Hannah Clarke

Patients with locally advanced or metastatic urothelial cancer, a type of bladder cancer, experienced improvements in progression-free survival (PFS) and overall survival (OS) when 

treated with Padcev (enfortumab vedotin-ejfv) plus Keytruda (pembrolizumab)

 versus platinum-based chemotherapy without negative impact to quality of life (QOL), pain or functioning, according to patient-reported outcome (PRO) data from the phase 3 EV-302 trial.

In total, the EV-302 trial enrolled 886 patients with locally advanced or metastatic urothelial cancer who were assigned to receive either Padcev and Keytruda (442 patients) or to receive platinum-based chemotherapy (444 patients). All patients included in the trial were treated until disease progression, unacceptable toxicity or the completion of maximum cycles.

The combination of Padcev (enfortumab vedotin-ejfv) and Keytruda (pembrolizumab) for patients with locally advanced or metastatic urothelial cancer helped patients live longer overall (overall survival) and live longer without their disease worsening (progression-free survival), compared to chemotherapy.

The combination of Padcev and Keytruda did not negatively impact patients’ quality of life, pain levels or functioning.

Patients given Padcev and Keytruda lived for a longer period of time before their pain progressed compared to those given chemotherapy.

Previously reported data from the EV-302 trial

 showed that the combination of Padcev and Keytruda nearly doubled PFS (the time a patient lives without their disease spreading or progressing) and OS (the time a patient lives, regardless of disease status) when compared with chemotherapy in patients with locally advanced or metastatic urothelial cancer.

Specifically, the median PFS was 12.5 months with Padcev and Keytruda, versus 6.3 months in the chemotherapy group. The median OS was 31.5 months in the Padcev and Keytruda group, compared with 16.1 months in the chemotherapy group.

Updated data from the EV-302 trial were presented at 

the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting

 by Dr. Shilpa Gupta, director of Genitourinary Medical Oncology at Taussig Cancer Institute and co-leader of the Genitourinary Oncology Program at Cleveland Clinic.

“We know that patients with locally advanced and metastatic urothelial cancer have a poor prognosis, with an estimated five-year survival of less than 8% globally. And they have a high symptom and pain burden, which impacts their quality of life and functioning,” Gupta noted during the presentation. “Here, we report the PRO data from the EV-302 trial, including impacts on patient's quality of life, functioning and disease symptoms.”

At the start of the trial, QOL and pain scores were similar among patients in the two treatment groups.

Time to pain progression (TTPP) was previously reported, showing a median TTPP of 14.2 months in the Padcev and Keytruda group and 10 months in the chemotherapy group. No statistically significant difference between the two groups was observed, meaning that researchers could not say with certainty that one treatment regimen truly led to a superior outcome.

Further, patients in the Padcev and Keytruda group demonstrated larger improvements in worst pain per the Brief Pain Inventory Short Form (BPI-SF) assessment compared with those in the chemotherapy group. However, neither group reached the pre-defined thresholds for a clinically meaningful improvement.

Among those with moderate/severe pain at baseline (approximately one-third of patients), a clinically meaningful improvement in worst pain per BPI-SF was observed in both treatment groups. The BPI-SF is a questionnaire used to measure how pain affects a patient’s daily functioning in tasks like mood, walking ability, work, relationships, sleep and enjoyment of life. Those in the Padcev and Keytruda group experienced greater improvements in pain compared with those in the chemotherapy group.

The investigators also assessed changes in the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), which measures global health status (GHS; overall patient wellbeing) and QOL.

Patients in the Padcev and Keytruda group demonstrated a worsening in GHS/QOL score at week 3, with a return to baseline at week 4. Patients in the chemotherapy group demonstrated a worsening in GHS/QOL from week 1 through week 17, with a return to baseline from week 20. Overall, the median time to confirmed deterioration was 5.9 months in the Padcev and Keytruda group versus 3.2 months in the chemotherapy group.

Among those with moderate/severe pain at baseline, patients in the Padcev and Keytruda group showed a clinically meaningful improvement in GHS/QOL compared with the chemotherapy group. Both cisplatin-eligible and cisplatin-ineligible patients in the Padcev and Keytruda group showed a transient worsening in GHS/QOL through week 3, with a return to baseline at week 4. Padcev and Keytruda appeared to perform better in cisplatin-eligible patients compared with chemotherapy.

Additionally, patients in the Padcev and Keytruda group demonstrated improved functioning across all functioning domains in the EORTC QLQ-C30 assessment compared with those in the chemotherapy group, assessed by a change from baseline to week 26.

Safety data from the EV-302 study was consistent with previous studies and showed that Padcev and Keytruda was generally manageable.

Gupta concluded in the presentation, “The PRO data presented here complements the published clinical efficacy and safety data, add the patient's voice and support the use of [Padcev and Keytruda] for patients with locally advanced/metastatic urothelial cancer.”

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Padcev and Keytruda improve survival and progression among patients with bladder cancer, but don’t adversely impact pain, functioning or quality of life.

Padcev Plus Keytruda Doesn’t Worsen Quality of Life in Bladder Cancer

Xtandi plus Pluvicto improved PSA progression-free survival in certain patients with prostate cancer, research showed.

Patients with metastatic castration-resistant prostate cancer (mCRPC) experienced improved prostate-specific antigen (PSA) progression-free survival (PSA-PFS) when treated with Pluvicto (Lu-PSMA-617) and Xtandi (enzalutamide) compared with Xtandi alone, according to interim findings from the phase 2 ENZA-p study presented at the 

2023 European Society of Medical Oncology (ESMO) Congress

 as the time to two consecutive increases in PSA (a protein that is associated with the presence of prostate cancer in the body) of 50% and five or more nanograms/milliliter above nadir or death.

“This is the first randomized trial combining an androgen receptor signaling inhibitor, (Xtandi), with (Pluvicto). It provides strong evidence for an enhanced anti-cancer effect with the combination of (Xtandi) and (Pluvicto) based on the primary end point, PSA-PFS,” said Dr. Louise Emmett during an oral presentation of the findings at the ESMO meeting. Emmett is the director of theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney, Australia.

Data from the study showed a median PSA-PFS of 13 months with the combination therapy compared with 7.8 months with Xtandi alone. Median radiographic PFS was 16 months with the combination therapy compared with 12 months for Xtandi alone.

Further, PSA 50% (decrease of at least 50% from baseline) response rates were 93% (77 of 83 patients) in the combination arm, compared with 68% (54 of 79 patients) for Xtandi alone. PSA 90% (decrease of at least 90% from baseline) response rates were 78% (65 of 83 patients) among those in the combination arm compared with 37% (29 of 79 patients) among those who received Xtandi alone.

In total, the ENZA-p study included 162 patients with mCRPC. Patients were randomly assigned 1:1 to two groups: 79 patients were in the Xtandi alone group and 83 patients in the Xtandi plus Pluvicto group.

Those included in the combination therapy arm underwent two doses with Pluvicto with SPECT with two additional doses for those with persistent PSMA-positive disease detected at 92-day follow-up. In total, 81% of patients in the combination arm received four doses of Pluvicto.

Emmett commented in the presentation, “We used two to four doses of (Pluvicto) in the ENZA-p trial, but two to six doses may further improve progression-free survival, particularly in those patients who have a high proportion of androgen persistent clones.”

Serious side effects were reported in 28 of 79 patients (35%) who received Xtandi alone, compared with 27 of 81 patients (33%) who received Xtandi with Pluvicto. Grade 4 or 5 side effects were reported among three of 79 patients (4%) in the Xtandi monotherapy arm, compared with eight of 81 patients (6%) in the combination arm.

In the presentation conclusion, Emmett noted, “I think this is going to become more important as we move this radiation treatment earlier in the disease paradigm to hormone sensitive prostate cancer. It (has) the potential to reduce toxicity by only administering if persistent PSMA-avid disease is present on the PSMA-PET or SPECT images.”

Emmett also added that there is planned follow-up of PFS and overall survival (OS, the time a patient lives following treatment) in the study until July 2024.

Data presented at ESMO “provides strong evidence for an enhanced anti-cancer effect with the combination” of Pluvicto and Xtandi, according to one expert.

Pluvicto Plus Xtandi Enhances Anti-Tumor Activity for Some Patients With Prostate Cancer

Side effects resulting from treatment with Talzenna (talazoparib) plus Xtandi (enzalutamide) in men with metastatic castration-resistant prostate cancer were generally manageable with dosing changes or supportive care, according to safety results from a recent study.

Findings from the phase 3 TALAPRO-2 study were presented during the 2023 

“TALAPRO-2 is the first phase 3 study to evaluate (Talzenna) plus (Xtandi) as a first-line treatment in patients with metastatic castration resistant prostate cancer,” said Dr. Arun Azad, medical oncologist at Peter MacCallum Cancer Centre in Australia, during a presentation of the results. “Here we provide a detailed overview of the safety profile of (Talzenna) plus (Xtandi) in the all-comers population of the TALAPRO-2 trial, with the aim of understanding how (side effects) were managed.”

 were randomly assigned Talzenna or placebo plus Xtandi. A total of 398 patients were included, which included patients with homologous recombination repair gene alterations. According to the National Cancer Institute, changes in the homologous recombination repair pathway can lead to the inability to repair DNA and potentially diseases like cancer.

While most patients experienced side effects on the TALAPRO-2 study, the majority of them were not severe.

Data showed that 98.5% of patients experienced all-cause any-grade treatment-emergent side effects. Serious treatment-emergent side effects were experienced in 19.6% of patients, and 19.1% discontinued treatment with Talzenna due to these side effects. The rate of discontinuation of placebo due to treatment-emergent side effects in the placebo/Xtandi cohort was 12.2%.

The most common severe or life-threatening treatment-emergent side effect in the Talzenna/Xtandi arm was anemia (65.8%), which led to a discontinuation of treatment in 8.3% of patients. The median time to first onset of severe or worse anemia in patients was 3.3 months, and the median duration was 16 days. Anemia was managed in patients using dose modification once anemia was severe or worse, and/or with standard supportive care. Among all patients, 43.2% received dose reduction due to anemia.

“Despite dose reduction, the relative dose intensity of (Talzenna) remained high, above 80%. The incidence of (Talzenna) dose interruptions and reductions was similar during the all-comers and (homologous recombination repair) deficient only populations. However, the rate of (Talzenna) discontinuation due to (side effects) was about half in the (homologous recombination repair) deficient cohort compared to the all-comers cohort,” said Azad.

Other common blood-related treatment-emergent side effects in the all-comers cohort included neutropenia (low number of neutrophils, a type of white blood cell), which was observed in 35.7% of patients, and thrombocytopenia (lower than normal number of platelets in blood that can lead to easy bruising and excessing bleeding), which was observed in 24.6% of patients. Median onset of neutropenia was 2.3 months, and median duration was 12 days. Median onset of thrombocytopenia was 2.3 months, and median duration was 19 days.

The three most common non-hematologic treatment emergent side effects included fatigue (33.7%), back pain (22.1%) and decreased appetite (21.6%).

Overall, the median treatment duration of Talzenna was 19.8 months. Severe or worse treatment-emergent side effects typically occurred early in treatment (within six months of starting treatment) and resolved in less than a month with dose modification and supportive care.

Similar incidence of all-cause treatment-emergent side effects was seen between the all-comers cohort and the homologous recombination repair deficient only cohort.

TALAPRO-2 is an ongoing phase 3 study ofTalzenna plus Xtandi in patients with metastatic castration-resistant prostate cancer. Patients were divided into two groups, made up of those with and without homologous recombination repair gene alterations (all-comers) and a homologous recombination repair -deficient only cohort.

The trial recently reported a clinically meaningful and statistically significant improvement in radiographic progression-free survival (the time during and after treatment when a patient with cancer is alive without disease worsening, as confirmed through radiography) among patients receiving Talzenna plus Xtandi versus placebo plus Xtandi, regardless of homologous recombination repair status.

At the time of data presentation, the median radiographic progression-free survival had not yet been met for patients receiving Talzenna and Xtandi, compared with 21.9 months among those receiving placebo plus Xtandi. Overall, the addition of Talzenna was found to reduce the risk of progression or death by 37%.

Side effects such as anemia and other blood-related events were resolved with dose reductions and/or supportive care in men with metastatic castration-resistant prostate cancer. 

Hannah Clarke

Padcev Plus Keytruda Doesn’t Worsen Quality of Life in Bladder Cancer

Pluvicto Plus Xtandi Enhances Anti-Tumor Activity for Some Patients With Prostate Cancer

Side Effects Manageable From Talzenna/Xtandi Treatment in Prostate Cancer Subset

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