Dear readers,

The 2025 ASCO Annual Meeting provided a lot of new insights; we are still trying to digest all of the information. On Oncology Decoded, we recently ranked our top abstracts (check out the episode online, on Spotify, or on Apple streaming platforms).

In our previous collection, we broke down AMPLITUDE and TALAPRO-2, so we will omit them here. They both made our list; tune in to our podcast to see where they landed. Today, we will discuss some of the other key abstracts that made our Oncology Decoded rankings. Again, stream the episode to hear the full list.

Urothelial Cancer

NIAGARA: This was a HUGE study that already seems to be practice-informing. Many of you will remember that NIAGARA is the perioperative study that observed gemcitabine + cisplatin + durvalumab (4 neoadjuvant cycles with continued adjuvant durvalumab to complete one year of immunotherapy) versus neoadjuvant gemcitabine + cisplatin alone (no adjuvant therapy). This was recently FDA-approved and is now a new standard of care for cisplatin-eligible patients with muscle-invasive disease. Reminder, patients were allowed to have split-dose cisplatin, dropping the CrCl threshold to 40 mL/min!

ASCO 2025 presented new ctDNA analysis from this trial showing that ctDNA is an incredibly powerful prognostic indicator, with a hazard ratio (HR) of 0.42 for event-free survival (baseline draw). The addition of durvalumab improved outcomes in both ctDNA- (HR 0.45) and ctDNA+ (HR 0.73) patients. Post-cystectomy ctDNA analysis showed an HR of event free survival of 0.09, again favoring durvalumab in both groups! While we can’t conclude that the adjuvant durvalumab is helping patients with pathologic complete response and negative ctDNA, the neoadjuvant component may be helping. We cannot exclude that the adjuvant durvalumab is necessary. Therefore, for all patients who start the NIAGRA regimen, we recommend that they complete it. A new standard in perioperative urothelial cancer!

Prostate Cancer

CAN-2409: This randomized phase III study evaluated the injection of CAN-2409 (an oncolytic viral gene therapy) + valacyclovir (prodrug) in patients with localized definitive therapy for intermediate- to high-risk prostate cancer. The therapy led to a 30% relative improvement in disease-free survival, though many of the recurrences were in the prostate gland itself, which is less correlative to overall survival compared to the development of metastasis. Of note, the effect seemed greatest in patients who did not receive androgen deprivation therapy (HR, 0.56) compared to those that did receive ADT (HR, 0.92; CI, 0.5–1.67). Perhaps three injections of CAN-2409 could become an androgen-sparing regimen in the future for a select group of patients.

TheraP: In this phase II study of Lu-PSMA-617 versus cabazitaxel in patients with mCRPC, data were already presented suggesting that PSA50 responses were more frequent with Lu-PSMA-617 (66% vs 37%). They also showed that relative response rates increased with higher median SUV values on PET scan, though Lu-PSMA-617 performed in all patients with PSMA avidity. This abstract showed an increase in clonal hematopoiesis in patients exposed to Lu-PSMA-617 compared to cabazitaxel. Odds of treatment-emergent CH were 3.2x higher for Lutetium, and VAF expansions in DNA damage response genes increased in 87% vs 33%. Clonal hematopoiesis has been linked to the development of hematologic disorders, bone marrow failure, and cardiovascular events. This is an interesting reminder that we need to continue to collect safety data on all patients after a new therapeutic modality is approved. That said, Lu-PSMA-617 is still a strong option for patients with metastatic hormone-resistant prostate cancer.

Renal Cell Carcinoma

ARC-20: This expansion cohort of a phase I trial evaluated the novel HIF2α inhibitor casdatifan + cabozantinib in patients with ccRCC who had progressed on prior therapy. Overall response rate was 60% in patients with prior immunotherapy but no prior VEGF TKI, and 40% in patients with prior immunotherapy and TKI. This was a very interesting signal worthy of further exploration. A second HIF inhibitor would expand treatment options. PEAK-1, a phase III study, is now underway to observe this combination in patients with prior immunotherapy but no prior VEGF TKI (randomized vs cabozantinib monotherapy).

STELLAR-002: Two abstracts were presented: (1) the expansion cohort in front-line ccRCC and (2) the phase I dose escalation experience (Garmezy et al., Abstract 3101 – maybe we are biased). The expansion cohort found that zanzalitinib (new VEGF multi-kinase TKI) and nivolumab had a solid response rate of 63% and a very low primary progressive disease rate of 5%. The addition of relatlimab in a triplet did not seem to improve efficacy. The combination of zanzalitinib and nivolumab is exciting, and phase III testing in non-clear cell RCC is underway (and we expect it will become a new standard of care in papillary RCC and perhaps a few other subtypes). In addition, we have seen a press release that zanzalitinib improved overall survival in colorectal cancer. So much more to come!

Sincerely,
Benjamin Garmezy and Manojkumar Bupathi