Oncology Decoded

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

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, convened with Meredith Pelster, MD, MSCI; and Jason Henry, MD. Together, they looked back at the presentations and data shared at the 2026 ASCO Gastrointestinal Cancers Symposium that may have long-term impacts on community oncology practice across different gastrointestinal (GI) malignancies, including pancreatic cancer and colorectal cancer (CRC).
Trials and sessions of interest included the following:
Phase 1 Trial (NCT06179160) of INCB161734
o   INCB161734, an investigational KRAS G12D small molecule inhibitor, displayed a manageable safety profile among patients with advanced or metastatic pancreatic ductal adenocarcinoma.
o   The agent produced a disease control rate of 73% (n = 16/22) given at 600 mg once daily and 86% (n = 25/29) when given at 1200 mg once daily.
Phase 3 BREAKWATER Trial (NCT04607421)
o   Among those with BRAF V600E-mutated metastatic CRC, encorafenib (Braftovi) plus cetuximab (Erbitux) and chemotherapy improved the overall response rate (ORR) at 64.4% vs 39.2% with chemotherapy with or without bevacizumab (Avastin) in the control arm (OR, 2.76; 95% CI, 1.42-5.35; P = .001).
o   Overall, the data supported the encorafenib-based combination as a new potential standard of care in BRAF V600E-mutated metastatic CRC.
o   The FDA recently granted traditional approval to the encorafenib regimen based on data from the BREAKWATER trial.
Phase 3 COMMIT Trial (NCT02997228)
o   Chemotherapy in combination with bevacizumab and atezolizumab (Tecentriq) improved outcomes among patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) metastatic CRC vs atezolizumab alone.
o   Data showed a median progression-free survival (PFS) of 30.0 months vs 4.3 months in the combination and monotherapy arms, respectively.
Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.
Pelster is associate director of GI Cancer Research at SCRI Oncology Partners and specializes in treating GI cancers as well as head and neck cancers. Henry is associate director of Drug Development at Sarah Cannon.
References

Wainberg ZA, Henry JT, Park H, et al. Preliminary phase 1 results of INCB161734, a novel oral Kirsten rat sarcoma (KRAS) G12D inhibitor, as monotherapy or in combination with chemotherapy for advanced/metastatic pancreatic duct adenocarcinoma (PDAC). J Clin Oncol. 2026;44(suppl 2):654. doi:10.1200/JCO.2026.44.2_suppl.654

Kopetz S, Wasan HS, Yoshino HS, et al. BREAKWATER: primary analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). J Clin Oncol. 2026;44(suppl 2):13. doi:10.1200/JCO.2026.44.2_suppl.13

FDA grants traditional approval to encorafenib for metastatic colorectal cancer with a BRAF V600E mutation. News release. FDA. February 24, 2026. Accessed February 25, 2026. https://tinyurl.com/4xr84a6y

Rocha Lima CMS, Yothers G, George TJ, et al. Colorectal Cancer Metastatic dMMR Immunotherapy (COMMIT) study: a randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo (FFX/bev) in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC)— NRG-GI004/SWOG-S1610. J Clin Oncol. 2026;44(suppl 2):14. doi:10.1200/JCO.2026.44.2_suppl.14

In a special episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, spoke with their colleague Debapriya Mondal, MBBS, MD, DrNB, who connected to the conversation from India. Collectively, the trio reviewed how clinical practice may differ in US- and India-based institutions, specifically as it relates to the treatment of patients with prostate cancer. 
According to Mondal, while prostate cancer does not represent one of the top 5 most diagnosed cancer types in India overall, patients appear to present with disease more often in cities like New Delhi, Kolkata, and Bangalore. Additionally, many patients in India appear to be diagnosed with more advanced stages of disease compared with reports in the US. 
Regarding medical practices in the US and India, the group discussed potential differences in treatment pathways and specialties that are initially involved in care. Additionally, they highlighted how urologists decide on sequencing androgen deprivation therapy, androgen receptor pathway inhibitors, and other modalities based on region-specific considerations.
The conversation also touched upon the costs of various therapies between regions, as Mondal outlined how patients in India may have access to cheaper generic products for reference drugs like olaparib (Lynparza) and rucaparib (Rubraca). Despite other differences in terms of insurance coverage and barriers to treatment access between regions, the group noted certain international similarities in their respective treatment models, including strategies for the management of advanced or localized disease. 
Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers. Mondal is a consultant medical oncologist from Foris Healthcare in Kolkata, West Bengal, India.

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, wound the clock back to 2025 to discuss the key findings and clinical developments that may propel the genitourinary oncology field forward. Following a breakdown of last year’s breakthroughs in kidney cancer and bladder cancer care, the hosts reviewed the biggest headlines and milestones of 2025 related to prostate cancer management and research. 
Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers. Together, they spoke about several major prostate cancer happenings throughout 2025, including but not limited to:
·      The FDA Approval of the Phase 3 ARANOTE Trial (NCT04736199) Regimen

o   In June 2025, the FDA approved darolutamide (Nubeqa) for patients with metastatic castration-sensitive prostate cancer (CSPC) based on findings from the phase 3 ARANOTE trial.
o   Topline data showed a median radiographic progression-free survival (rPFS) that was not reached (NR) with darolutamide vs 25 months (95% CI, 19-NR) with placebo (HR, 0.54; 95% CI, 0.41-0.71; P <.0001).
o   This approval may grant easier access to darolutamide, especially for the treatment of patients who are older or who present with certain neurocognitive disorders.
·      The FDA Approval of the Phase 3 AMPLITUDE Trial (NCT04497844) Regimen

o   December 2025 saw the FDA approval of niraparib and abiraterone acetate (Akeega) plus prednisone for adults with suspected or deleterious BRCA2-mutated CSPC.
o   Supporting data from the phase 3 AMPLITUDE trial showed a median rPFS that was not estimable (NE; 95% CI, 41 months-NE) in the niraparib arm vs 26 months (95% CI, 18-28) in the placebo arm among 323 patients with BRCA2-mutated disease.
o   This approval for patients with BRCA2-mutations reinforces the importance of conducting upfront genetic testing.
·      Phase 3 PSMAddition Trial (NCT04720157)

o   Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT) significantly prolonged rPFS vs ARPI/ADT treatment alone among patients with prostate specific-membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer (HR, 0.72; 95% CI, 0.58-0.90; P = .002).
o   Other data from ESMO Congress 2025 showed that the lutetium Lu 177 combination numerically improved the overall response rate at 85.3% (95% CI, 79.9%-89.6%) vs 80.8% (95% CI, 74.8%-85.8%) in the control arm.
o   The safety profile observed in the trial may raise questions over whether it is worthwhile to administer all 6 cycles of lutetium Lu 177 to patients.

References

FDA approves darolutamide for metastatic castration-sensitive prostate cancer. News release. FDA. June 3, 2025. Accessed January 20, 2026. https://tinyurl.com/yhde24zj

FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. News release. FDA. December 12, 2025. Accessed January 20, 2026. https://tinyurl.com/rcxaj98

Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Ann Oncol. 2025;36(suppl 2):S1627-S1628. doi:10.1016/j.annonc.2025.09.101