Imfinzi (durvalumab) prima e dopo l'intervento chirurgico ha ridotto del 32% il rischio di recidiva, progressione o morte nel carcinoma polmonare non a piccole cellule resecabile (NSCLC)

Positive results from the AEGEAN Phase III trial showed that treatment with AstraZeneca’s Imfinzi (durvalumab) in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) versus neoadjuvant chemotherapy alone followed by surgery for patients with resectable early-stage (IIA-IIIB) non-small cell lung cancer (NSCLC).

The combination of Imfinzi and neoadjuvant chemotherapy also demonstrated a statistically significant and meaningful improvement in pathologic complete response (pCR), a dual primary endpoint, compared to neoadjuvant chemotherapy alone, at a previously reported interim analysis. The final analysis was consistent with these previously announced positive results.

Results will be presented in a plenary session at the American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida (abstract #CT005).

In a planned interim analysis of EFS, patients treated with the Imfinzi-based regimen before and after surgery showed a 32% reduction in the risk of recurrence, progression events or death versus chemotherapy alone (32% data maturity, EFS hazard ratio [HR] of 0.68, 95% confidence interval [CI] 0.53-0.88; p=0.003902). In a final analysis of pCR, treatment with Imfinzi plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of 17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone (difference in pCR 13.0%; 95% CI 8.7-17.6). The trial will continue as planned to assess key secondary endpoints including disease-free survival (DFS) and overall survival (OS).

• Key Takeaways/Potential Implications
  • Neoadjuvant durva + chemo followed by adjuvant durva monotherapy (perioperative IO + chemo) significantly improved both pCR and EFS among patients with resectable early-stage (IIA-IIIB) NSCLC vs neoadjuvant chemo alone
    • This is the first Phase 3 study to describe the benefit of perioperative immunotherapy + neoadjuvant chemotherapy, although it remains unknown how perioperative durva will compare to perioperative pembro in P3 KEYNOTE-671 (results expected at ASCO)
  • Perioperative durva (AEGEAN) showed very similar efficacy for both pCR and EFS in this setting to neoadjuvant nivo alone (CheckMate 816), and thus the adjuvant portion of the regimen is called into question
    • Longer-term follow-up of EFS as well as OS from these studies is likely needed to guide physician decision making
    • Positive EFS data from AEGEAN may support approval of this regimen in resectable NSCLC, but payers may challenge access without seeing an added benefit for the adjuvant component
  • The discussant noted that AEGEAN solidifies IO as a new SOC in early-stage NSCLC as it lends additional data to that of neoadjuvant nivolumab from P3 Checkmate-816
    • However, further investigation is needed to support the rationale of using IO both pre- and post-surgery and to uncover pathologic biomarkers of response to guide perioperative IO treatment vs. neoadjuvant vs. adjuvant therapy in resectable NSCLC patients
  • Study Information
    • AEGEAN (NCT03800134): P3 neoadjuvant durva + chemo followed by adjuvant durva vs. neoadjuvant chemo in resectable Stage IIA-IIIB NSCLC
    • N=825
    • 1EP: EFS, pCR
  • Efficacy (durva + chemo vs. chemo)
    • mEFS (mos): NR vs 25.9 (HR = 0.68)
      • 12-mo EFS: 73% vs 65%
      • 24-mo EFS: 63% vs 52%
    • mEFS HR by PD-L1 expression
      • PD-L1 <1%: HR = 0.76
      • PD-L1 1-49%: HR = 0.70
      • PD-L1 ≥50%: HR = 0.69
    • pCR: 17% vs 4%
    • MPR: 33% vs 12%
  • Safety (durva + chemo vs. chemo)
    • Gr3/4 TRAEs: 32% vs. 33%
      • AEs consistent across arms except for rash (14% vs 9%) and pruritus (12% vs 6%)
    • AEs leading to discontinuation of durva or placebo: 12% vs 6%

TRAEs leading to death: 1.8% vs. 0.5%

Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is at present the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial. In an exploratory analysis in 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone. Additionally, Imfinzi is approved in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial.

In addition to its indications in lung cancer, Imfinzi is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer in the US, EU, Japan and several other countries; in combination with Imjudo in unresectable hepatocellular carcinoma in the US, EU and Japan; and in previously treated patients with advanced bladder cancer in a small number of countries.

AstraZeneca has several ongoing registrational trials focused on testing Imfinzi in earlier stages of lung cancer, including in resectable NSCLC (ADJUVANT BR.31) and unresectable NSCLC (PACIFIC-2, 4, 5, 8 and 9), and in limited-stage SCLC (ADRIATIC).

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer and other solid tumours. 

Source: Press Release