says Iyer. Now that an FDA option is available, conducting testing or sequencing in the metastatic setting is covered by insurance. Many patients with metastatic disease should be tested to see if they meet those criteria of eligibility for erdafitinib therapy, adds Iyer.

In the muscle-invasive setting, it is a bit more challenging, says Iyer. Certainly, sequencing of muscle-invasive specimens can be performed but the main issue will be obtaining insurance coverage because no FDA approval for muscle-invasive 

-mutant bladder cancer exists yet, concludes Iyer.

Gopa Iyer, MD, discusses the challenges faced with identifying an optimal screening methodology to select patients with bladder cancer for FGFR inhibitor therapy.

Dr. Iyer on Challenges With Selecting Patients With Bladder Cancer for FGFR Inhibitors

Gopa Iyer, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses investigational FGFR inhibitors in metastatic urothelial carcinoma.

In a phase I study, the pan-FGFR kinase inhibitor infigratinib demonstrated an overall response rate of 25.4% in patients with advanced or metastatic urothelial carcinoma with 

 activating mutations or fusions and prior platinum-based chemotherapy. Currently, the agent is being tested in the phase III PROOF 302 trial as adjuvant therapy in high-risk patients with invasive urothelial carcinoma and susceptible 

Rogaratinib is another agent under investigation for patients with metastatic disease. However, the agent is being evaluated in patients with 

 overexpression, as detected with an RNA-based assay, rather than 

Currently, rogaratinib is being compared with chemotherapy in the phase II/III FORT-1 study in patients with 

-positive locally advanced or metastatic urothelial carcinoma who have received prior platinum-containing chemotherapy. Additionally, the agent is being studied in combination with atezolizumab (Tecentriq) in the phase Ib/II FORT-2 trial as first-line treatment for cisplatin-ineligible patients with 

-positive locally advanced or metastatic urothelial carcinoma.

Finally, pemigatinib is being evaluated as a single-agent and in combination with pembrolizumab (Keytruda) in the phase II FIGHT-205 study. Patients must have newly diagnosed, metastatic or unresectable urothelial carcinoma and harbor an 

 mutation or rearrangement to be eligible for enrollment. Another FGFR inhibitor from AstraZeneca that will be looked at alone and in combination with durvalumab (Imfinzi) is in development, Iyer concludes.

Gopa Iyer, MD, discusses investigational FGFR inhibitors in metastatic urothelial carcinoma.



Dr. Iyer on Investigational FGFR Inhibitors in Metastatic Urothelial Carcinoma

Gopa Iyer, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses treatment-emergent hyperphosphatemia with erdafitinib (Balversa) in patients with metastatic urothelial cancer.

In April 2019, the FDA granted accelerated approval to erdafitinib for the treatment of patients with locally advanced or metastatic urothelial cancer with an 

 alteration that has progressed on platinum-containing chemotherapy.

FGFR inhibitors like erdafitinib appear to increase phosphorus reabsorption in the body and lead to hyperphosphatemia, explains Iyer.

Generally, hyperphosphatemia can be controlled with dietary changes such as reducing dairy and meat intake and adding oral phosphate binders like sevelamer (Renagel), says Iyer.

Notably, phosphate levels indicate response to erdafitinib, says Iyer. The FDA designation recommends starting patients on erdafitinib at a daily dose of 8 mg. If a patient’s phosphate level is <5.5 mg/dL after 2 to 3 weeks of treatment, the dose should be increased to 9 mg once daily to increase FGFR inhibition.

Gopa Iyer, MD, discusses treatment-emergent hyperphosphatemia with erdafitinib in patients with metastatic urothelial cancer. 


Dr. Iyer on Erdafitinib-Related Hyperphosphatemia in Metastatic Urothelial Cancer

Gopa Iyer, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the standard chemotherapy options for patients with bladder cancer, but mentions how other agents are evolving the landscape. Iyer shared this insight during the 2016 

 State of the Science Summit on Genitourinary Cancers.

For the last 20 years, treatment has been standard chemotherapy with cisplatin in combination with a number of other chemotherapy agents, Iyer explains. While these therapies have resulted in responses in a little over 50% of patients, most of them will relapse. When physicians try to give chemotherapy in the second-line setting, the responses are only about 10% to 15%, Iyer adds.

However, there has been a sea change in the last 6 to 8 months or so with the FDA approval of the immunotherapy agent atezolizumab (Tecentriq) in patients with metastatic bladder cancer whose disease has already progressed on chemotherapy.

There are standard chemotherapy options available for patients. However, it is important for researchers and physicians to determine when to use immunotherapy in these patients and how to manage associated adverse events.

Gopa Iyer, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the standard chemotherapy options for patients with bladder cancer, but mentions how other agents are evolving the landscape. Iyer shared this insight during the 2016 OncLive® State of the Science Summit on Genitourinary Cancers.

Dr. Iyer on Evolving Treatments in Bladder Cancer

Gopa Iyer, MD, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses significant points for community oncologists to be aware of when treating patients with bladder cancer with immunotherapy agents.

One of the main advantages of immunotherapy, Iyer says, is that it is associated with durable responses. Although the overall response rates with these agents have been relatively low, between 15% and 24%, studies are starting to show that 70% to more than 80% of those patients are responding to treatment for up to 1 year out. This speaks to the durability of response and tolerability from immunotherapy, Iyer says.

However, in a small percentage of patients, it can appear as if they are progressing on their disease, Iyer explains.  

For example, after 3 treatments with atezolizumab (Tecentriq), physicians may notice that lesions have increased in size, though patents seem to be clinically benefiting from treatment. This is likely a case of pseudo progression, in which the immune cells are starting to infiltrate and attack the tumor. Many of these patients will continue on treatment despite this, as long as they are gaining clinical benefit.

On a follow-up scan after another 3 months, he explains, it is likely that oncologists will observe tumor shrinkage.  

Gopa Iyer, MD

Articles

Dr. Iyer on Unmet Needs for Patients With TSC1/2-mutated Solid Tumors

Dr. Iyer on TRAEs With Erdafitinib in Urothelial Cancer

Dr. Iyer on TRAEs With Erdafitinib in Urothelial Cancer

Dr. Iyer on Challenges With Selecting Patients With Bladder Cancer for FGFR Inhibitors

Dr. Iyer on Investigational FGFR Inhibitors in Metastatic Urothelial Carcinoma

Dr. Iyer on Erdafitinib-Related Hyperphosphatemia in Metastatic Urothelial Cancer

Dr. Iyer on Evolving Treatments in Bladder Cancer

Dr. Iyer on Advice for Physicians Using Immunotherapy in Bladder Cancer