ASCO 2020: Key abstracts and practice-changing findings

While this year’s virtual ASCO meeting may have felt quite different from the traditional hustle and bustle of Chicago’s McCormick Place, the global oncology community remains focused on “uniting and conquering” to advance oncology care, as this year’s theme suggested. Many abstracts were presented across multiple disease states, bringing forth promising new treatment options and important implications for oncology practices, some of which quickly resulted in FDA approvals for new indications.

The clinical experts of Cardinal Health Specialty Solutions have sorted through the findings of significant studies across multiple disease states as well as research on the latest advances in CAR-T therapy from this year’s meeting to summarize the research that is likely to have an impact on clinical practice.  Here are some of the highlights from this year’s meeting.

The development of “off-the-shelf” or universal CAR-T therapies – therapies that would replace autologous chimeric antigen receptor (CAR) T cells with allogenic CAR-T cells – would have many potential advantages. Not only would these therapies be more efficient to produce, but they would potentially be a safer for patients and have lower levels of toxicity. Allogeneic ("off-the-shelf") CAR-T can potentially shorten waiting times for these patients with aggressive lymphomas. However, as with allogeneic stem cell transplantation, deep levels of lymphodepletion are needed to combat the CD52 protein.

Results from the phase 1 ALPHA trial presented at ASCO address both of these issues by targeting the tumor with ALLO-501 (an allogeneic anti-CD19 CAR-T) and targeting CD52 with ALLO-647 (an anti-CD52 monoclonal antibody). The abstract reported preliminary data on 9 patients who received ALLO-501, with 3 complete and 4 partial responses. No dose-limiting toxicities (DLTs) or graft-vs-host disease (GvHD) were observed. Two patients developed cytokine release syndrome and 1 patient developed Grade 1 neurotoxicity that resolved without treatment. Although this study only included a small number of patients and a short follow-up period, the results presented generated significant excitement and a glimpse of what may be possible for off-the-shelf CAR-T therapies in the future.

Recent research in colorectal cancer (CRC) has explored enhancing outcomes with immune checkpoint inhibitors in microsatellite instability-high (MSI-H) disease. Exciting findings from the phase 3 KEYNOTE-177 study presented at ASCO demonstrated significant and clinically meaningful improvement in progression free survival (PFS).

The study assessed the outcomes of first-line pembrolizumab (Keytruda®) compared to the standard of care, chemotherapy ± bevacizumab or cetuximab, for patients with MSI-H or deficient mismatch repair (dMMR) metastatic CRC. The results showed that frontline pembrolizumab improved doubled PFS from 8.2 months to 16.5 months, compared with the standard chemotherapy regimen studied and also demonstrated lower rates of grade 3-5 treatment-related adverse events.

Just one month after these promising results were presented, the FDA approved pembrolizumab as a single-agent, first-line treatment for patients with unresectable or metastatic CRC and certain key genetic mutations.

Remarkable results were reported in the ADAURA study of early-stage non-small cell lung cancer (NSCLC) patients, showing promising progress in the disease state that affects the vast majority of lung cancer patients.

The three-year ADAURA study evaluated the long-term effects of osimertinib (Tagrisso®), which is currently an established front-line treatment option for advanced NSCLC patients with the EGFR mutation, as an adjuvant therapy. The phase 3 trial looked at survival and recurrence of cancer in post-surgical, early-stage EGFR mutated NSCLC compared to a placebo. The results showed an 83 percent reduction in the risk of disease recurrence or death across all subgroups, with 89 percent of patients remaining alive and disease-free after two years. Based on these highly positive results, a future approval for Osimertinib in this disease state is likely.

Over the past several years, the approvals of five PD-1/PD-L1 inhibitors – nivolumab (Opdivo®), pembrolizumab (Keytruda®), atezolizumab (Tecentriq®), avelumab (Bavencio®), and durvalumab (Infinzi®) – have paved the way for exploration of these immunotherapies in the treatment of advanced urothelial cancer.

At the virtual ASCO session, results of the JAVELIN Bladder 100 trial were among the most significant findings for urothelial cancer in several decades, demonstrating the potential for avelumab to become a new standard of care. The phase 3 study evaluated 700 patients with stable or responding disease on first-line chemotherapy to either avelumab as a first-line maintenance immunotherapy or observation. Patients receiving avelumab had a significantly longer median survival rate (21 months) than patients who received best supportive care (14 months). Efficacy benefits were seen across all subgroups and the safety profile of avelumab was consistent with previous studies of monotherapy. Based on these positive findings, the FDA recently approved avelumab for first-line maintenance treatment of locally advanced or metastatic urothelial carcinoma, making this therapy the first medicine in the PD-1/PD-L1 class in this disease state.

For additional summaries compiled by Cardinal Health Specialty Solutions clinical experts and their colleagues, please visit our ASCO summaries landing page, featuring abstracts in myeloma, prostate cancer, leukemia, lymphoma and more.