You Need to Take a Closer Look at this Targeted Therapy for Lung Cancer

If you treat early-stage non-small cell lung cancer (NSCLC), you’re likely familiar with osimertinib. The targeted therapy has become a cornerstone after surgery for patients with EGFR-positive tumors—particularly those with stage IB or higher.

But new research out of the 2025 annual conference of the American Society of Clinical Oncologists (ASCO) begs the question: Should we be starting osimertinib even earlier?

For years, adjuvant osimertinib (with or without chemo) has been the go-to post-op approach for eligible EGFR+ patients.

But the neoadjuvant landscape—what we do before surgery—has been far murkier. Immunotherapy isn’t effective for EGFR-mutant tumors, so we’ve largely relied on chemo alone.

Until now, there hasn’t been any solid data on whether targeted therapy before surgery actually helps. That changed at ASCO 2025.

What's new and exciting

New data presented shows that neoadjuvant osimertinib has real promise.

In a randomized phase 3 trial, over 350 patients with stage II to IIIB EGFR+ NSCLC (resectable) were assigned to one of three groups: ^[]

• Osimertinib plus chemo

• Osimertinib alone

• Chemo alone

The primary endpoint? Major pathologic response (MPR)—defined as less than 10% viable tumor remaining at surgery.

Here’s what researchers found:

• MPR rates:

  • Osimertinib (± chemo): ~25%

  • Chemo alone: 2%

• Nodal downstaging:

  • Osimertinib: >50%

  • Chemo alone: ~20%

Add osimertinib before surgery, and you’re more likely to see smaller tumors and cleaner nodes in the OR.

What this could mean for oncologists

This study could mark a turning point in how oncologists approach resectable EGFR+ NSCLC. While adjuvant osimertinib remains the only strategy with proven survival benefit, these neoadjuvant results introduce a compelling new consideration: Can we intervene even earlier and improve long-term outcomes?

For oncologists, this might translate to:

• More nuanced, individualized treatment sequencing—especially in patients with bulky nodal disease or high tumor burden.

• Multidisciplinary planning earlier in the pathway, involving at least surgery and medical oncology from the start.

• Potential for new clinical trial enrollment strategies that stratify patients based on molecular subtype and pathologic response.

• Rethinking neoadjuvant therapy as a potential way to improve surgical outcomes—not just to downstage tumors—but with the understanding that its ultimate impact on outcomes is still being studied.

It also raises questions worth chewing on: Will future trials show that neoadjuvant plus adjuvant osimertinib is superior to either alone? Should patients be re-staged post-op to assess further targeted therapy needs?

For some patients, Dr. Singhi advises: "If you have resected EGFR positive lung cancer, specifically an EGFR exon 19 deletion or L858R mutation, and you're being considered for a treatment before surgery, you should talk to your care team about treatment with osimertinib with or without chemo."

That said, adjuvant osimertinib remains the standard of care, and survival data for neoadjuvant use is still pending. But oncologists may now want to begin viewing the pre-op window as an opportunity—not just a holding pattern. And if future data confirm long-term survival benefits? It could change the entire treatment playbook.