Attending the American Society of Clinical Oncology (ASCO) annual meeting this year was another great opportunity to learn more about recent treatment advances in multiple tumor types, some of which will be practice-changing for physicians. With so many interesting research breakthroughs presented, it is difficult to select what to highlight, so I will focus on what will impact treatment with an emphasis on the role of biomarkers and the future of the immune-oncology field.

The MONALEESA-7 trial in premenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer reported a clinically and statistically significant longer overall survival rate in patients treated with a CDK4/6 inhibitor (ribociclib) +/- endocrine therapy than with endocrine therapy alone [median not reached vs. 40.9 months, HR, 0.712 [95% CI, 0.54-0.95]; p=0.00973). This is the first time that a CDK4/6 inhibitor or any targeted therapy in combination with endocrine therapy has demonstrated a significantly longer overall survival rate versus endocrine therapy alone.

Another study that reported an overall survival benefit was the ENZAMET trial, a phase III study of enzalutamide along with standard of care compared with other non-steroidal anti-androgens and standard of care in patients with metastatic hormone-sensitive prostate cancer. Enzalutamide is a potent direct inhibitor of the androgen receptor with established benefit in castration-resistant prostate cancer. At 36 months, 80% of patients in the enzalutamide group remained alive, compared with 72% in the NSAA group (HR 0.67, 95% CI [0.52, 0.86]; p=0.002).  While the overall survival difference was more apparent in patients who did not receive docetaxel, it is considered a remarkable result. The early use of enzalutamide could help patients avoid chemotherapy and steroids for many years, thereby improving their quality of life.

The phase III POLO trial presented at the plenary session reported that maintenance therapy with olaparib prolonged progression-free survival in patients with metastatic pancreatic cancer with a germline BRCA mutation. The median progression-free survival was 7.4 months in the olaparib arm vs. 3.8 months in the placebo arm. Olaparib was administered following first-line therapy with platinum-based chemotherapy. This is the first trial to validate a targeted treatment in a biomarker-selected population of pancreatic cancer patients and highlights the importance of testing for the germline BRCA mutation in this setting.

The role of biomarkers in predicting survival was analyzed in the JAVELIN Renal 101 phase III study and provided an important contribution to understanding the individual differences in patients who may best respond to avelumab and axitinib versus sunitinib monotherapy as first-line therapy for patients with advanced renal cell carcinoma. It gives oncologists a potential new strategy for offering a personalized treatment option to this high-risk population.

JAVELIN Renal 101 found longer PFS and better overall response rates from combination avelumab and axitinib than sunitinib monotherapy administered as a first-line treatment for patients with advanced RCC. Biomarkers of interest included PD-L1 expression, CD8 expression, gene expression profiling, and various other mutations and polymorphisms.

Results showed no differences in survival among patients who were PD-L1 positive or negative and received combination avelumab and axitinib (p = 0.4734). However, those who received sunitinib and were PD-L1 positive had significantly shorter PFS than patients who were PD-L1 negative (p = 0.0037). Furthermore, patients with a greater number of CD8-expressing cells (i.e., higher than median levels) demonstrated significantly longer PFS than patients with fewer CD8-expressing cells in the combination arm (p = 0.0343) but no difference in the monotherapy arm (p = 0.0815).

Gene expression profiling revealed that high expression of a 306-gene signature, derived from 4,622 genes, was significantly correlated with longer PFS with combination therapy but not monotherapy.  A smaller subset comprising a 26-gene signature accounted for the strongest association between gene expression and PFS with combination treatment; however, it had no relationship with PFS in monotherapy. The 26-gene signature included T-cell receptor signaling; T-cell activation, proliferation, and differentiation; NK cell-mediated toxicity; chemokines; and other immune response genes.

The next checkpoint target gaining considerable interest is CD47. 5F9, from Forty Seven, targets CD47, a macrophage immune checkpoint that normally tells the immune system not to attack cancer cells. By blocking CD47, 5F9 induces tumor phagocytosis and eliminates leukemia stem cells in AML models. Once CD47’s signal is removed, azacytidine introduces a new signal to the cancer cells that does the opposite of CD47, telling the immune system to attack cancer cells and enhancing phagocytosis.

A phase IB trial tested 5F9 on AML and MDS patients, also including AZA for untreated, chemo-ineligible AML and high-risk MDS patients. Eight of the 25 patients judged to be efficacy evaluable experienced complete remission (with or without complete hematologic recovery) while 10% of all patients had a positive response to 5F9 individually without the addition of AZA.

It is always exciting to attend ASCO and see the progress being made in oncology research and the passion everyone in this field brings to their work. I look forward to hearing about new breakthroughs in 2020.