A 45 percent reduction in the risk of disease progression
For patients whose lung tumors carry a doubly difficult genetic signature — EGFR mutations compounded by tumor suppressor gene alterations — medicine has long offered no clear path forward. A global Phase III trial now changes that, demonstrating for the first time that pairing the oral drug aumolertinib with conventional chemotherapy can meaningfully delay disease progression in this vulnerable population. The ACROSS 2 trial, presented at the world's leading lung cancer conference, does not yet answer whether patients will live longer overall, but it offers something that did not exist before: a standard of care where there was none.
- Patients with EGFR-mutated lung cancer compounded by tumor suppressor mutations have faced a clinical void — no established treatment, no clear guidance, and a prognosis worse than their peers.
- The ACROSS 2 trial enrolled 1,200 patients across multiple countries to directly confront this gap, testing whether adding chemotherapy to a targeted oral drug could outperform the targeted drug alone.
- The combination therapy extended median progression-free survival from 16.53 to 19.78 months — a three-month gain that represents a statistically significant 45% reduction in the risk of disease progression.
- Side effects were serious but expected, with no new safety signals emerging from the combination, suggesting the approach is tolerable alongside its measurable benefit.
- Overall survival data remains immature, leaving the question of whether patients actually live longer still open — the trial's true legacy will depend on what those numbers eventually reveal.
A three-year clinical trial has produced the first evidence that combining an oral targeted therapy with traditional chemotherapy can meaningfully extend survival in a particularly difficult-to-treat form of lung cancer. The results, presented at the International Association for the Study of Lung Cancer's annual conference, offer a first foothold of hope to patients whose tumors carry a genetic profile that has historically left them without a clear treatment path.
The ACROSS 2 study focused on patients with advanced non-small cell lung cancer whose tumors harbored both EGFR sensitizing mutations and additional mutations in tumor suppressor genes — a combination that typically signals a worse prognosis than EGFR mutations alone. Researchers randomly assigned 1,200 patients across multiple countries to receive either aumolertinib, a third-generation oral EGFR inhibitor, combined with carboplatin and pemetrexed chemotherapy, or aumolertinib alone.
After a median follow-up of just over two years, the combination approach showed a clear advantage: 19.78 months of median progression-free survival versus 16.53 months for monotherapy — a 45 percent reduction in the risk of disease progression that crossed the threshold for clinical meaningfulness. The safety profile remained manageable, with side effects consistent with what is expected from this class of drugs, and no new safety signals emerged from the combination.
What elevates this finding beyond its numbers is what it represents structurally: the first evidence-based standard of care for a patient population that previously had none. Whether the combination ultimately extends lives — not just delays progression — remains an open question, as overall survival data has not yet matured. That longer-term picture will determine whether ACROSS 2 reshapes the standard of care or simply opens a door that further research must walk through.
A three-year clinical trial has produced the first evidence that combining an oral cancer drug with traditional chemotherapy can meaningfully extend survival in a particularly difficult-to-treat form of lung cancer. The results, presented this week at the International Association for the Study of Lung Cancer's annual conference, offer hope to patients whose tumors carry a specific genetic signature that has historically left them without a clear treatment path.
The study, called ACROSS 2, enrolled patients with advanced non-small cell lung cancer whose tumors harbored EGFR sensitizing mutations—a genetic marker that makes the cancer responsive to targeted drugs—along with additional mutations in tumor suppressor genes. This combination of mutations typically signals a worse prognosis than EGFR mutations alone. Until now, doctors had no established standard of care for this population, though earlier research suggested that pairing a targeted drug with chemotherapy might work better than either approach alone.
Researchers randomly assigned patients to one of two treatment paths. One group received aumolertinib, an oral third-generation EGFR inhibitor, at 110 milligrams daily combined with carboplatin and pemetrexed chemotherapy administered every three weeks. The other group received aumolertinib alone. The trial followed 1,200 patients across multiple countries in an open-label design, meaning both doctors and patients knew which treatment they were receiving. The primary measure of success was how long patients' cancer remained stable before progressing.
After a median follow-up of just over two years, the results showed a clear advantage for the combination approach. Patients receiving aumolertinib plus chemotherapy experienced a median progression-free survival of 19.78 months, compared to 16.53 months for those on aumolertinib alone. That three-month difference translates to a 45 percent reduction in the risk of disease progression—a statistically significant finding that crossed the threshold for clinical meaningfulness. Dr. Jie Wang of China's National Cancer Center, who presented the findings, noted that this represents the first global Phase III trial to systematically test this question in this patient population.
The safety profile remained manageable. The most common side effects—occurring in at least one in five patients—included drops in white blood cells, neutrophils, and platelets, along with anemia, liver enzyme elevation, muscle enzyme elevation, kidney function changes, nausea, constipation, and rash. These are largely expected consequences of chemotherapy and the targeted drug combination. Importantly, adding chemotherapy did not introduce new safety signals or fundamentally alter how aumolertinib behaved in the body.
What makes this finding significant is not just the survival extension itself, but the fact that it establishes a first standard treatment for a group of patients who previously had none. Oncologists treating lung cancer patients with this particular genetic profile now have evidence-based guidance. The overall survival data—whether patients actually live longer, not just whether their cancer progresses more slowly—remains immature and will require additional follow-up. That longer-term picture will ultimately determine whether this combination becomes the new standard of care or remains one option among several.
Notable Quotes
This Phase III trial provides the first evidence that aumolertinib combined with platinum-pemetrexed offers a statistically significant PFS benefit over monotherapy for this patient population, with a manageable safety profile.— Dr. Jie Wang, National Cancer Center, China
The Hearth Conversation Another angle on the story
Why does this particular combination of mutations matter so much? Why not just treat everyone with EGFR mutations the same way?
Because EGFR mutations alone respond well to targeted drugs like aumolertinib. But when you add tumor suppressor gene mutations on top of that, the cancer becomes more aggressive and harder to control. It's like the cancer has a backup plan. These patients historically did worse, and doctors didn't know what to do differently for them.
So this trial is saying chemotherapy, which we've used for decades, actually helps a newer targeted drug work better?
Exactly. It seems counterintuitive, but yes. The targeted drug alone wasn't enough for this subset. Adding chemotherapy—hitting the cancer from two different angles—extended the time before the cancer started growing again by about three months on average.
Three months doesn't sound like much. Is that really meaningful?
In cancer treatment, it depends on context. A 45 percent reduction in progression risk is statistically solid. But you're right to push back—we don't yet know if patients actually live longer overall. That data is still being collected. Three months of extra stable disease might mean three months of better quality of life, or it might mean something more. We'll know more when the survival data matures.
What about the side effects? Chemotherapy is notoriously hard on the body.
The side effects were what you'd expect from chemotherapy—low blood counts, nausea, kidney and liver changes. The important finding was that adding chemotherapy didn't create new problems or make aumolertinib behave differently. It was manageable, which matters because if the toxicity had been severe, the benefit wouldn't have been worth it.
Who benefits most from knowing this?
Patients with this specific genetic profile—EGFR mutations plus tumor suppressor mutations—finally have a clear treatment path. And their doctors now have evidence to guide that conversation. Before this trial, there was no standard. Now there is.