ADCs step into first-line mBC
ASCO 2025 highlighted the growing role of ADCs in reshaping metastatic breast cancer treatment. Two key trials, DESTINY-Breast09 and ASCENT-04, showed strong efficacy for ADCs in 1L HER2+ mBC and PD-L1+ TNBC respectively, raising the prospect of moving beyond traditional chemotherapy. But each enters a very different clinical context: one marked by urgency, the other by sequencing complexity.
ASCENT-04: Addressing a clear need in TNBC
Trodelvy showed compelling activity with pembrolizumab in 1L PD-L1+ TNBC. In addition, any concerns about toxicity were settled, given that the median treatment duration was longer with Trodelvy + pembro (vs. TPC + pembor), and grade 3/4 adverse event rates were similar between the two arms. Given that many TNBC patients never reach second-line therapy, there is a clear case for using the most effective treatment up front, and Trodelvy is expected to become standard of care.
DESTINY-Breast09: A strong result, but with questions
Enhurtu showed impressive efficacy in 1L HER2+ mBC with pertuzumab vs. SoC THP (mPFS 40.7 mo vs. 26.9 mo, HR 0.56). However, in a setting where multiple lines of therapy are expected (and Enhurtu is already established later), HCPs seek clarity on where, and how, to use. There is growing interest in using Enhertu as induction therapy, rather than until progression (as tested), but without data to support that approach, treatment duration may remain a sticking point.
ER+ mBC evolves: PROTACs join the expanding SERD field
ASCO 2025 delivered key updates in the evolving field of ER-targeted therapy. First-line data for camizestrant (SERENA-6) and the first phase III data for a PROTAC (VERITAC-2) drew attention, pushing personalisation earlier and raising questions around what will define the next standard.
Camizestrant makes its move in 1L ER+ mBC
SERENA-6 showed that switching from an aromatase inhibitor to camizestrant upon detection of an ESR1 mutation resulted in a 38% risk reduction in progression or death. The study supports a shift toward real-time, mutation-guided therapy, though broader adoption will hinge on overcoming logistical and psychological barriers to routine testing. At the same time, camizestrant becomes the first oral SERD to show benefit in 1L ER+ mBC, staking its claim in what’s set to become a highly competitive first-line space.
PROTACs enter the line up
Vepdegestrant demonstrated a 2.9-month PFS benefit over fulvestrant in ESR1-mutant patients, mirroring gains seen with oral SERDs. With efficacy unlikely to be a clear differentiator, attention turns to tolerability. Early signs point to a more favourable GI toxicity profile, often a class effect of SERDs. However, even with this edge, vepdegestrant may struggle for space as oral SERDs move earlier in treatment.
Expanding IO use across early-stage cancers
ASCO 2025 reinforced immunotherapy’s growing role across early-stage cancers, with notable wins from ATOMIC, MATTERHORN, and NIVOPOSTOP. These data extend the trend seen in NSCLC, melanoma, and TNBC, confirming that IO given with curative intent, whether neoadjuvantly, adjuvantly, or perioperatively, can improve outcomes.
However, in some settings, such as stage III dMMR colon cancer* and HNSCC, these trials build on an existing body of evidence and add yet more ways to integrate IO. The question shifts from whether to use IO to how and when, and treatment planning is becoming increasingly nuanced.
- With limited data to guide decisions, physicians continue to rely on scientific rationale and cross-indication insights to guide decisions, SWOG S1801 remains a key reference.
- Multidisciplinary decision-making is becoming essential, factoring in disease, tumor, and patient characteristics.
- Tools such as pCR, MPR, and ctDNA clearance are also gaining traction to inform adjuvant therapy desicions.
For the pharmaceutical industry, the opportunity lies not only in generating positive data, but in enabling confident, risk-adapted treatment strategies in this increasingly complex landscape.
ES-SCLC: Progress gains traction
After decades of limited progress, a meaningful shift is well underway in the management of extensive-stage small cell lung cancer (ES-SCLC). ASCO 2025 highlighted important advances across treatment lines, while also showcasing a pipeline rich with promise, from tri-specific T-cell engagers to B7-H3 ADCs.
1L: Lurbinectedin moves into maintenance
Phase III IMforte data demonstrated that adding lurbinectedin to atezolizumab maintenance therapy significantly improves PFS and OS. However, the added benefit comes with increased toxicity, thus requiring thoughtful patient selection.
2L: Tarlatamab poised to cement its role
Confirmatory Phase III data from DeLLphi-304 reaffirm tarlatamab’s potential as a new second-line standard of care. Although the data remain immature, the median OS reached 13.6 months compared to 8.3 months with chemotherapy. Future success for tarlatamab may rest on:
- Implementation support – with ASCO sessions focusing heavily on the practicalities of safe and scalable outpatient administration.
- Strategic positioning – while movement into earlier lines is anticipated, the smaller efficacy gains seen in DeLLphi-304 vs. 301 (a heavily pre-treated population) may suggest the drug’s strongest impact lies in later lines.
Precision, personalisation, and positioning: biomarkers take centre stage
As pipelines expand and treatment options multiply, one message from ASCO 2025 was clear: the importance of personalising cancer care is only growing. Physicians increasingly rely on biomarkers for precise treatment guidance: who benefits most, who may need treatment intensification, who is at risk of harm, and whether treatment can be tailored over time.
AI-informed platforms were presented across multiple tumor types, improving prognostication, more reliably detecting hard-to-define groups (e.g. HER2-ultralow), and
surfacing emerging biomarkers such as TROP2-NMR. These tools promise richer segmentation but also raise questions around implementation and trust.
ctDNA also continued its steady advance, not just for prognostic value but as a real-time tool to inform escalation and de-escalation strategies. Whether used in early-stage settings to refine adjuvant decisions or in advanced disease to identify resistance, ctDNA is helping shift cancer care from fixed to flexible.
Beyond the tools: while new tools captured attention, established assets also reminded us of the strategic value of biomarker analysis. Exploratory biomarker analysis for DESTINY-Breast06, dissecting efficacy for Enhurtu across patients with PIK3CA, AKT, and ESR1 mutations, reinforced the brand’s position in an increasingly competitive landscape. In this next phase of precision oncology, biomarkers are becoming just as critical to maintaining relevance as they are to unlocking new opportunity.
What it all means for oncology brands today
As treatment options expand and the oncology landscape evolves rapidly, maintaining strategic focus is more important than ever. As we return to supporting pharma clients, we’re keeping these key priorities in mind:
Helping physicians make the call: There is a clear demand for biomarkers to inform patient selection, to assist in identifying better responders/predict toxicity.
Simplifying sequencing: With more options available, especially within tx. class (e.g. ADCs, RLTs), making sense of how best to sequence therapies is a clear priority.
Facilitating adoption: Understand the full patient journey and context to support brands circumvent logistical/infrastructure barriers to adoption.
Backing up early use: Earlier treatment sounds promising, but HCPs are often grappling with the loss of a much-needed later line option and therefore having the right evidence is key.
Redefining ‘manageable’: As the patient voice increasingly moves to the forefront, PROs are crucial to understanding what trade-offs feel acceptable in real life.
Our team is always up for a conversation on the latest clinical developments and what they mean for pharma strategy. If you’d like to discuss we’d love to hear from you. Get in touch.
*ATOMIC represents the first randomised phase III showing a benefit of IO in stage III dMMR colon cancer but previous phase II trials have shown a role for neoadjuvant IO