One in Five Alive at Five Years: What HIMALAYA's Landmark Long-Term Data Mean for Liver Cancer

When I discuss advanced liver cancer with a patient for the first time, one of the hardest parts of the conversation has always been talking about long-term survival, because until recently, we simply did not have five-year data from a large randomized trial to point to. That changed with an update from the HIMALAYA trial, which this year became the first Phase 3 study in unresectable hepatocellular carcinoma (HCC) to report a full five-year overall survival analysis — and the results give me something genuinely new to tell my patients.

HIMALAYA tested a treatment approach known as STRIDE: a single "priming" dose of tremelimumab, an antibody that blocks the CTLA-4 checkpoint, combined with regular doses of durvalumab, which blocks the PD-L1 checkpoint. Both drugs work by removing the brakes the immune system's own regulatory checkpoints place on the body's ability to recognize and attack cancer cells, essentially giving the immune system permission to fight the tumor. The trial compared STRIDE against sorafenib, which for over a decade was the standard first-line systemic treatment for unresectable HCC and remains an important benchmark against which every newer therapy is measured.

The headline result from this five-year update is striking in its simplicity: 19.6 percent of patients treated with STRIDE were alive at five years, compared to 9.4 percent of patients treated with sorafenib. Put another way, roughly one in five patients on the STRIDE regimen remained alive five years after starting treatment, compared to roughly one in ten on sorafenib — essentially doubling the proportion of long-term survivors. Just as important from a safety standpoint, the update reported no new, late-onset serious side effects with continued follow-up, meaning the durability of the benefit did not come at the cost of accumulating toxicity over time.

I want to explain why this milestone matters beyond the raw numbers. Historically, systemic treatment for advanced liver cancer offered modest gains measured in weeks to a few months of extra survival, and clinicians rarely spoke in terms of five-year outcomes at all for this disease — that language was reserved for early-stage, surgically treated liver cancer. HIMALAYA's five-year data mark one of the first times we can honestly tell a subset of patients with unresectable liver cancer that long-term survival, even something approaching what some might loosely call durable disease control, is now a realistic possibility for a meaningful minority, not a statistical rounding error.

It is also worth noting what makes the STRIDE regimen distinctive within the growing field of liver cancer immunotherapy. Unlike combination regimens that pair a checkpoint inhibitor with a targeted anti-angiogenic drug (an approach used in other approved liver cancer treatments), STRIDE combines two immune checkpoint inhibitors with different mechanisms, using a single tremelimumab dose upfront to "prime" the immune response before switching to maintenance durvalumab. This design appears to allow the immune system to mount a more sustained anti-tumor response in some patients, which the five-year data seem to support.

None of this diminishes the seriousness of an unresectable HCC diagnosis. The majority of patients on both arms of this trial did not reach the five-year mark, and liver cancer remains a disease where outcomes depend heavily on how well the underlying liver disease — whether from hepatitis B, hepatitis C, alcohol-related liver disease, or increasingly, metabolic dysfunction-associated steatotic liver disease (MASLD) — is also being managed alongside the cancer itself. Liver function at diagnosis, tumor burden, and vascular invasion all still meaningfully affect which patients are most likely to benefit.

What this update does give me, as someone who has these conversations regularly, is a foundation of real data rather than extrapolation when patients ask the question every patient eventually asks: "If this works, how long could I actually have?" For the first time in a Phase 3 trial of this disease, I can answer with an actual five-year survival curve rather than a projection. That is a meaningful shift, and I expect STRIDE-based approaches will continue to expand their role in how we sequence treatment for unresectable liver cancer going forward.

Source: HIMALAYA trial five-year overall survival update (STRIDE regimen: tremelimumab plus durvalumab), Journal of Hepatology, with results also presented via ASCO; original trial sponsored by AstraZeneca.