As ASCO 2025 approaches, all eyes are on the pivotal trials that could shift standards, reshape narratives, and spark new questions for oncology strategy. From groundbreaking trials in mBC to paradigm-challenging immunotherapy in colon cancer, this year’s line-up is anything but business as usual.
Here’s a look at four key themes our team is watching and the strategic conversations we expect them to ignite.
DESTINY BREAST-09
Enhertu continues to rewrite the rule book for HER2+ mBC
Enhertu’s standout PFS results in DESTINY-Breast03 have set high expectations for the 1L trial, DESTINY-Breast09. A positive result for Enhertu + pertuzumab (with monotherapy data pending) challenges a decade-old standard and raises the prospect of a new, chemo-free 1L option.
Key discussion points are expected to include:
- Duration of therapy: Use of Enhertu + pertuzumab until progression raises important questions around toxicity, particularly ILD risk, as well as quality of life and economic burden
- Impact of the evolving landscape: While Enhertu is expected to outperform emerging data from HER2CLIMB-05 and PATINA, there is growing interest in integrated approaches, i.e., Enhertu induction with novel maintenance strategies
- Sequencing implications: Caution exists around retreatment with Enhertu in the metastatic setting, and future sequencing decisions will become more complex as Enhertu continues to move earlier in the treatment pathway
SERENA-06
SERD shake-up: A new chapter in endocrine therapy?
The oral SERD story has been anything but straightforward, marked by high-profile setbacks and just one approval to date (elacestrant in 2L+ ER+/HER2– ESR1-mutant disease). ASCO 2025 adds a new chapter, with two key presentations: (1) SERENA-6, moving SERDs to 1L and signalling a shift to pre-emptive treatment adjustment based on molecular relapse, and (2) the first pivotal data for PROTACs as potential rivals to oral SERDs.
Key conversations will center on:
- Readiness to shift in 1L: Will the SERENA-6 data be compelling enough to support routine ESR1 testing during first-line therapy, and how quickly could it be integrated into clinical practice?
- Sequencing and differentiation: If camizestrant moves into 1L, what scope remains for vepdegestrant? Does the mechanistic differentiation support sequential use?
- Competitor SERDs: More 1L trials are expected to read out later this year (e.g. persevERA), but what is the sentiment surrounding giredestrant following 2L failure?
ASCENT-04
Turning the page on chemotherapy in 1L TNBC
A key player in later-line TNBC, Trodelvy now has 1L in its sights. In ASCENT-04, the combination with pembrolizumab met the primary PFS endpoint in the first-line PD-L1+ setting. In a setting where over half of patients may never reach second-line therapy, these data could mark a meaningful step forward both for patients and commercially for Trodelvy. This trial also reinforces a broader trend: ADC + IO combinations pushing into 1L, aiming to reshape standards and reduce dependence on chemotherapy.
The discussions we expect:
- Will PFS be enough for practice change, particularly considering concerns around significant toxicity?
- Future competition with Datroway, and other TROP-2 ADCs, looming, with Tropion-Breast05 readout expected next year
- Scope to shift into PD-L1 negative? For now, the focus is on PD-L1+, but results from ASCENT-03 and Tropion-Breast02, pitting TROP-2 ADCs against chemo in 1L PD-L1-negative metastatic TNBC are expected this year.
ATOMIC
A pivotal shift in dMMR colon cancer – but is it the whole story?
Immune checkpoint inhibitors (ICIs) have transformed the treatment of metastatic dMMR/MSI-H colon cancer, and attention is now shifting to earlier-stage disease. ATOMIC is the first randomized trial to assess ICIs in stage III dMMR/MSI-H colon cancer (investigating use in the adjuvant setting).
How might the discussion unfold?
- Potential to redefine SoC – but for all?
ATOMIC could shift the standard of care in adjuvant stage III dMMR/MSI-H colon cancer. But this subgroup is already risk-stratified, and ongoing ctDNA studies aim to refine adjuvant chemo use. Will the data support broad use or a more selective approach?
- Is adjuvant IO the best path forward?
While ATOMIC may take the lead, the NICHE trials have already sparked interest in neoadjuvant IO, with NEOSHOT and AZUR-2 now exploring neoadjuvant and perioperative strategies. Will adjuvant IO serve as a stopgap until more data emerge, or secure its place through first-mover advantage?
Why It Matters
These trials don’t just add data, they signal progress in the field. They highlight the value of strong lifecycle management as assets move earlier, demonstrate how biomarker-driven strategies can deliver in practice, and lay the groundwork for new care standards that reset competitive dynamics and challenge brand teams to adapt.
At Beyond Blue, our team is closely tracking these developments and helping translate them into strategic clarity.
Want to talk about what these shifts mean for your brand? Let’s connect.
Paula Coyle | p.coyle@beyondblueinsight.com
Lindsay Widger | l.widger@beyondblueinsight.com
Siobhan Davies | s.davies@beyondblueinsight.com
Abstracts discussed:
- DESTINY-Breast09 (LBA1008): Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results.
- SERENA-6 (LBA4): Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind, ctDNA-guided trial.
- ASCENT-04/KEYNOTE-D19 (LBA109): Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 study.
- ATOMIC (LBA1): Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III deficient DNA mismatch repair (dMMR) colon cancer (Alliance A021502).