When I went to my first American Society for Clinical Oncology Annual Congress, in 2002, targeted therapies were still relatively new, and the promise of anti-angiogenic therapies had yet to be realised. Eighteen years later, the cancer treatment landscape has changed dramatically. I’ve been lucky to have had a front-row seat to see so many exciting new therapies transform cancer treatment and improve patient’s lives. Although this year’s seat was at home due to COVID19, I’d like to share my perspective on some of the exciting developments I learned about during Virtual ASCO 2020.
Several potentially practice-changing clinical trials were presented.
Together, a number of studies have advanced our approaches to managing patients, providing them with significantly better treatment options. Studies that were particularly noteworthy included:
1. JAVELIN Bladder 100, which reported an improvement in overall survival in patients with advanced urothelial carcinoma with maintenance avelumab + best supportive care (BSC) compared with BSC alone after first-line chemotherapy, which was even more pronounced in the PD-L1+ population;
2. KEYNOTE-177, which showed a doubling of median progression-free survival compared with chemotherapy in patients with microsatellite instability-high or mismatch repair-deficient (MSI-H/MMRd) mCRC; and
3. ADAURA, which showed significantly improved disease-free survival as an adjuvant therapy in patients with stage 1B-IIIA EGFRm NSCLC after complete tumour resection and adjuvant chemotherapy where indicated.
An array of approaches aimed at harnessing the immune system to fight cancer are now being investigated.
The idea that we could harness the power of one’s own immune system to fight cancer has long been an attractive concept, and the success of immune checkpoint inhibitors, bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies have ushered in a new era of immuno-oncology. New approaches currently being investigated include more highly engineered therapeutic cancer vaccines, and a number of engineered T cells which can recognise an increasing variety of tumour antigens. These can be used alone or in combination with checkpoint inhibitors to enhance their therapeutic effect. Additional approaches to engineering antibodies include the use of mutations to encourage hexamer formation and enhance the immune response, and novel approaches to developing antibody drug conjugates to deliver cytotoxic payloads to cancer cells.
Could the future of precision medicine be tumour agnostic and biomarker-driven?
Currently, most cancer is treated according to tumour type. However, as we learn more about the heterogeneity of different tumours, and their different oncogenic driver mutations, it has become attractive to consider that targeted therapies could be used in patients whose tumours have specific mutational profiles, irrespective of the tumour of origin. Proof of concept for this approach has already led to the approval of larotrectinib in solid tumours with NTRK fusions and of pembrolizumab in MSI-H/MMRd solid tumours. Biomarker-selected treatments are currently being investigated in patients with rare tumours for which there are no evidence-based treatments and for patients with advanced cancers without remaining treatment options. At ASCO this year, results from the TAPUR study show encouraging data supporting a role for olaparib in the treatment of patients with advanced prostate and pancreatic cancers who harbour BCRA1/2 mutations. The ARROW study, which is ongoing, showed encouraging results in patients with RET fusion-positive solid tumours. In addition, the NAVIGATOR study assessed using next-generation sequencing to identify actionable mutations in patients with rare tumours.
Our approach to treating cancer continues to evolve. We may soon see the day where individual molecular characteristics routinely drive our approach to managing most tumours and harnessing the immune system to fight cancer will be standard. Until that time, it is heartening to see the extraordinary compassion and creativity with which clinicians and researchers approach the fight against cancer.
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