Jennifer Gershman, PharmD, CPh

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 (UTUC) occurs in the lining of the kidney known as the renal pelvis or the ureter, which can develop as low- or high-grade tumors.Low-grade tumors are not invasive, but they frequently recur and can spread.However, high-grade tumors can spread and are usually treated with nephroureterectomy (surgical removal of the kidney and ureter).Steba Biotech’s novel investigational therapy 

 (Immune Photo Active Cancer Treatment) was recently granted Orphan Drug Designation by the FDA for the treatment of adult patients with UTUC, which provides a variety of incentives — research grants, tax credits, protocol assistance — for the development of drugs for rare diseases.Previously, Padeliporfin ImPACT also received Fast Track designation for the treatment of low-grade and unifocal high-grade UTUC.

 became the first FDA approved therapy to treat low-grade UTUC.With limited treatment options available for low-grade UTUC, which is rare but still affects 

 new patients in the U.S. annually, oncologists see an unmet need for nonsurgical therapies for the condition.

ImPACT works by providing intravenous (IV) delivery of the photosensitive drug padeliporfin, which becomes activated as a targeted nonsurgical treatment option.

In a press release, Barak Palatchi, CEO of Steba Biotech said “Our hope is that Padeliporfin ImPACT offers these patients an effective treatment option that preserves their kidney.”This innovative treatment option could help to preserve the kidneys in patients with UTUC where surgery is not the desired course.The FDA has given the go ahead for the 

 phase 3 open-label multicenter trial in adult patients with UTUC.

Patients will be treated with padeliporfin in induction and maintenance treatment phases, with an expected enrollment of 100 study participants.Patients will receive IV administration of padeliporfin 3.66 mg/kg infused over 10 minutes, and each target area will be illuminated for 10 minutes.The induction phase involves 1-3 treatments given 4 weeks apart.Patients who achieve a complete response in the induction phase will move onto the maintenance treatment phase and be followed for 12 months.The primary outcome is the number of patients without UTUC tumors approximately 28 days after the last treatment.

Articles

Drug would mean a nonsurgical treatment option for people with upper tract urothelial cancer.

Padeliporfin ImPACT Receives Orphan Drug Designation for Upper Tract Urothelial Cancer

Adults of any age with cancer are at an increased risk of suffering a 

, so vaccination is especially important in this population. In an interview,

, Pharm.D., BCOP, Clinical Pharmacy Specialist, Hematology/Oncology, Veterans Affairs Pittsburgh Healthcare System (VAPHS), discusses COVID-19 vaccines in urothelial carcinoma patients and what to anticipate for the rest of this year for oncology services.

Have patients with urothelial carcinoma had the opportunity to receive COVID-19 vaccines?

There have been no restrictions for bladder cancer patients receiving COVID-19 vaccinations at VAPHS. The healthcare system was very fortunate to have ample supply of COVID-19 vaccines early on, and mass vaccination began mid-January. I encouraged all of our patients on chemotherapy and immunotherapy to get vaccinated as soon as possible. Patients on active chemotherapy were told not to delay vaccination despite some chemotherapy regimens for bladder cancer resulting in neutropenia.

What are your top counseling points to encourage COVID-19 vaccination?

I specifically stress that they cannot get COVID-19 from the vaccine and make sure to review what the expected side effects are and that it is safe if you have cancer and are receiving treatment. Additionally, I talk to patients about the benefits of vaccination for their family, community and even for us as healthcare providers.

What are examples of your clinical interventions during the pandemic?

Throughout the pandemic we were challenged to find new ways to manage and treat cancer patients while decreasing their contact with the healthcare system. Early in the pandemic, we looked for ways to extend dosing intervals, convert treatments to oral agents, and considered delaying nonessential treatments. Most of our intravenous treatments continued without interruption. We now conduct our oral anticancer therapy clinic as a hybrid between telehealth and face-to-face visits.

What do you changes do you anticipate happening this year at your clinical practice site?

As we move into 2021, we continue to expand our services through telemedicine.During the pandemic, we expanded to a second remote infusion site and are in early talks of expansion to a third site. By opening these remote infusion centers, we can save hours of travel time for our patients and still provide the same level of care.

COVID-19 vaccine is safe — and more than a little advisable — for people with urothelial cancer, says a clinical pharmacist at the VA Pittsburgh Healthcare System.

COVID-19 Vaccines and Innovative Oncology Services for Patients with Urothelial Carcinoma Have Expanded During the Pandemic

Drugmarkers have recently withdraw urothelial cancer indications from two important cancer medications.

Roche announced in early March that it had voluntarily withdrawn the Tecentriq’s (atezolizumab) indication as a treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy.

Two weeks earlier, AstraZeneca announced that it was withdrawing the use of its checkpoint inhibitor Imfinzi (durvalumab) as a treatment for bladder cancer in the United States following a failure to meet endpoints in a post-approval clinical study.

“The Accelerated Approval Program allows people with difficult-to-treat cancers to receive certain new therapies earlier,” Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development, said in a press release. “While the withdrawal of Tecentriq for prior-platinum treated bladder cancer is disappointing, Tecentriq continues to demonstrate benefits across multiple cancer types and therefore remains a meaningful treatment option for many patients.”

The FDA initially granted accelerated approval for the indication for Tecentriq in 2016 for patients who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based neoadjuvant or adjuvant chemotherapy.2

Accelerated approval was based on results of the phase 2 IMvigor210 trial, which showed promising responses in patients receiving second-line Tecentriq versus historical controls.

But continued approval of the indication was contingent upon the results of the phase 3 IMvigor211 trial, which failed to meet its primary end point of overall survival improvement in patients with tumors that express PD-L.

 of Imfinzi indication in the U.S. for previously treated adult patients with locally advanced or metastatic bladder cancer. The withdrawal does not affect the indication for non-small cell lung cancer.

The statement from Dave Fredrickson, executive vice president, oncology business unit of AstraZeneca, in a 

 was not dissimilar from what Roche’s Garrraway had said. “While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded and remain committed to bringing new and innovative options to patients,” said Fredrickson via a press release. 

Imfinzi, an immunotherapy, was granted accelerated approval in May 2017 based on positive results from Study 1108, a phase I/II trial.However, continued approval was dependent on results from the 

 which did not meet its primary endpoints as seen in 

 enables earlier approval for medications treating serious conditions that fill an unmet medical need, and companies are required to continue studying whether the treatment offers clinical benefit in phase 4 confirmatory trials.

Imfinzi as monotherapy or in combination with tremelimumab was evaluated for survival outcomes in the DANUBE phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma across 23 countries.

Patients were randomized to receive Imfinzi monotherapy (1500 mg) administered intravenously (IV) every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered by IV every 4 weeks for up to 4 doses, followed by Imfinzi maintenance (1500 mg) every 4 weeks; or standard of care chemotherapy. Just over a thousand patients were randomly assigned to receive Imfinzi (346), Imfinzi plus tremelimumab (342), or chemotherapy (344). The median overall survival was 14.4 months in the Imfinzi monotherapy group versus 12.1 months in the chemotherapy group. 

In the intention-to-treat population, which reflects the most generalizable results, the median overall survival was 15.1 months in the Imfinzi plus tremelimumab group versus 12.1 months in the chemotherapy group.The results were not statistically significant and so show that Imfinzi did not improve survival outcomes.

After accelerated approval, both drugs fall short of overall survival endpoint. They will stay on the market for other indications.

Urothelial Cancer Indications Withdrawn From Two Important Cancer Meds, Tecentriq and Imfinzi

 type of cancer and it accounts for about 90% of the cases of bladder cancer.(Urothelial cancers arise out of the urothelium that lines the structures of the urinary tract, so they can also occur in the ureters and the kidneys although most occur in the bladder.) Unfortunately, many patients develop advanced muscle-invasive or metastatic disease resulting in poor clinical outcomes with 5%-15% survival rates.Platinum-based chemotherapy is considered the first-line treatment for advanced urothelial carcinoma, but resistance to these therapies is a problem.

 (enfortumab vedotin), a novel drug that specifically targets cancer cells, was evaluated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who previously received platinum-containing chemotherapy and had disease progression during or after treatment with a programmed death receptor-1or programmed death-ligand 1 inhibitor.

 December 18, 2019 for patients with advanced urothelial cancer whose disease has progressed on chemotherapy and immunotherapy. The drug is marketed and distributed by Seagen, which was previously known as Seattle Genetics.

 that they had submitted two supplemental Biologics License Applications for Padcev that were based on the results reported in the 

The trial, dubbed EV-301, was a global, open-label, phase 3 trial that set out to measure the clinical benefit of Padcev compared with standard chemotherapy to assess the primary endpoint of survival in patients with urothelial carcinoma with disease progression despite treatment with other therapies. Padvec was administered at a dose of 1.25 mg/kg of body weight by intravenous infusion over 30 minutes on days 1, 8, and 15 of a 28-day cycle.There were 608 patients randomized across 19 countries to receive Padcev (301 patients) or chemotherapy (307 patients).The median age of study participants was 68 years (range 30-88), and 77.3% of the patients were men. 

A total of 301 deaths that occurred at the time of the interim analysis (134 in the Padvec group and 167 in the chemotherapy group). The risk of death was 30% lower with Padvec than with chemotherapy after a median follow-up of 11.1 months.

One study limitation is that more men than women were included in the study, although that is probably because that men are more at risk of developing urothelial carcinoma. This study demonstrates that there was a significantly longer overall survival with Padcev than with standard chemotherapy and further highlights the important role this novel therapy plays in advanced urothelial cancer.

New drug may be a treatment option for people with the sixth most common type of cancer.

Jennifer Gershman, PharmD, CPh

Articles

Padeliporfin ImPACT Receives Orphan Drug Designation for Upper Tract Urothelial Cancer

COVID-19 Vaccines and Innovative Oncology Services for Patients with Urothelial Carcinoma Have Expanded During the Pandemic

Urothelial Cancer Indications Withdrawn From Two Important Cancer Meds, Tecentriq and Imfinzi

Padvec Prolongs Survival in Locally Advanced or Metastatic Urothelial Carcinoma