Trial results for a Phase 3 study evaluating osimertinib (Tagrisso) as neoadjuvant therapy for EGFRm positive resectable non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2026-06-05. The study demonstrated that osimertinib, both as monotherapy and in combination with chemotherapy, significantly increased Major Pathological Response (MPR) rates compared to chemotherapy alone. For instance, osimertinib plus chemotherapy achieved an MPR of 25.6% (IASLC method), while chemotherapy alone resulted in an MPR of just 1.7%.
Background
This study investigated osimertinib in the neoadjuvant setting for patients with EGFRm positive resectable non-small cell lung cancer (NSCLC). The trial aimed to assess its efficacy when administered before surgery, either as a monotherapy or in combination with standard chemotherapy, compared to chemotherapy alone.
Trial design
The Phase 3 study (NCT04351555) enrolled 358 participants with EGFRm positive resectable non-small cell lung cancer. This multi-centre, randomised, controlled, 3-arm study evaluated neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus standard of care chemotherapy alone. The chemotherapy regimen included cisplatin, carboplatin, and pemetrexed, with a placebo arm for comparison with osimertinib monotherapy.
Key results
The trial reported the following Major Pathological Response (MPR) and Pathological Complete Response (pCR) rates:
- Major Pathological Response (MPR) - IASLC Method:
- Osimertinib + Chemo arm: 25.6% of participants.
- Osimertinib arm: 24.8% of participants.
- Placebo + Chemo arm: 1.7% of participants.
- Major Pathological Response (MPR) - Chemotherapy Method:
- Osimertinib + Chemo arm: 24.8% of participants.
- Osimertinib arm: 20.5% of participants.
- Placebo + Chemo arm: 1.7% of participants.
- Pathological Complete Response (pCR) - IASLC Method:
- Osimertinib + Chemo arm: 4.1% of participants.
- Osimertinib arm: 8.5% of participants.
- Placebo + Chemo arm: 0% of participants.
- Pathological Complete Response (pCR) - Chemotherapy Method:
- Osimertinib + Chemo arm: 4.1% of participants.
- Osimertinib arm: 8.5% of participants.
- Placebo + Chemo arm: 0% of participants.
Key analyses comparing the osimertinib arms to the placebo + chemo arm showed statistically significant differences:
- For MPR (IASLC Method), an Odds Ratio of 19.82 (95.0% CI: 4.6-85.32) was observed, with a p-value of 0.0001.
- For MPR (Chemotherapy Method), an Odds Ratio of 19.28 (95.0% CI: 4.56-81.63) was observed, with a p-value of 0.0001.
- Additional analyses also showed Odds Ratios of 19.17 (95.0% CI: 4.45-82.66) and 14.68 (95.0% CI: 3.46-62.28), both with a p-value of 0.0001.
- For pCR (IASLC Method), a Fisher Exact test yielded a p-value of 0.0007 for one comparison and 0.0599 for another.
What this means
The results indicate that neoadjuvant osimertinib, either alone or in combination with chemotherapy, significantly improves pathological response rates in patients with EGFRm positive resectable non-small cell lung cancer compared to chemotherapy alone. The substantial increase in Major Pathological Response (MPR) and Pathological Complete Response (pCR) rates suggests that osimertinib could play a crucial role in improving outcomes for this patient population prior to surgery. The highly statistically significant p-values (e.g., 0.0001) for the odds ratios underscore the robustness of these findings, highlighting a strong potential benefit for integrating osimertinib into neoadjuvant treatment strategies for resectable EGFRm NSCLC.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04351555, titled "A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer", were posted on 2026-06-05 on clinicaltrials.gov.