Title:Durvalumab in Oncology: Pioneering Advances through Recent Clinical Trials and Expanding Therapeutic Horizons
Volume: 11
Author(s): Afzal Hussain*Ashfaq Hussain
Affiliation:
- Department of Bioinformatics, Maulana Azad National Institute of Technology, Bhopal, 462003, India
Keywords:
Durvalumab, immunotherapy, non-small cell lung cancer (NSCLC), tumor microenvironment, clinical trials, chemotherapy.
Abstract: Durvalumab, the programmed death-ligand 1 (PD-L1) targeting monoclonal antibody,
has revolutionized the treatment of numerous cancers, such as Non-Small Cell Lung Cancer
(NSCLC). Despite producing remarkable clinical advantages, immune-related toxicities, i.e.,
pneumonitis and colitis, are being closely monitored and must be treated on an individual basis.
The safety profile, including immune-related toxicities, must be carefully considered. The role of
Durvalumab as a consolidative treatment for unresectable stage III NSCLC, as demonstrated in
the PACIFIC trial, marked a significant milestone in the adoption of immunotherapy. However,
recent findings suggest that its benefit varies among patient subgroups, highlighting the need for
more precise biomarkers beyond PD-L1 expression. Ongoing trials, such as PACIFIC-9 and
AEGEAN, are investigating durvalumab in different settings and combination therapies with an
aim to overcome resistance mechanisms. The PACIFIC-9 is an example where durvalumab is
being combined with the CD73-blocking anti-CD73 antibody oleclumab and the CD94/NKG2Ablocking
monalizumab in unresectable stage III NSCLC patients who maintain a stable response
through chemoradiotherapy. Early findings are encouraging, but phase III efficacy data remain
awaited. Heterogeneity in treatment response between tumor types, including bladder carcinoma,
head and neck cancers, and cholangiocarcinoma, is one reason why it is worth aiming for tumorintrinsic
and microenvironmental determinants of responsiveness to immunotherapy. Durvalumab
is of landmark significance in a range of malignancies but needs further efforts in the characterization
of resistance mechanisms, the optimization of combination strategies, and the development
of predictive models for the guidance of personalised therapeutic regimens.
