Perioperative Immunotherapy: A Promising Approach for Resectable Lung Cancer

A regimen of pre-surgical immunotherapy and chemotherapy followed by post-surgical immunotherapy significantly improved event-free survival (EFS) and pathologic complete response (pCR) rates compared to chemotherapy alone in patients with operable non-small cell lung cancer (NSCLC), according to Phase III trial results presented today by researchers from The University of Texas MD Anderson Cancer Centre at the American Association for Cancer Research (AACR) Annual Meeting.

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Durvalumab and Platinum-Based Chemotherapy as Perioperative Treatment of Lung Cancer

The AEGEAN trial looked at durvalumab given perioperatively, which means it was given both before and after surgery. Pre-surgical (neoadjuvant) durvalumab and platinum-based chemotherapy were followed by post-surgical (adjuvant) durvalumab or neoadjuvant placebo and chemotherapy was followed by adjuvant placebo. These are the first findings on the benefits of perioperative immunotherapy for resectable NSCLC, and they add to the expanding body of evidence showing the benefits of both neoadjuvant and adjuvant immunotherapy for these patients.

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Potential to Increase Cures for Lung Cancer

"Our goal is to increase cures for lung cancer. Throughout decades of research with adjuvant and neoadjuvant chemotherapy, we only succeeded in increasing cures by around 5%," said principal investigator John Heymach, M.D., Ph.D., chair of Thoracic/Head & Neck Medical Oncology at MD Anderson. "This one study alone has the potential to increase that percentage significantly, and we look forward to many more improvements going forward."

Patients who received perioperative durvalumab had a 17.2% pCR compared to only 4.3% of those who received chemotherapy alone. The median EFS in the placebo arm was 25.9 months at the first interim analysis, with a median follow-up of 11.7 months, while it had not yet been reached in the durvalumab arm.

When compared to chemotherapy alone, our findings indicate a 32% lower risk of patients experiencing disease recurrence, progression events, or death with immunotherapy-based treatment. When compared to chemotherapy alone, approximately four times as many patients treated with perioperative durvalumab + chemotherapy attained a pCR.

Durvalumab, an immune checkpoint inhibitor that targets PD-L1, was previously licenced for the treatment of patients with biliary tract cancer, liver cancer, small cell lung cancer, and non-small cell lung cancer. Durvalumab is currently used to treat patients with locally advanced, unresectable NSCLC after definitive chemoradiotherapy, as well as patients with metastatic NSCLC when combined with tremelimumab and platinum-based chemotherapy.

Previous trials on resectable NSCLC have shown some benefit from adjuvant or neoadjuvant immunotherapy, but Heymach stated that the advantages have been minimal thus far. MD Anderson has long been involved in multidisciplinary efforts to improve patient outcomes through the use of neoadjuvant therapies. Numerous clinical trials, including the NEOSTAR and NeoCOAST trials, are looking into neoadjuvant immunotherapy and new combinations to eliminate viable tumours before surgery and lower recurrence rates.

The Phase III AEGEAN trial is a randomised, double-blind, placebo-controlled study in adults with untreated stage IIA-IIIB NSCLC to assess the advantages of perioperative durvalumab coupled with platinum-based chemotherapy. A total of 802 patients were randomly assigned to one of two arms. The key outcomes of the trial are pCR, as determined by a central lab, and EFS, as determined by a blinded independent central review.

The adjusted intent-to-treat population excludes patients with EGFR/ALK mutations. The efficacy analysis included 740 individuals, with 366 on the durvalumab arm and 374 on the placebo arm. The median age of participants in each arm was 65, with men accounting for 71.6% of the total. There were 53.6% white patients, 41.5% Asian patients, and 4.9% others.

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Tolerability and Adverse Effects of Perioperative Durvalumab

Overall, the therapies were well tolerated, and the adverse effects were in line with previous research. Maximum grade 3-4 any cause adverse events were seen in 42.3% and 43.4% of participants in the durvalumab and placebo arms, respectively.

The gains in both pCR and EFS were essentially consistent across established patient groupings, and the trial will continue to analyse long-term EFS, disease-free survival, and overall survival outcomes.

Future Directions in Neoadjuvant and Adjuvant Durvalumab Therapy and Patient Selection

"This study shows that a combination of neoadjuvant and adjuvant durvalumab offers benefit for patients and may have the potential to change standard-of-care for patients with resectable non-small cell lung cancer," Heymach said. "Going forward, we face a series of questions about how to build more effective regimens without giving more treatment than is necessary."

Future research must discover which individuals benefit the most from neoadjuvant therapy and may be able to avoid further treatment, as well as those who remain at high risk of recurrence and may require more intensive adjuvant regimens, according to Heymach.

Source-Medindia