These results will be presented today in an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract #LBA5506).
The combination of LYNPARZA, IMFINZI, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 37% versus chemotherapy and bevacizumab (hazard ratio (HR) 0.63; 95% CI 0.52-0.76; p IMFINZI, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 51% versus chemotherapy and bevacizumab alone (HR 0.49; 95% CI 0.34-0.69; p Professor Philipp Harter, Director, Department of Gynaecology and Gynaecologic Oncology, Evangelische Kliniken Essen-Mitte, Germany, and principal investigator for the trial, said: “The primary aim of first-line treatment of patients with advanced ovarian cancer is long-term control over the disease, but still too many patients progress quickly and face poor clinical outcomes today. Data from the DUO-O trial interim progression-free survival analysis provide evidence for further improvement with olaparib and durvalumab combination versus chemotherapy and bevacizumab alone in patients without tumor BRCA mutations.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These results are an important milestone in our ongoing journey to address unmet need in ovarian cancer. The DUO-O trial demonstrates the potential of combining PARP inhibition with immunotherapy and we look forward to seeing more mature data and key secondary endpoints results.” At a pre-planned exploratory analysis of the HRD-negative subgroup of patients, LYNPARZA, IMFINZI, chemotherapy and bevacizumab reduced the relative risk of disease progression or death by 32% versus chemotherapy and bevacizumab (HR 0.68; 95% CI 0.54-0.86). Median PFS was 20.9 months versus 17.4. At the time of this interim analysis, an additional arm evaluating the combination of IMFINZI, chemotherapy and bevacizumab demonstrated a numerical improvement in PFS which was not statistically significant (HR 0.87; 95% CI 0.73-1.04; p=0.13). At the time of this planned interim analysis, the overall survival (OS) and other secondary endpoints were immature. OS will be formally assessed at a subsequent analysis.
Summary of results: DUO-O
*Results based on the stratified model
**Results based on the unstratified model: HR 0.51 (95% CI 0.36-0.72)
The safety and tolerability of these combinations was broadly consistent with that observed in prior clinical trials and the known profiles of the individual medicines.
The most common adverse events (AEs) (greater than or equal to 20% of patients) for the combination of LYNPARZA, IMFINZI, chemotherapy and bevacizumab were nausea (57%), anemia (55%), neutropenia (51%), fatigue/asthenia (49%), arthralgia (34%), constipation (30%), diarrhea (30%), thrombocytopenia (28%), hypertension (26%), vomiting (26%), leukopenia (24%), headache (22%), abdominal pain (21%) and hypothyroidism (20%). Grade 3 or higher AEs were neutropenia (31%), anemia (24%), leukopenia (8%), hypertension (7%) and thrombocytopenia (6%). Approximately 65% of patients treated with the combination of LYNPARZA, IMFINZI, chemotherapy and bevacizumab who experienced AEs during chemotherapy and throughout the maintenance phase remained on treatment at the time of data cut-off, compared to 80% of patients in the control arm (chemotherapy plus bevacizumab). Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
Please refer to the full Prescribing Information for important dosage modification and management information specific to adverse reactions.
IMPORTANT PRODUCT INFORMATION
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune-mediated dermatologic reactions, immune-mediated pancreatitis, and solid organ transplant rejection. IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treat with a PD-1/PD-L1 blocking antibody. Advise women not to become pregnant or breastfeed during treatment with IMFINZI and IMJUDO and for 3 months after the last dose. The most frequent serious adverse reactions reported in at least 2% of patients with unresectable, Stage III NSCLC were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). The most frequent serious adverse reactions reported in at least 2% of patients with metastatic NSCLC were pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). The most frequent serious adverse reactions reported in at least 1% of patients with ES-SCLC were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%) and COPD (1.1%). The most frequent serious adverse reactions reported in at least 2% of patients with locally advanced or metastatic BTC were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%), and acute kidney injury (2.4%). Serious adverse reactions in >1% of patients with uHCC included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Most common adverse reactions (≥20% of patients with unresectable, Stage III NSCLC) were cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash. The most common adverse reactions (≥20% of patients with metastatic NSCLC) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%). Most common adverse reactions (≥20% of patients with ES-SCLC) were nausea, fatigue/asthenia, alopecia. The most common adverse reactions (≥20% of adult patients with locally advanced or metastatic BTC) were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia. The most common adverse reactions (occurring in ≥20% of patients with uHCC) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain. The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients. Please refer to the full Prescribing Information for important dosage modification and management information specific to adverse reactions.
Ovarian cancer is one of the most common gynecologic cancers and is the eighth most common cancer in women worldwide with more than 314,000 new patients diagnosed in 2020 and over 207,000 deaths. This number is expected to rise by almost 42% by 2040 to over 445,000 newly diagnosed patients and 314,000 deaths.1,2,3 DUO-O is a Phase III randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of IMFINZI in combination with platinum-based chemotherapy and bevacizumab followed by maintenance treatment with IMFINZI and bevacizumab with or without LYNPARZA in newly diagnosed patients with advanced ovarian cancer without tumor BRCA mutations. Patients were randomized 1:1:1 to: Arm 1 (control), induction therapy with platinum-based chemotherapy in combination with bevacizumab and placebo followed by maintenance treatment with bevacizumab plus placebo; Arm 2, induction therapy with platinum-based chemotherapy in combination with bevacizumab and IMFINZI followed by maintenance IMFINZI and bevacizumab plus placebo; or Arm 3, induction therapy with platinum-based chemotherapy in combination with bevacizumab and IMFINZI followed by maintenance IMFINZI and bevacizumab plus LYNPARZA. In all arms, platinum-based chemotherapy was administered every 3 weeks (q3w) for up to 6 cycles, bevacizumab was administered q3w for up to 15 months, IMFINZI or placebo was administered q3w for up to 24 months, and LYNPARZA or placebo was administered twice daily for up to 24 months. The primary endpoint of the trial is progression-free survival (PFS) as assessed by investigator for Arm 3 compared to Arm 1 (control) in the overall trial population which included patients without tumor BRCA mutations and in the subset of these patients with homologous recombination deficiency (HRD)-positive disease. Key secondary endpoints include PFS as assessed by investigator in Arm 2 compared to control, as well as comparisons for overall survival (OS). DUO-O enrolled over 1200 patients across all treatment arms at 179 study locations. For more information about the trial, visit ClinicalTrials.gov. 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 tumor’s immune-evading tactics and releasing the inhibition of immune responses. LYNPARZA® (olaparib) is a first-in-class PARP inhibitorPARP 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 those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents [NHAs]). 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, which is being jointly developed and commercialized by AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada, has been used to treat over 75,000 patients worldwide. The companies develop LYNPARZA in combination with their respective PD-L1 and PD-1 medicines independently. LYNPARZA is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells. AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. By harnessing the power of six scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics and Cell Therapies – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death. AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.