Benjamin P. Saylor

Keytruda (pembrolizumab) plus platinum-based chemotherapy was both safe and efficacious in treating penile squamous cell carcinoma (PSCC), according to findings from the phase 2 HERCULES trial presented at the 2024 

American Society of Clinical Oncology Annual Meeting

A phase 2 trial called HERCULES investigated the use of Keytruda (pembrolizumab) combined with platinum-based chemotherapy as a first-line treatment for advanced penile squamous cell carcinoma (PSCC).

The study found that the treatment was safe and efficacious.

A total of 39.4% patients responded to the treatment, with one complete response (disappearance of cancer) and 12 partial responses.

Penile squamous cell carcinoma is a rare disease with a poor prognosis, and platinum-based chemotherapy has been the standard treatment.

Dr. Fernando Cotait Maluf, of Hospital Beneficência Portuguesa de São Paulo and Hospital Israelita Albert Einstein, São Paulo, Brazil, presented the data at the conference. In the presentation, Maluf noted that PSCC has up to a 10 times higher incidence in low-income countries in Africa, Asia and Latin America.He added that advanced PSCC is a disease for which no improvements have been made of late, and prognosis is poor, with an overall survival (OS; time patients live before death of any cause) of approximately six to seven months.

“Platinum-based chemotherapy has been considered the standard of care. … Immune checkpoint inhibitors have been associated with efficacy in different tumor types, including HPV16-positive tumors, such as cervical and head and neck squamous cell carcinoma,”Maluf explained.

Maluf and his coauthors hypothesized that the addition of Keytruda to platinum-based chemotherapy for first-line treatment of advanced penile cancer would be safe and associated with improved outcomes for patients.

Eligible patients were required to have an ECOG performance status of 0 to 1 (meaning that they were able to perform all their daily tasks independently), have metastatic disease, locally advanced disease that is not eligble to curative-intent therapy, loco-regional recurrence (cancer that returned to or nearby the original site) that is not amenable to curative-intent therapy, and no prior exposure to chemotherapy for advanced disease. However, prior presurgical chemotherapy was allowed if disease progressed after 12 months.

A total of 37 patients were included in the study, of whom five (13.5%) had locally advanced disease and eight (21.6%) had loco-regional recurrence. Thirty-three patients were eligible for an analysis to determine how well the treatment regimen worked.

The main goal of the trial was confirmed overall response rate (ORR; percentage of patients whose disease shrinks or disappears), as determined by the investigators on the study. Secondary goals included confirmed ORR by experts not involved in the trial, progression-free survival (PFS; time patients live without disease worsening), OS, safety and analysis of how this research may be able to influence cancer care for this population.

Confirmed ORR by researchers was 39.4%. Of these, one was a complete response, meaning that all signs of cancer disappeared (3%), and 12 (36.4%) were partial responses, meaning that the cancer shrunk but was still detectable on follow-up tests.

Confirmed ORR by experts unaffiliated with the study was 42.4%. Clinical benefit rate (percentage of patients who experience a complete response, partial response or stable disease) by researchers more than 24 weeks was 45.5%.

Maluf reported that tumor shrinkage of any magnitude was seen in 75.8% of patients. After a median follow-up of 24 months, median duration of response was 5.9 months and median time to response was 1.4 months. Median PFS was 5.4 months, and median OS was 9.6 months.

“Our biomarker exploratory analysis showed a potential correlation between response with [tumor mutational burden] as well as HPV16 status,” Maluf reported.

Regarding treatment-related side effects, Maluf reported 19 side effects (51.4%) of grade 3 (moderate) or higher and noted that only six patients (16.2%) experienced neutropenia (decrease in a type of white blood cells). Two (5.4%) immune-related side effects of grade 3 or higher were observed.

“The HERCULES trial is the first trial to demonstrate the efficacy of immune checkpoint inhibitors in [patients with] advanced penile cancer with [a] manageable safety profile. We are proud to say that [Keytruda] plus platinum-based therapy is a new treatment option for [patients with] advanced penile cancer,” Maluf said in his concluding remarks.

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Keytruda plus platinum-based chemotherapy appeared to be safe and effective in treating penile squamous cell carcinoma. 

Keytruda Plus Chemo May Improve Penile Cancer Outcomes

The treatment combination of Welireg (belzutifan) and Cabometyx (cabozantinib) demonstrated durable anti-tumor activity in patients with clear cell renal cell carcinoma (ccRCC) who were treatment-naïve or had previous treatment with immunotherapy, according to results from a phase 2 trial.

The data from the phase 2 trial, LITESPARK-003, were presented at the 

2023 European Society for Medical Oncology (ESMO) Annual Congress

 in Madrid, Spain by Dr. Toni K. Choueiri, professor of medicine at Harvard Medical School and an attending physician, director of the Genitourinary Oncology Disease Center, and director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts.

In his presentation, Choueiri explained that the inactivation of the von Hippel-Lindau gene (VHL; a mutated gene that increases the growth of abnormal cells) results in the overexpression of hypoxia-inducible factors (HIFs; proteins responsible for cell responses to changes in oxygen levels and activate specific genes for cell growth and survival).

Choueiri added that initial results from LITESPARK-003 showed promising anti-tumor activity in patients who were either treatment naïve (cohort 1) or previously treated with immunotherapy (cohort 2).

Cohort 1 had 50 patients enrolled and treated, with a median follow-up of 24.3 months; however, 24 patients discontinued treatment. Cohort 2 had 52 patients enrolled and treated, with a median follow-up of 39.8 months. Forty-six patients discontinued treatment.

At a median follow-up of 14 months, there was a 57% overall response rate (ORR; percentage of patients who had a partial or complete response to treatment) in cohort 1. At a median follow-up of 24.6 months, there was a 31% ORR in cohort 2. At the 2023 ESMO Congress, Choueiri presented updated findings from both cohorts.

In cohort 1, 28 patients (56%) were International Metastatic RCC Database Consortium (IMDC) favorable risk, and 22 patients (44%) were IMDC intermediate/poor risk. In cohort 2, 11 patients (21%) were IMDC favorable risk and 41 patients (79%) were IMDC intermediate/poor risk.

Choueiri reported that ORR in cohort 1 was 70% in the entire cohort, 79% in patients who were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable risk and 59% in patients who were IMDC intermediate/poor risk.

In cohort 2, ORR was 31% in the entire cohort, and 27% in patients who were IMDC favorable risk and 32% in patients who were IMDC intermediate/poor risk.

Choueiri reported that all patients in cohort 1 had a reduction in target lesion size and that in cohort 2, 45 of 51 patients (88%) with available post-baseline imaging saw a reduction in target lesion size.

In cohort 1, the median progression-free survival (PFS; time during and after treatment when the patient lives and the cancer does not worsen) was 30.3 months, and in cohort 2, the median PFS was 13.8 months. In cohort 1, the median overall survival (OS; length of time from diagnosis or start of treatment when a patient still lives) was not reached (meaning more than half of the patients in that cohort had not died) and in cohort 2, the median PFS was 26.7 months.

Any-grade treatment-related side effects were reported in 100% of cohort 1 and 98% of cohort 2. Treatment-related side effects of grade 3 or higher (mild to severe) occurred in 23 patients (46%) in cohort 1 and 33 patients (64%) in cohort 2.

There were no treatment-related deaths in cohort 1, but one patient experienced treatment-related death in cohort 2. Seven patients (14%) in cohort 1 discontinued any drug because of treatment-related side effects, and 11 patients (21%) in cohort 2 discontinued any drug because of treatment-related side effects.

Serious treatment-related side effects were observed in seven patients (14%) in cohort 1 and 16 patients (31%) in cohort 2, with dose reduction because a treatment-related side effect occurred in 38 patients (76%) and 37 patients (71%) in cohorts 1 and 2, respectively.

“(Welireg) plus (Cabometyx) continue to show durable anti-tumor activity in patients with clear cell RCC who are treatment-naïve or previously treated,” Choueiri concluded.

The Welireg-Cabometyx treatment combination demonstrated anti-tumor activity for some patients with clear cell renal carcinoma, according to a phase 2 trial.


Welireg Plus Cabometyx Shows Anti-Tumor Activity in Kidney Cancer Type

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

Treatment with Pluvicto (177-Lu-PSMA-617) improved the duration of time when a patient’s disease did not progress with a favorable safety profile in patients with metastatic castration-resistant prostate cancer (mCRPC) who were taxane-naïve, according to recent results from a phase 3 trial.

Findings from the PSMAfore trial were presented at the 2023 

European Society for Medical Oncology Annual Congress

 in Madrid, Spain, by Dr. A. Oliver Sartor, a professor of medicine, urology and radiology at Mayo Clinic in Rochester, Minnesota.

Eligibility criteria included diagnosis of mCRPC, candidacy for androgen receptor pathway inhibitor (ARPI) change following one progression on prior ARPI treatment and having at least one PSMA-positive and no exclusionary PSMA-negative lesions. Of note, ARPIs are substances that keep prostate cancer cells from growing.

Patients were randomly assigned to Pluvicto or ARPI change (Zytiga [abiraterone]/Xtandi [enzalutamide]).

“Very, very importantly, those people on the hormonal therapies were able to crossover and to receive the lutetium if they in fact had met the (radiographic progression-free survival) end point,” Sartor said.

The study’s primary endpoint was progression-free survival (the length of time when a patient with cancer is alive without disease worsening), and the key secondary endpoint was overall survival (the time from the start of treatment when a patient with cancer is still alive).

A total of 234 patients each received either Pluvicto or ARPI change. Fifty-one patients (21.8%) in the Pluvicto arm discontinued treatment due to radiographic progression versus 146 patients (62.4%) in the ARPI change arm. Of the latter group, 123 patients (84.2%) crossed over to receive treatment with Pluvicto.

Baseline characteristics were similar between the Pluvicto and ARPI change groups. In the Pluvicto group, 119 patients (50.9%) had previously received Zytiga, and 94 patients (40.2%) had previously received Xtandi, whereas in the ARPI change group, 130 patients had previously received Zytiga (55.6%) and 84 patients (35.9%) had previously received Xtandi.

Sartor reported that the primary endpoint of progression-free survival was met, meaning that the results of the trial were similar of the expectations of the researchers before work started on the trial.

“No doubt about it, this is unequivocally a positive trial by the (radiographic progression-free survival) criteria. Quite positive,” Sartor commented.

Median progression-free survival was 12.02 months in the Pluvicto group versus 5.59 months in the ARPI change group.

Looking at radiographic response rates in measurable disease, objective response rate (the percentage of patients with a partial or complete response to treatment) was 50.7% in the Pluvicto group and 14.9% in the ARPI change group. Specifically, there was a 21.1% complete response rate (the disappearance of all signs of cancer from treatment) in the Pluvicto group versus 2.7% in the ARPI change group. Median duration of response (the time from when a patient first responded to treatment until progression or death) was 13.63 months in the Pluvicto group versus 10.05 months in the ARPI change group.

Confirmed PSA decrease of at least 50% was seen in 57.6% of patients in the Pluvicto group compared with 20.4% of patients in the ARPI change arm.

At a median follow-up of 12.72 months, median overall survival was 19.25 months in the Pluvicto group and at a median follow-up of 13.08 months, median overall survival was 19.55 months in the ARPI change group.

Regarding side effects, 77 severe or life-threatening side effects were observed (33.9%) in the Pluvicto group versus 100 (43.1%) in the ARPI change group. Forty-six serious side effects (20.3%) occurred in the Pluvicto group versus 65 (28.0%) in the ARPI change group. There were eight side effects leading to dose adjustment (3.5%) in the Pluvicto group versus 35 in the ARPI change group. Side effects occurring in at least 10% of patients in either arm included dry mouth, weakness, nausea, anemia, fatigue, constipation, decreased appetite, joint pain, COVID-19, diarrhea, back pain, vomiting, leg swelling and weight loss.

“In summary, PSMAfore met the primary (radiographic progression-free survival) end point with a very favorable adverse event profile, in taxane-naive patients with metastatic CRPC,” Sartor said.

Patients with metastatic castration-resistant prostate cancer who were never treated with a taxane derived a progression-free survival benefit from treatment with Pluvicto.

Pluvicto Improves Survival Without Progression in Certain Patients With Prostate Cancer

More than half of patients with metastatic castration-resistant prostate cancer treated with the radioligand therapy 177Lu-PSMA-I&T experienced decreases in prostate-specific antigen (PSA) levels of at least 30%, according to recent study findings.

Findings from this study were presented at the 2023 American Urological Association Annual Meeting in Chicago.

“PSMA-targeted radioligand therapy with lutetium PSMA-617 Is associated with prolonged overall survival in patients with metastatic castration-resistant prostate cancer, but data regarding the oncological efficacy and toxicity of lutetium PSMA-I&T are limited,” explained study author Dr. Derya Tilki, visiting faculty at Koç University in Istanbul, Turkey, and urologist at Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Germany.

For the study, a total of 33 patients with metastatic castration-resistant prostate cancer received a total of 88 cycles of 177Lu-PSMA-I&T.

Oncological outcomes measured included clinical progression-free survival, defined as the time from the first radioligand therapy cycle to any radiological or biological progression of the disease.

“We assessed response according to PSA changes and imaging response,” Tilki said.

The investigators also assessed side effects related to the treatment.

Median patient age at the time of first radioligand therapy cycle was 71.6 years. PSA response of any amount was seen in 22 patients (69%), at least 30% in 18 patients (56%), at least 50% in 11 patients (33%) and at least 90% in six patients (33%).

Clinical progression-free survival following the first cycle of radioligand therapy was 6.3 months, and overall survival following the first cycle was 21.4 months.

Regarding side effects, nephrotoxicity (what occurs when kidneys are damaged by a drug) was observed in four patients; this side effect was considered mild to moderate in two patients, moderate to severe in one patient and severe to life-threatening in one patient. Hematotoxicity (which can lead to bleeding, infection or anemia) was experienced by six patients (18.2%). The investigators also reported six patients with some degree of myelotoxicity (affecting the bone marrow).

Limitations of the study included its retrospective nature as well as the varying histories of the patients included in the study, according to Tilki.

“These are one of the few data for PSMA radioligand therapy with PSMA-I&T in contrast with PSMA-617, and the toxicity profile is very similar (to that of) PSMA-617,” Tilki said in her presentation of the data.

Patients with metastatic castration-resistant prostate cancer treated with radioligand therapy, a form of targeted therapy, had improvements in PSA levels and survival with favorable side effect profiles. 

Benjamin P. Saylor

Keytruda Plus Chemo May Improve Penile Cancer Outcomes

Welireg Plus Cabometyx Shows Anti-Tumor Activity in Kidney Cancer Type

Pluvicto Improves Survival Without Progression in Certain Patients With Prostate Cancer

PSMA-Targeted Therapy May Decrease PSA Levels in Metastatic Prostate Cancer Subset

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