Latest trends and developments in oncology from ASCO 2023
Seqens participated to this year’s annual meeting of the American Society of Clinical Oncology (ASCO), held in Chicago on June 2-6. This is the main event gathering every year the community of professionals on cancer treatments (oncologists, academic researchers, Pharma and Biotech) for the presentation and discussion of the last results of clinical trials, allowing to present new therapeutic options and to propose investigational treatments as the new standard of care for specific cancers.
This year’s ASCO gathered 43,000 professionals and 3,000 on ASCO-related events. Ronan Rocle, marketing manager for innovative technologies at SEQENS, gathered the latest developments and trends in this insightful article.
New treatments and therapeutic modalities allow to increase the share of patients cured from cancer
Cancer treatments continue to see a dramatic improvement as a diversity of novel therapeutic options enter the clinic or become widespread. During her plenary talk, Dr Monica M. Bertagnoli, National Cancer Institute director and recipient of the Allen Lichter visionary leader award, presented the levers to achieve the presidential « Cancer Moonshot » objective to reduce by half cancer mortality in the next 25 years and showed the tremendous and regular decrease of breast cancer mortality in the US since 1990 (while it was stable before). This steady decrease of cancer lethality since the 1990s is explained by the increase of therapeutic options. While surgery, chemotherapy and radiotherapy were initially the only therapeutic options, (once new) treatments modalities such as targeted small molecule inhibitors, monoclonal antibodies and antibody drug conjugates are now widely used, and additional modalities are emerging: bispecific antibodies, PROTACs, CAR-T, cancer vaccines (autologous dendritic cells or mRNA) and oncolytic viruses. This allows to provide oncologists with additional solutions to address the challenges of resistant tumors. Targeted therapies or combined treatments become progressively used at earlier stages of cancer to minimize relapse.
As an example, low grade glioma, a brain tumor, is currently treated by surgery then radiotherapy and chemotherapy. Dr Ingo Mellinghoff from the Memorial Sloan Kettering Cancer Center, presented the results of the INDIGO trial, a phase III clinical trial, which demonstrated that Vorasidenib, a selective small molecule inhibitor, was active against low grade glioma for patients exhibiting the IDH mutation, and could replace chemotherapy and radiotherapy as a first line of treatment after surgery.
Dr Yohann Loriot, from the Institut Gustave Roussy, presented the results of the THOR trial, a phase III clinical trial, which demonstrated the superiority of Erdafitinib, another selective small molecule inhibitor, compared to chemotherapy for the treatment of an advancer cancer, metastatic urothelial cancer, following an anti-PDL1 treatment. This trial supports Erdafitinib treatment to become the new standard of care for this indication.
Another phase III clinical study performed by the Institut Gustave Roussy was presented during the ASCO, the TALAPRO-2 trial. Pr Karim Fizazi presented that the combination of two small molecules, talazoparib, a PARP inhibitor, with enzalutamide, a nonsteroidal antiandrogen, could be used as a first line treatment for metastatic prostate cancers.
Mitigating the toxicities of cancer treatments
At the same time, these new or newer therapeutic modalities are associated with unique side effects and toxicities. We are still on the learning curve for these effects and protocols have to be established for the prediction or the early identification of adverse events.
For example, Antibody Drug Conjugates (ADCs) have known possible ophthalmologic toxicity. Dr Stella King presented these side effects and how to mitigate them. Dr Thomas Powles highlighted the improvements in the management of common side effects of ADCs through early detection of adverse events and perspectives on future developments to lower these toxicities.
Immuno-oncology treatments, for example using anti-PD1 or anti-PDL1 monoclonal antibodies, can cause autoimmune side effects, such as type 1 diabetes or cardiac toxicities. During the session « Traversing toxicities of Immuno-Oncologic agents », the prevention of these side effects was discussed, based on the understanding of underlying mechanisms. Dr Jennifer Mammen presented the mechanisms of the rare but significant diabetes phase I autoimmune adverse event. Bilal Sidiqui presented a model to explain cardiac toxicity and a treatment regimen to mitigate it.
There is an increasing evidence that the gut microbiome has an influence on immuno-oncology treatments efficacy and side effects. Dr Yinghong Wong and Dr Dikawar Davar described how microbiota transplants can lead to a reduction of immune adverse events following immune checkpoint inhibitors treatment.
Overall, the possibility to chose these new and targeted therapeutic options combined with a better prevention and management of these toxicities will enable to reduce deleterious side effects compared to chemotherapy and radiotherapy.
Personalized treatments based on tumor markers or patient’s tumor
Pan-tumoral approaches continue to emerge. The tumor treatment is based on molecular biomarkers, instead of initial tumor location.
As an example, during the session « New Drugs in oncology, incorporation into practice », Pr Vivek Subbiah talked about a pan-tumoral therapy for cancers associated with BRAF V600E mutation, a mutation which generates a constituvely activated BRAF mutant and promotes carcinogenesis, with a combination of a BRAF inhibitor and a MEK inhibitor.
Cancer vaccines based on the patient’s tumor are also a promising area with interesting developments.
Northwest Biotherapeutics presented the phase III results of DCVax-L, a cancer vaccine based on autologous dendritic cells incubated with the patient’s tumor lysate. DCVax-L was developed against glioblastoma, a brain cancer which has limited treatment options. Several patients in remission following this treatment were present in the audience.
A diversity of new generation treatments to come
The ASCO is also the opportunity to discover new developments on early therapeutic agents.
During the last few years, Pharma companies enriched their early stage oncology pipeline both in number of projects and diversity, which was highlighted by both Sanofi and Gilead.
During the presentation session entitled « Next generation Antibody Drug Conjugates: Past, Present and Future », Dr Erika Hamilton described how the new generation of ADCs will be able to overcome resistance observed for current treatments, through novel antibody structures, novel payloads and combination therapies.
In the poster presentation session « Developmental therapeutics – Molecularly targeted agents and tumor biology », Dr Wells A. Messerschmidt presented several promising small molecules under development (« Small molecules: ready for the big game ? »), such as Tinengotinib, a 2nd generation FGFR inhibitor with a unique binding mode allowing to overcome resistance to 1st generation inhibitors, or TTI-101, a small molecule STAT inhibitor.
For brain cancers or brain metastases, one of the challenges is to find drugs able to pass through the blood-brain barrier. During the session entitled « Breaking bad barriers: brain-penetrant small molecule inhibitors », Dr Ardama Shergill, Dr Varun Monga, Dr Qing Zhou and Dr Macarina Ines de la Fuente presented several small molecules in clinical phase which achieve this objective (Fore8394, PRT-811 and KL590586).
All these exciting new developments lead us to be very positive about the continuing downward trend in cancer mortality. Patient advocates and cancer survivors were also here to testify on the successes of new approaches. There are still a lot of challenges remaining, but the path forward comes from a deeper understanding of the diversity of cancers at a molecular level. As ASCO president Eric P. Winer stated during his inspirational speech, sharing his experience both as a prominent oncologist and as an haemophilia patient: « Science really matters ».
Ronan Rocle, Marketing Manager Innovative Technologies at SEQENS
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