KEY TAKEAWAYS
- The LCMC3 trial is a phase 2 multicenter trial that tested the safety and efficacy of neoadjuvant atezolizumab and surgery in patients with resectable NSCLC.
- The trial aimed to determine the significant pathological response rate in patients without EGFR/ALK alterations who received neoadjuvant atezolizumab followed by surgery.
- The primary pathological response rate was 20%, and the pathological complete response rate was 6% in patients without EGFR/ALK+ alterations who underwent surgery.
- The study suggests that immune checkpoint inhibitors, such as atezolizumab, may have a role as preoperative therapy in resectable NSCLC and further development is warranted.
There has been no significant improvement in patient outcomes with multimodality treatment for resectable non-small cell lung cancer. However, small clinical trials for resectable non-small cell lung cancer have shown that preoperative treatment with immune checkpoint inhibitors is promising. This large, multicenter study evaluated the effectiveness and safety of neoadjuvant atezolizumab combined with surgery. According to the Eastern Cooperative Oncology Group, patients were considered for enrollment if they had resectable non-small cell lung cancer (stage IB to select IIIB) and a performance status of 0 or 1.
Patients were treated with resection after two cycles of atezolizumab (1,200 mg IV every 3 weeks). Patients without EGFR/ALK+ alterations who showed a primary pathological response were considered successful. Biospecimens and imaging data (CT/PET, pulmonary function tests, etc.) were collected before and after treatment. The v.4.0 version of the Common Terminology Criteria for Adverse Events was used for logging any problems that arose.
About 801 were enrolled between April 2017 and February 2020. At the outset, the demographics were as follows: mean age, 65.1% female; nonsquamous histology, 62%; clinical stages IIB-IIIB, 81%; and 147/181 patients. Among surgical patients who did not have EGFR/ALK alterations, the rates of primary pathological response and complete pathological response were 20% (29/143; 95% confidence interval, 14-28) and 6% (8/143; 95% confidence interval, 2-11) respectively. Before surgery, there were no treatment-related adverse events in grades 4 or 5. Pathologic complete resection was achieved in 145 (91%) of the 159 patients (87.8%) who underwent surgery. There were no deaths during surgery, but two deaths within 90 days afterward, and one was related to the treatment. No established medians for time spent disease-free or overall survival have been made. Atezolizumab was well tolerated, resulted in a 20% central pathological response rate, and permitted safe, complete surgical resection in patients with stage IB to IIIB non-small cell lung cancer who were candidates for curative lobectomy. These findings strongly support preoperative therapy with immune checkpoint inhibitors in locally advanced non-small cell lung cancer.
Source: https://pubmed.ncbi.nlm.nih.gov/36369159/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02927301
Rusch VW, Nicholas A, Patterson GA, Waqar SN, Toloza EM, Haura EB, Raz DJ, Reckamp KL, Merritt RE, Owen DH, Finley DJ, McNamee CJ, Blasberg JD, Garon EB, Mitchell JD, Doebele RC, Baciewicz F, Nagasaka M, Pass HI, Schulze K, Johnson A, Bunn PA, Johnson BE, Kris MG, Kwiatkowski DJ, Wistuba II, Chaft JE, Carbone DP, Lee JM. Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non-small cell lung cancer. J Thorac Cardiovasc Surg. 2022 Oct 8:S0022-5223(22)01055-8. doi: 10.1016/j.jtcvs.2022.10.007. Epub ahead of print. PMID: 36369159.
