Research presented at the AACR Annual Meeting 2023 revealed a potential new standard of care for non-small cell lung cancer (NSCLC) and highlighted other treatments that demonstrated early activity in NSCLC and extensive stage small-cell lung cancer (ES-SCLC).
Results from the phase 3 AEGEAN trial suggested that perioperative durvalumab and neoadjuvant chemotherapy may be a new standard of care for treatment-naïve adults with resectable NSCLC.1
In the phase 2 MATCH trial, patients with treatment-naïve ES-SCLC had a high disease control rate after receiving low-dose radiotherapy, atezolizumab, and chemotherapy.2
In another phase 2 trial, maintenance treatment with rucaparib and nivolumab after frontline chemotherapy demonstrated activity in patients with platinum-sensitive ES-SCLC.3
A third phase 2 trial showed that frontline surufatinib and toripalimab produced durable responses in patients with advanced, PD-L1-positive NSCLC.4
AEGEAN: Perioperative Durvalumab Plus Chemo May Be New Standard Care
Durvalumab and chemotherapy followed by surgery and adjuvant durvalumab produced better outcomes than neoadjuvant chemotherapy and surgery alone in treatment-naïve adults with resectable NSCLC who were enrolled in the AEGEAN trial (ClinicalTrials.gov Identifier: NCT03800134).1
This double-blind, phase 3 trial enrolled patients with stage IIA-IIIB (N2) NSCLC. The patients were randomly assigned to receive durvalumab or placebo, each in combination with 4 cycles of platinum-based chemotherapy. For patients with non-squamous NSCLC, chemotherapy consisted of cisplatin/carboplatin and pemetrexed. Patients with squamous NSCLC received carboplatin plus paclitaxel or cisplatin/carboplatin plus gemcitabine.
Patients in the durvalumab arm received 1500 mg of durvalumab every 3 weeks for 4 cycles, and patients in the control arm received placebo. This was followed by surgery and further treatment with durvalumab or placebo every 4 weeks for up to 12 cycles.
After excluding patients with EGFR or ALK mutations, the efficacy analysis included 740 patients — 366 in the durvalumab arm and 374 in the placebo arm. Baseline characteristics were generally well balanced between the arms.
Most patients in the durvalumab and placebo arms completed 4 cycles of chemotherapy (84.7% and 87.2%, respectively) and 4 cycles of either durvalumab or placebo (86.9% and 88.5%). Most patients underwent surgery (80.6% and 80.7%, respectively) and had R0 resections (94.7% and 91.3%, respectively).
The trial met its primary endpoints, with durvalumab showing significant improvements in pathologic complete response (pCR) and event-free survival (EFS) compared to placebo.
The pCR rate was 17.2% in the durvalumab arm and 4.3% in the placebo arm (P =.000036). At a median follow-up of 11.7 months, the median EFS had not been reached in the durvalumab arm and was 25.9 months in the placebo arm (hazard ratio, 0.68; 95% CI, 0.53-0.88; P =.004).
“The data show that patients receiving durvalumab on this study had a 32% lower chance of experiencing disease recurrence, progression events, or death,” said study presenter John V. Heymach, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
The safety analysis included 400 patients in the durvalumab arm and 399 in the placebo arm. The rate of adverse events (AEs) possibly related to treatment was 86.5% in the durvalumab arm and 80.7% in the placebo arm. The rate of grade 3-4 AEs possibly related to treatment was 32.3% and 33.1%, respectively.
Fatal AEs occurred in 7 patients in the durvalumab arm and 2 in the placebo arm. In the durvalumab arm, the causes of death were interstitial lung disease (n=2), immune-mediated lung disease (n=1), pneumonitis (n=1), hemoptysis (n=1), myocarditis (n=1), and decreased appetite (n=1). In the placebo arm, the causes of death were pneumonia (n=1) and infection (n=1).
“This study suggests that perioperative durvalumab may offer significant benefits for patients, and if the AEGEAN regimen receives regulatory approval, it could become a new standard of care for resectable NSCLC,” Dr Heymach said. “We look forward to seeing future data updates as this study continues.”
“The AEGEAN findings confirm the benefits of neoadjuvant immunotherapy and the essential role of immunotherapy in the setting of early lung cancer and challenge the concern that neoadjuvant therapy could delay surgery or render patients ineligible for resection,” said Tércia Reis, MD, of Grupo Oncoclinicas in Salvador, Brazil, who was not involved in this study.