Recapping Days 3 & 4 of the 2021 ESMO Congress

The European Society for Medical Oncology (ESMO) 2021 Congress continued with its wide selection of educational, multidisciplinary sessions exploring a variety of topics and highlighting clinical trial data and emerging research in the field of oncology.

Below are some of the highlights from the third and fourth days of ESMO’s 2021 Congress.

Assessing the Role of HRD Testing in Clinical Practice

As the world of molecular profiling continues to grow, should we be incorporating homologous recombination repair deficiency testing in clinical practice? Day 3 of the ESMO Congress featured the “Should we test our patients in clinical practice with HRD? How and when?” session, which was led by Florence Joly Lobbedez from Caen, France.

Dr. Isabelle Ray-Coquard, a researcher from Lyon, France, argued in favor of HRD testing for ovarian cancers, and said that all patients with newly deigned ovarian carcinoma should have somatic or germline testing to establish BRCA mutation and HRD status.

Dr. Ray-Coquard explored HRD from several perspectives: as a factor to identify a particular population, as a prognostic factor, and as a predictive factor.

From the patient population perspective, high-grade, serious ovarian cancers are split into two classes, and each class can be identified by the patient’s HRD status. From a prognostic perspective, HRD testing was used as a prognostic factor for PFS in first-line clinical trials PRIMA and Veila and helped estimate chance of recovery and risk of recurrence. From a predictive perspective, HRD testing in patients has increased the response rate in this patient population.

Dr. Ray-Coquard noted that HRD testing has demonstrated clinical utility. Clinicians with knowledge of their patient’s HRD profile can facilitate switching between biologics or developing more suitable treatment options for their patient.

She concluded by saying that determining HRD status may be important for stratification in clinician trials for novel DDR agents and IO combos in frontline and recurrent settings.

Following Dr. Ray-Conquard, Dr. Antonio Gonzalez Martin from Madrid, Spain argued that HRD testing should be used preferably with BRCA testing prior to the end of first-line chemotherapy, but also that there is still a need for new, alternative validated HRD tests.

Dr. Martin began by noting that there’s only one type of HRD testing that has been validated in frontline trials. And in the PRIMA and PAOLA-1 trials, he said that we’ve seen benefit in testing for HRD and BRCA mutations simultaneously and prior to the end of first-line treatment.

But according to, clinical trial data, our current HRD testing is not enough, and we need new, alternative, validated HRD tests. Currently, HRD tests are no equivalent and are not interchangeable. And due to genomic instability, HRD testing results may not always be accurate.

Dr. Martin concluded that there’s a need for the development of new, validated HRD tests in the context of absence of access to GIS, and patients should at least be tested for the BRCA gene mutation.

After both Drs. Ray-Coquard and Dienstmann presented their arguments, Dr. Martin concluded the session by polling the attending oncologists for their perspectives on the following three statements:

• All the newly diagnosed high-grade ovarian carcinoma patients should have molecular testing (i.e. HRD testing) even without genetic predisposition, during initial management
• Molecular testing (i.e. HRD testing) should include somatic/germline BRCA gene mutation and tumoral genomic instability score
• When you ask for a molecular testing, turmoil instability score must be explored after BRCA status

While most responded ‘yes’ to the first and second questions, the final question drew mixed results, with more research needed to better understand HRD testing and molecular profiling.

Drug Development: How Can Academia & Industry Work Together?

While academia and industry do currently work together, these two parties often have different agendas. And considering that there are unmet needs for new therapies in oncology, day 4 of the ESMO Congress featured the session, “Drug Development: How Can Academia & Industry Work Together?” Led by Dr. Jean-Charles Soria from Bethesda, this session reviewed why and how academia and industry can better collaborate.

Beginning with some background on this issue, Dr. Soria noted that the number of cases and deaths are increasing because cancer is now affecting many new regions in the world. In fact, the global cancer burden is expected to increase by 47 percent between 2020 and 2040. Additionally, there’s a need to improve efficacy in pharma R&D investment since R&D expenditure is increasing over time.

Dr. Soria then shared the different advantages of academia and industry from his own vantage point. He argued that academia has the capability to identify new targets, concepts, and biomarkers and to conduct real-time transactional science while industry is the best at developing medicines for a given therapeutic target and assessing the pharmacology of the product.

Based on these strengths, Dr. Soria argued that there’s a shared goal of these two parties to achieve the optimal development of new innovative therapies that provide meaningful benefits to patients. However, there are several challenges that can keep academia and industry from achieving this primary goal, such as financial and IP incentives.

To demonstrate how academia and industry can work better together, Dr. Soria shared the following examples of effective collaboration:

• Academia can develop integrated research programs that characterize industry assets.
• Academia can help industry by generating data that is meant for drug development.
• Industry can help create flexible clinical trial designs that leverage academia strengths.

Through these collaborative efforts, research and trials can help uncover new patient populations who will be eligible for new drugs and approvals, drug combinations, and toxicity.

To wrap up, Dr. Soria argued that key stakeholders need to realize that huge efficiencies can come from an optimized collaboration between academic and industry and that at the root of these two parties is a shared goal: to develop new therapies that can help patients.

Stay at the Bench Or Move to the Bedside: What Is the Role for Neoadjuvant Therapy in Melanoma Today?

There have been major breakthroughs in stage II adjuvant therapy, leading many oncologists to wonder how to best treat patients to avoid toxicity and needless treatment…and if neoadjuvant therapy could be the answer. That’s why Dr. Omid Hami from Los Angeles led the “Stay at the Bench Or Move to the Bedside: What Is the Role for Neoadjuvant Therapy in Melanoma Today?” session that sought to address this controversial issue on day 4 of the ESMO Congress.

Taking the stage in support of the use of neoadjuvant therapy was Dr. Paolo Ascierto from Naples, Italy. He noted that there’s a high proportion of patients who can’t benefit from adjuvant therapy, which has led to an increased interest in neoadjuvant therapy in the past several years. That stage II research across a variety of cancer types has found that neoadjuvant therapy is associated with clinical benefits.

For instance, the short duration of treatment has been shown to improve patients’ quality of life, and the discontinuation of treatment due to adverse events is lower among patients receiving neoadjuvant therapy compared to adjuvant therapy.

While he admitted that some—like his own opponent in this controversy session—would like to see data from randomized studies, he argued that some stage III trials are already in the works, and based on the research thus far, Dr. Ascierto supports the use of neoadjuvant therapy for patients with palpable and resectable disease or resectable oligometastatic disease.

Dr. Rienhard Dummer from Zurich, Switzerland was up next to share this viewpoint: that while there are some advantages of neoadjuvant therapies, Dr. Dummer believes that neoadjuvant therapy is appropriate for clinical trial and biomarker work—not in the clinic.

To support this stance, he listed some of the advantages of adjuvant therapy, including:

• Exact tumor staging by histology
• No acute complications of surgery
• No impact of adverse events on treatment or surgery

Dr. Dummer then noted that a limited number of melanoma patients participated in the neoadjuvant therapy study while 3,293 patients participated in adjuvant therapy trials. Additionally, adjuvant therapy is not only approved and reimbursed in most countries, but it also has documented long-term impacts on relapse-free survival and overall survival.

Since the long-term outcome of neoadjuvant therapy is not yet available, Dr. Dummer concluded that neoadjuvant trials are appropriate for unresectable stage III melanoma in the context of clinical trials as translational research tools but not the clinic.

To bring all of this together, Dr. Hami polled the attending oncologists and received the following results:

• Question (with the majority answer being "no"): Is neoadjuvant therapy ready for usage in general oncology practices?

• Question (with the majority answer being "no"): Is neoadjuvant therapy associated with better outcomes, stage for stage, than adjuvant therapy?

• Question (with the majority answer being "yes"): Can neoadjuvant therapy help fashion appropriate predictive and prognostic biomarkers for adjuvant and metastatic therapy/trials?

• Question (with the majority answer being "no"): Are neoadjuvant therapy trials appropriate for unresectable stage 3 melanoma?

None of the above questions received a unanimous response, however. This shows that the use of neoadjuvant therapy in melanoma still remains a controversial issue that deserves much more investigation.