ASCO 2026: Translating oncology innovation into real-world impact

ASCO 2026 delivered no shortage of headline-making data, positive trials and new strategies across tumor types, much of it genuinely practice-changing.  But treatment efficacy in a trial is only the first thing worth knowing.  What comes after matters just as much: who will benefit most, when it should be used, how it fits into an evolving landscape, and whether those results hold up to the patient sitting across from you.

That challenge was reflected in ASCO's 2026 theme, "The science and practice of translation: improving cancer outcomes worldwide."  The meeting showcased important scientific advances. But as an oncologist, I know that whether a treatment works in a trial is rarely where the questions end. Many of the most consequential conversations centered on implementation: how physicians, researchers, and health systems will turn promising clinical evidence into better decisions and outcomes for patients. 

Three developments stood out to me - not only for their scientific significance, but for the questions I expect they’ll raise as they move from the trial  setting into real-world care.

  The RAS revolution

The headliner at the conference was daraxonrasib, the first multi-selective RAS(ON) inhibitor - meaning it targets RAS proteins in their active, GTP-bound state - for previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). For decades, the RAS pathway was oncology’s archetypal “undruggable” target. KRAS G12C inhibitors like sotorasib and adagrasib chipped away at that reputation, but they only hit a single mutation. Daraxonrasib is different. In the phase 3 RASolute 302 trial, once-daily oral daraxonrasib nearly doubled median overall survival versus standard chemotherapy (13.2 vs 6.6 months; HR 0.40), with fewer severe adverse events.

For a disease that has humbled oncology for decades, those numbers deserve the standing ovation they drew at the Plenary. The potential significance of this breakthrough extends beyond the study population: by validating multi-selective RAS(ON) as a broad therapeutic platform, daraxonrasib opens the door for other RAS-driven tumors, including colorectal cancer and NSCLC. The translation question this study raises isn’t whether the drug works - it plainly does - but how quickly the paradigm scales. That is a question of trial design and real-world deployment, as much as biology.

Two trials at this year's meeting stood out not just for their results, but for what they represent together: a field that is increasingly asking whether we can treat earlier, with curative intent, and spare patients the burden of relapse.

In the phase 3 PROTEUS trial, patients with high-risk localized or locally advanced prostate cancer receiving apalutamide combined with androgen-deprivation therapy (ADT) six months before and after radical prostatectomy had improved five year metastasis-free survival (78.2% vs 73.5%; HR 0.80), along with a roughly nine-fold increase in a complete pathological response or minimal residual disease compared to patients receiving ADT, not radical prostatectomy alone. For a group where half of patients still relapse within five years despite surgery, that's a meaningful shift, and this perioperative regimen has real potential to change long-term outcomes.

In NSCLC, the phase 3 LIBRETTO-432 trial showed adjuvant selpercatinib delivering a striking improvement in 24-month event-free survival (92% vs. 61% with placebo; HR 0.17) for patients with early-stage RET fusion–positive disease. RET fusions are found in only 1-2% of NSCLC cases, but for those patients, these results are transformative, and they strengthen the case - already made by EGFR and ALK - for comprehensive molecular testing at diagnosis. Yet a result like this only helps a patient whose tumor is actually tested, and in the real world, biomarker testing in early-stage NSCLC still trails the metastatic setting. Selpercatinib works; the next question is whether the patient who needs it will be identified at the right time.

Taken together, these trials reflect a theme that has been building for several years now: targeted therapies and novel combinations moving into earlier, potentially curative settings. And it changes how we have to think about these drugs. In the palliative setting, the goal is to extend life. Here, we're talking about something more — not just living longer, but living better. Survivorship, once an afterthought in diseases like NSCLC, is now part of the conversation.

The HARMONi-6 trial demonstrated that ivonescimab, a first-in-class bispecific antibody, combined with chemotherapy significantly improved overall survival compared to tislezlizumab - a standard regimen in China - for patients with previously untreated advanced squamous NSCLC (median OS 27.9 vs 23.7 months; HR 0.66).

Notably, both the drug and trial originated in China, which now registers more clinical trials than any other country - no longer, to paraphrase a recent report from the US National Bureau of Economic Research, “a free rider and peripheral adopter of existing therapies”, but “a major source of frontier innovation.”

That origin, however, also shapes the evidence. Ivonescimab was tested against tislelizumab, a regional standard, rather than pembrolizumab, the global one - a choice that reflects where the trial was run. The result is genuinely positive, but a win against a regional benchmark doesn’t tell us how ivonescimab would fare against the regimen most oncologists elsewhere actually prescribe - which is why much of the field is waiting on the global head-to-head trials against pembrolizumab now underway.  

The real question: now what?

The breakthroughs presented this year were remarkable, but as ASCO President Eric Small, MD, noted in his presidential address, “discovery alone is not enough. It’s about what becomes of what we discover.” That is the work that starts the moment a trial reads out, and it runs through three connected challenges.

New modalities have been outpacing conventional ones for some time now, and there are so many options in the market today that innovation itself is not always the constraint. Bispecifics are moving from last-resort use in hematologic malignancies into earlier lines and even solid tumors, while antibody-drug conjugates have evolved from a niche format to a crowded field, with multiple agents competing in the same lines of therapy. When multiple programs hit the same target with broadly similar mechanisms, the mechanism itself stops being the differentiator. What separates them is performance - which agent is more effective in which patients, better tolerated, easier to stay on - and increasingly, commercial considerations as well.

Trial populations rarely reflect real-world patients. Once approved, new drugs are invariably used in broader patient populations - with far more diverse biomarkers, comorbidities, and treatment histories than the trial enrolled. How well can I expect a new agent or combination regimen to work for the specific patient in front of me, and where does it belong in their sequence of therapies? These are precisely the questions RWE is designed to answer - and why it has moved from a supplementary consideration to a central one.

HARMONI-6 raised this question directly, but even global studies— such as PROTEUS, spanning 18 countries - must contend with local differences in patient populations and standards of care. My colleague Arun Sujenthiran, MD, recently wrote about why global data matters precisely because it can capture local nuance - how treatments actually perform across different settings, populations, and standards of care.

RWE can close the gap between research and care

Clinical trials establish whether a therapy can work - and as daraxonrasib’s long rod through the “undruggable” wilderness shows, getting there is a real challenge in its own right. But translating those findings into better outcomes at scale, across the diverse patients and health systems where care actually happens, is a second hard problem that is increasingly part of the job to determine whether any of this changes what happens in the clinic room.

That's where real-world evidence has an increasingly important role to play - and why it remains a central focus of our work at Flatiron. As innovation accelerates, connecting clinical trial findings with real-world experience will only become more important.

The science of ASCO 2026 was genuinely exciting. Understanding how those advances translate into everyday care will determine whether they reach the patients they were built for.

If you're interested in learning more, reach out to discuss how Flatiron can support evidence generation across your portfolio.