AstraZeneca presented data from two phase 3 trials at the annual American Society for Clinical Oncology (ASCO) meeting. The first data presentation was for the PACIFIC trial, which evaluated Imfinzi (durvalumab) in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who had not progressed following concurrent chemoradiation therapy (CRT). Data demonstrated a sustained, clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit at five years. The second presentation was for the OlympiA trial, showed Lynparza (olaparib) demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS) versus placebo in the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.
The PACIFIC trial was a randomized, double-blinded, placebo-controlled trial of Imfinzi as treatment in ‘all-comer’ patients (regardless of PD-L1 status) with unresectable, Stage III NSCLC whose disease had not progressed following concurrent platinum-based CRT. The trial was conducted at 235 centers across 26 countries involving 713 patients. The primary endpoints of the trial were PFS and OS, and secondary endpoints included landmark PFS and OS, objective response rate and duration of response.
Results from the updated post-hoc analyses showed an estimated five-year OS rate of 42.9% for patients treated with Imfinzi versus 33.4% for those on placebo after CRT. Median OS was 47.5 months for Imfinzi versus 29.1 for placebo. Following a maximum treatment course of one year, an estimated 33.1% of patients treated with Imfinzi had not progressed five years after enrolment versus 19% for placebo.
OlympiA was a double-blind, placebo-controlled trial testing the efficacy and safety of Lynparza tablets versus placebo as adjuvant treatment in patients with gBRCAm, high-risk, HER2-negative early breast cancer, who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. The primary endpoint of the trial is iDFS defined as time from randomization to date of first loco-regional or distant recurrence, new cancer or death from any cause.
In the overall trial population of patients who had completed local treatment and standard neoadjuvant or adjuvant chemotherapy, results showed Lynparza reduced the risk of invasive breast cancer recurrences, second cancers or death by 42%. At three years, 85.9% of patients treated with Lynparza remained alive and free of invasive breast cancer and second cancers versus 77.1% on placebo.
Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.
About Stage III NSCLC
In 2020, an estimated 2.2 million people were diagnosed with lung cancer worldwide. Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC. Stage III NSCLC represents approximately one quarter of NSCLC incidence. Stage III (locally advanced) NSCLC is divided into three subcategories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally. In contrast to Stage IV, when cancer has spread (metastasized), the majority of Stage III patients are currently treated with curative intent.
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumor types with defects and dependencies in the DDR pathway.
Early breast cancer
Breast cancer is the most common cancer among women worldwide and an estimated 70% of all breast cancer is diagnosed at an early stage.
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including Lynparza.