In this latest instalment of his regular monthly column, Louis Gautier, Commissioning Editor of Future Oncology, exclusively shares his top 5 picks from the recent journal issues, which we have made freely available for you, Oncology Central members! Check out Louis’ highlights below:
Addressing resistance to immune checkpoint inhibitor therapy – an urgent unmet need
Immune checkpoint inhibitors (ICIs) targeted towards CTLA-4, PD-1 and PD-L1 have overhauled treatments for a range of cancer types, but patients’ responses to these therapies can be variable, unpredictable and short-lived. In their review, Siwen Hu-Lieskovan (Huntsman Cancer Institute, UT, USA) and colleagues aim to address this unmet need and discuss strategies for further research to overcome resistance to ICIs.
They begin by discussing known mechanisms of resistance and how tumor-intrinsic and patient-specific factors (including the gut microbiome) can affect these mechanisms. They also investigate pre-clinical and clinical trial data of various tumor types and how combination therapies have been developed with the aim of restoring antitumor immunity. As well as exploring the biology of treatment resistance, the authors stress that trial design and assessment criteria must continually be reviewed and updated to ensure they are appropriate for new therapies and can accurately identify patient populations that would benefit from ICI therapy.
PROs with durvalumab by PD-L1 expression and prior CRT-related variables in unresectable, stage III NSCLC
The PACIFIC Phase III trial (ClinicalTrials.gov: NCT02125461) was designed to assess the impact of durvalumab (Imfinzi®) on progression-free survival and overall survival in a broad population of unresectable, stage III NSCLC patients without disease progression after platinum-based chemotherapy. Durvalumab significantly improved survival outcomes, but further analyses of PD-L1 expression and treatment response led to the European Medicines Agency restricting use of the anti-PD-L1 therapy to patients with PD-L1 expression on tumor cells ≥ 1%.
In this Open Access research article, Marina Garassino et al. carried out exploratory, post-hoc analyses of patient-reported outcomes to better understand the impact of PD-L1 expression on the benefit/risk profile of durvalumab. Their results suggest that durvalumab had no detrimental effect on patient-reported outcomes irrespective of PD-L1 expression or variables related to prior chemotherapy.
PD-L1 testing by SP142 antibody in metastatic triple negative breast cancer: summary of an expert round-table discussion
Upregulation of PD-L1 is proven to be linked with improvements in survival for patients with locally advanced or metastatic triple-negative breast cancer being treated with ICIs. Clinical trial data from the Phase III IMpassion130 trial and the Phase III KEYNOTE-355 study, amongst others, demonstrate the value of PD-L1 testing in choosing patients who will benefit from ICI treatment.
In this article, Vicente Peg et al. present their summary of an expert round-table discussion on the various methods for assessing expression of PD-L1 in patients with advanced TNBC, where special focus was given to the VENTANA platform and the SP142 antibody. They answer key questions on the topic including: the reproducibility of SP142-determined PD-L1 expression; the recommended PD-L1 diagnostic algorithm and its relation to HER2/HR testing; and how the frequency of PD-L1 can differ depending on the sample evaluated. The round-table’s insight and the currently available knowledge has been discussed excellently, but further work is still required to make PD-L1 testing more consistently beneficial for patients.
Impact of biomarkers and primary tumour location on the mCRC first-line treatment landscape in five European countries
The landscape of treatment options for patients with metastatic colorectal cancer has improved considerably over recent years. This has largely been driven by the development of bevacizumab (Avastin®; a VEGF inhibitor), cetuximab (Erbitux®; an EGFR inhibitor) and a better understanding of prognostic and predictive biomarkers. In this research article, George Kafatos et al. set out to collect real-world data on first line treatment choices for metastatic colorectal cancer patients treated in 2018 across five European countries (Italy, Germany, France, Spain and the UK).
The authors found that there were large differences in treatment patterns according to biomarker status and primary tumor location, with RAS wild-type patients mainly being treated with anti-EGFR therapy plus chemotherapy and RAS-mutant patients most commonly treated with anti-VEGF therapy plus chemotherapy. However, they also note some differences in treatment practices between countries and highlight the need for further research and the development of more stringent treatment guidelines for physicians.
How we treat Merkel cell carcinoma: within and beyond current guidelines
Articles discussing treatment practices of a specific group are a new development for Future Oncology and this manuscript by Song Park et al. is the first from the University of Washington (WA, USA) describing their experience with Merkel cell carcinoma. This rare and aggressive form of cancer has benefited from a rapid improvement in knowledge across different specialties; however, along with the relatively low incidence, this has created several controversies around management decisions.
In this article, the authors discuss the current treatment guidelines and available review articles on the disease, which they suggest are only broadly clinically relevant and can leave grey areas for oncologists when considering more personalized treatment options. They highlight the value of a multi-disciplinary strategy to account for these grey areas and provide more context to support oncologists in making treatment decisions based on the most current data and their own experiences. The group also cover some pivotal clinical trials that aid in extrapolation of treatment indications, some representative case studies and the role of surveillance.