The Phase 3 study of osimertinib as neoadjuvant therapy for EGFRm positive resectable non-small cell lung cancer reached primary completion on 2024-10-15. Results indicate that osimertinib, both as monotherapy and in combination with chemotherapy, significantly improved major pathological response rates, with osimertinib plus chemotherapy achieving a 25.6% Major Pathological Response (MPR) compared to 1.7% for chemotherapy alone.
Background
This study investigated osimertinib (Tagrisso) as a neoadjuvant therapy for patients with EGFRm positive resectable non-small cell lung cancer (NSCLC). The trial compared osimertinib as monotherapy or in combination with chemotherapy against standard-of-care chemotherapy alone.
Trial design
The Phase 3, randomized, controlled, 3-arm, multi-centre study (NCT04351555) enrolled 358 participants with EGFRm positive resectable non-small cell lung cancer. The study evaluated neoadjuvant osimertinib as monotherapy or in combination with chemotherapy, versus standard-of-care chemotherapy alone. Interventions included osimertinib, cisplatin, carboplatin, placebo, and pemetrexed.
Key results
The trial reported the following major pathological response (MPR) and pathological complete response (pCR) rates:
- For Major Pathological Response (MPR) by IASLC Method:
- Osimertinib + Chemo arm: 25.6% of participants.
- Osimertinib monotherapy arm: 24.8% of participants.
- Placebo + Chemo arm: 1.7% of participants.
- For Major Pathological Response (MPR) by Chemotherapy Method:
- Osimertinib + Chemo arm: 24.8% of participants.
- Osimertinib monotherapy arm: 20.5% of participants.
- Placebo + Chemo arm: 1.7% of participants.
- For Pathological Complete Response (pCR) by IASLC Method:
- Osimertinib + Chemo arm: 4.1% of participants.
- Osimertinib monotherapy arm: 8.5% of participants.
- Placebo + Chemo arm: 0% of participants.
- For Pathological Complete Response (pCR) by Chemotherapy Method:
- Osimertinib + Chemo arm: 4.1% of participants.
- Osimertinib monotherapy arm: 8.5% of participants.
- Placebo + Chemo arm: 0% of participants.
Key analyses showed significant differences:
- A Cochran-Mantel-Haenszel analysis yielded an Odds Ratio (OR) of 19.82 (95% CI: 4.6-85.32) with a p-value of 0.0001.
- Another Cochran-Mantel-Haenszel analysis showed an Odds Ratio (OR) of 19.28 (95% CI: 4.56-81.63) with a p-value of 0.0001.
- A further Cochran-Mantel-Haenszel analysis reported an Odds Ratio (OR) of 19.17 (95% CI: 4.45-82.66) with a p-value of 0.0001.
- Another Cochran-Mantel-Haenszel analysis indicated an Odds Ratio (OR) of 14.68 (95% CI: 3.46-62.28) with a p-value of 0.0001.
- Fisher Exact tests yielded p-values of 0.0599 and 0.0007.
What this means
The results from this Phase 3 study suggest that osimertinib, both as monotherapy and in combination with chemotherapy, significantly improves pathological response rates in patients with EGFRm positive resectable non-small cell lung cancer when used as neoadjuvant therapy. The substantial increase in Major Pathological Response (MPR) and Pathological Complete Response (pCR) rates compared to chemotherapy alone indicates a potential benefit for these patients. The highly significant p-values from the statistical analyses further support the efficacy of osimertinib in this setting. These findings could lead to new treatment strategies for this patient population, potentially improving surgical outcomes and long-term prognosis.
Source
The information regarding the primary completion of this trial and its 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 Resect", were posted on 2024-10-15 on clinicaltrials.gov.