Oncology Decoded

In the newest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, provided a recap of the most critical presentations and data to emerge from the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Specifically, they highlighted the late-breaking abstracts that may transform the standard of care for different prostate cancer populations.
Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Bupathi is president and medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.
Together, they dissected updated results from the following trials:
TALAPRO-3

In the phase 3 TALAPRO-3 trial (NCT04821622), combining talazoparib (Talzenna) with enzalutamide (Xtandi) significantly improved radiographic progression-free survival (rPFS) vs standard enzalutamide monotherapy among patients with metastatic castration-sensitive prostate cancer (CSPC) harboring homologous recombination repair (HRR) alterations. Based on investigator assessment, the median rPFS was not reached (NR; 95% CI, NR-NR) with the talazoparib combination vs 45.8 months (95% CI, 37.7-NR) with enzalutamide plus placebo (HR, 0.481; 95% CI, 0.357-0.647; P <.0001).
Overall, the data supported talazoparib plus enzalutamide as a potential treatment option for patients with HRR-altered metastatic CSPC and highlighted the importance of early molecular testing in prostate cancer.
PROTEUS

Findings from the phase 3 PROTEUS trial (NCT03767244) demonstrated a reduced risk of death or metastasis with apalutamide (Erleada) plus androgen deprivation therapy (ADT) vs placebo plus ADT among patients with high-risk localized or locally advanced prostate cancer. With a median follow-up of 61.7 months, 8.9% of patients in the apalutamide group experienced a pathological complete response (pCR) vs 1% of those who received placebo (OR, 10.17; 95% CI, 5.27-19.64; P <.001). The likelihood of metastasis-free survival at 5 years was 78.2% vs 73.5% in each respective arm (HR, 0.80; 95% CI, 0.67-0.96; P = .02).
According to the study investigators, results from PROTEUS may support apalutamide plus ADT and radical prostatectomy as a new standard of care for patient with high-risk localized or locally advanced disease.
References

Agarwal N, Matsubara N, Azad A, et al. TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2026;44(suppl 17):LBA5007. doi:10.1200/JCO.2026.44.17_suppl.LBA5007

Taplin ME, Gleave M, Shore N, et al. Perioperative (neoadjuvant and adjuvant) apalutamide (APA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with radical prostatectomy (RP) in high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): final analysis of the PROTEUS phase 3 study. J Clin Oncol. 2026;44(suppl 17):LBA1. doi:10.1200/JCO.2026.44.17_suppl.LBA1

In the newest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, convened with their colleagues Suzanne B. Merrill, MD, FACS, and Mark D. Tyson, II, MD, MPH. They broke down the current treatment paradigm for those with non–muscle-invasive bladder cancer (NMIBC) by discussing how novel therapeutic modalities, patient selection criteria, and other practical considerations fit into effective clinical strategies. 
The discussion began with an overview of the effectiveness and limitations associated with Bacillus Calmette-Guérin (BCG), and how clinical trials like the phase 3 KEYNOTE-676 (NCT03711032) and phase 3 POTOMAC (NCT03528694) studies may support novel treatment regimens that incorporate checkpoint inhibitors. The group discussed how immunotherapy agents like pembrolizumab (Keytruda) may play important roles in the treatment of patients with NMIBC, especially in the event of BCG-unresponsive disease or BCG shortages. 
Additionally, the experts spoke about forming effective collaborations between urologists and medical oncologists to optimally care for patients. Specifically, Merrill emphasized a dedicated team approach to check symptoms, process referrals, and handle other tasks when treating patients who are receiving immune checkpoint inhibitors for their diseases. The conversation concluded with the group emphasizing the development of novel treatment delivery systems across the NMIBC space, which may improve outcomes and positively impact patients from a quality-of-life perspective.
Drs. Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Dr. Bupathi is president and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Dr. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.
Merill is a board-certified urologic surgeon at Colorado Urology. Tyson is a urologic oncologist with a subspecialty interest in bladder cancer at Mayo Clinic in Arizona.

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, spoke about the clinical utility of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for those with muscle-invasive bladder cancer (MIBC) and similar patient populations. They highlighted the “transformational” potential of this therapeutic regimen in the context of findings from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124) that investigators presented at the 2026 ASCO Genitourinary Cancers Symposium.

Although certain data from the EV-304 trial, including the improvements in pathologic complete responses (pCRs) with the enfortumab vedotin combination over gemcitabine/cisplatin, represent “historical gamechangers”, the hosts pointed towards some uncertainty related to outcomes for those with varying or mixed histologies. According to Bupathi, it may still make sense to administer chemotherapy with immunotherapy in some of these subgroups. 
The hosts also considered how many cycles of enfortumab vedotin plus pembrolizumab should be administered across the neoadjuvant and adjuvant settings, noting how markers like circulating tumor DNA may help inform treatment schedules. Additionally, they highlighted a need for additional research to clarify whether cystectomy could be spared for patients receiving this combination regimen while translating the benefits observed in trials like EV-304 to the real world.
The discussion also touched upon the treatment of those with metastatic disease, as the hosts considered how dosing cycles, consolidated radiotherapy, and cystectomy with nodal dissection fit into the treatment algorithm for these patients. Garmezy and Bupathi also discussed how the efficacy and safety of the enfortumab vedotin combination compared with gemcitabine plus nivolumab (Opdivo), noting how the EV-304 regimen may be simpler to administer and manage.
Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Bupathi is president of and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.
Reference

Galsky MD, Valderrama BP, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study. J Clin Oncol. 2026;44(suppl 7):LBA630. doi: 10.1200/JCO.2026.44.7_suppl.LBA630

Following the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, Oncology Decoded hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, met to break down the key trials and presentations that may help move the needle in genitourinary oncology. Together, they reviewed findings and clinical implications across various bladder cancer, kidney cancer, and prostate cancer populations.
Among several sessions highlighted during their discussion, the experts covered the following presentations:
1.        Phase 3 KEYNOTE-B15 Trial (NCT04700124)
a.        Enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) significantly prolonged event-free survival (EFS) outcomes vs gemcitabine plus cisplatin among patients with muscle-invasive bladder cancer (MIBC; HR, 0.53; 95% CI, 0.41-0.70; P <.001).
b.       The rate of pathological complete response also improved by an estimated difference of 23.4% (95% CI, 16.7%-29.8%; P <.001) with the enfortumab vedotin combination.
c.        Data from this trial point towards the potential removal of chemotherapy in the perioperative therapy landscape.
2.        Phase 3 LITESPARK-011 Trial (NCT04586231)
a.        Belzutifan (Welireg) plus lenvatinib (Lenvima) improved progression-free survival (PFS; HR, 0.70; 95% CI, 0.59-0.84; P = .00007) and responses vs cabozantinib (Cabometyx) monotherapy among those with advanced clear cell renal cell carcinoma.
b.       Data showed a median duration of response (DOR) of 23.0 months with the belzutifan combination vs 12.3 months with cabozantinib.
c.        Findings may support an eventual FDA approval of belzutifan/lenvatinib in this patient population.
3.        Phase 3 PEACE-3 Trial (NCT02194842)
a.        Combining enzalutamide (Xtandi) with radium-223 (Xofigo) boosted overall survival (OS) compared with enzalutamide alone among patients with metastatic castration-resistant prostate cancer (HR, 0.75; 95% CI, 0.60-0.95; P = .0078).
b.       Previously reported rPFS improvements with the combination were sustained with longer follow-up, as data showed a median rPFS of 19.2 months vs 16.4 months in the experimental and comparator arms, respectively.
Drs. Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Dr. Bupathi is president and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Dr. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.
References

Galsky MD, Valderrama BP, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: randomized, open-label, phase 3 KEYNOTE-B15 study. J Clin Oncol. 2026;44(suppl 7):LBA630. doi:10.1200/JCO.2026.44.7_suppl.LBA630

Motzer RJ, Park SH, McDermott RS, et al. Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti-PD-(L)1 therapy: open-label phase 3 LITESPARK-011 study. J Clin Oncol. 2026;44(suppl 7):417. doi:10.1200/JCO.2026.44.7_suppl417

Gallardo E, Tombal BF, Saad F, et al. Final overall survival results from the EORTC 1333/PEACE-3 trial: enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer. J Clin Oncol. 2026;44(suppl 7):15. doi:10.1200/JCO.2026.44.7_suppl.15

As part of honoring National Cancer Prevention Month in February, RadOnc on the Run host Brandon Mancini MD, MBA, spoke with Jenni Beamer about a broad range of topics dedicated to proactively treating patients who are at risk of developing cancer. 
Beamer, senior executive director for the state of Michigan at the American Cancer Society (ACS), emphasized the importance of having a designated month to educate the public regarding lifestyle choices, regular screenings, and other modifiable risk factors that may influence the likelihood of a cancer diagnosis. Regarding specific campaigns focused on cancer prevention, she brought attention to ACS CancerRisk360, a free digital tool that provides a comprehensive cancer risk evaluation based on key areas like genetic risk, family history, screening adherence, and daily life factors. 
Mancini highlighted how the challenges surrounding cancer prevention have evolved as environmental and exposure-related risk factors have transformed over time. For example, while rates of smoking—a common risk factor for lung cancer—have decreased, vaping has appeared to pick up, which may cause long-term complications in terms of cancer risk. Beamer and colleagues stay up to date on strategies for managing these modifiable risk factors via national roundtables, which also cover areas like breast cancer screening and HPV vaccination.
“Just yesterday, we reported out a 27% decline in cervical cancer incidence rates that are directly related to the implementation of the vaccine. That just gives me chills to know,” Beamer stated. “That’s why my 3 kids have that cancer vaccine. Progress is happening, and it’s in the stories of the everyday people that want to make a difference. I’m so motivated and proud of everyone’s collective energy and work around this.”
Mancini is director at Bold Advanced Medical Future (BAMF) Health, clinical associate professor in the Department of Radiology at Michigan State University College of Human Medicine, and editor-at-large for the RadOnc Review, a supplement of the journal ONCOLOGY®.
Reference

Declines in cervical cancer incidence in U.S. varied substantially by state, aligning with HPV vaccination rates, new ACS study finds. News release. American Cancer Society. February 23, 2026. Accessed February 25, 2026. https://tinyurl.com/57rykdvk