On April 23, 2020, the AACR held a preview press conference in advance of its first-ever Virtual Annual Meeting I taking place April 27 - 28, 2020, necessitated by the Covid-19 pandemic.
“We are living in unprecedented times and certainly not what we imagined when we were planning this meeting one year ago. The virtual meeting will permit rapid sharing of new results and cutting-edge information,” said AACR President Elaine R. Mardis, PhD.
AACR President-Elect Antoni Ribas, MD, PhD, focused on clinical trials to be presented at eight Plenary Sessions during the virtual meeting, and added that there would be a wide array of other presentations featured over the two-days, including mini-symposia, posters, award-winning lectures, and a special session on coronavirus and cancer.
A second virtual meeting is planned for June 22 - 24, 2020—the AACR Virtual Annual Meeting II.
Opening Plenary Session
The I-SPY 2 trial compared the combination of the checkpoint Inhibitor durvalumab in combination with the PARP inhibitor olaparib and paclitaxel versus chemotherapy alone in patients with high-risk HER2-negative stage II/III breast cancer (Abstract CT011).
Patients who received the combination therapy had significantly improved pathological compete response (a surrogate endpoint) over the chemotherapy alone treatment arm, including those with triple-negative breast cancer, which is considered a hard-to-treat subtype.
“This study showed that triple therapy is better than chemotherapy in shrinking breast cancer,” said Dr. Ribas.
Abstract CT012 presents results of the IMspire 150 trial in previously untreated patients with BRAFV600-positive advanced melanoma. The addition of the checkpoint inhibitor atezolizumab to cobimetinib and vemurafenib led to more durable responses, improved progression-free survival, and increased duration of response compared with those treated with cobimetinib plus vemurafenib plus placebo.
“The IMspire 150 study is practice-changing,” noted Dr. Ribas.
Commenting on the first two abstracts where immunotherapy is combined with chemotherapy and/or targeted drugs, Dr. Ribas said, “The toxicities and the economic implications are important. The toxicities [of these regimens] will be presented at the virtual meeting, but the economic implications will require additional analysis and will be forthcoming.”
A separate study in BRAF-mutated melanoma (Abstract CT013) showed that continuous dosing of dabrafenib and trametinib nearly doubled progression-free survival (from 5.5 months to 9 months) compared with intermittent dosing but did not improve survival. The study suggests that continuous dosing may delay resistance to these two agents.
IMbassador250 was a Phase 3 trial (Abstract CT014) that compared atezolizumab plus enzalutamide versus enzalutamide alone in patients with metastatic prostate cancer. Despite hopes of improving outcomes with the checkpoint inhibitor, no survival benefit was observed compared with enzalutamide alone.
Early Detection and ctDNA
Dr. Ribas singled out two abstracts (CT021 and CT022) from a Plenary Session on early detection and ctDNA screening that used two different liquid biopsy tests—a cell-free DNA multicancer early detection test in individuals with suspicion of cancer, and the DETECT test in 10,000 women with no history of cancer. Both studies found that this cancer screening modality was able to confirm the presence of cancer as well as the site of origin of the cancer before many of these cancers would be diagnosable otherwise.
“These studies in thousands of patients provide support for using these tests. This session will be remembered as when we saw the big data to support use of these tests. We need regulatory approval but I don’t think it will take that long to enter practice,” said Dr. Ribas.
Dr. Mardis commented by pointing out that both researchers used these tests in different but innovative ways to pick up the site of cancer. “This minimizes follow-up testing that occurs clinically. It would be a good problem to have if we picked up cancers too early to be otherwise diagnosed that required no treatment. I don’t think that will happen because the focus is on cancers detected late where the need is most pressing for cancer detection.”
A third presentation at the same session on ctDNA described a liquid biopsy that can detect minimal residual disease (MRD) following surgery for non-small-cell lung cancer well ahead of clinical relapse, in addition to defining the clonality of relapsing disease (Abstract CT023).
Adoptive Cell Transfer Therapy
A Plenary Session on adoptive cell transfer therapy will focus on next-generation CAR-T products. Abstract CT052 presents results of the first-in-human data on TruCARTMGC027 a universal CAR-T product developed using CRISPR-based technology for the treatment of adult relapsed/refractory T-cell acute lymphoblastic leukemia (ALL). Four of five patients had an MRD-negative response.
Abstract CT051 describes a small study of a bispecific CAR-T construct in children and young adults with relapsed/refractory ALL. Eight of 11 patients who completed treatment had objective responses (four MRD-negative complete responses and four partial responses).
Covid-19 and Cancer
A clinical Plenary Session taking place on Day 2 of the virtual meeting will be devoted to Covid-19 and cancer. Dr. Ribas will chair this session that will feature speakers from Wuhan, Italy, and New York City and cover experience in using oncology drugs to treat Covid-19 patients.
Some drugs used to treat cancer patients may be repurposed to treat the consequences of Covid-19. “This category benefits from the experience of cancer and hematologic treatment for similar complications, such as respiratory distress and cytokine release syndrome [CRS],” said Dr. Ribas.
According to Dr. Ribas, tocilizumab is used to treat CRS in patients treated with CAR-T. JAK inhibitors used to treat certain cancers are also being tested in patients with Covid-19 and respiratory distress. Other cancer drugs may also find a role in treating the complications of Covid-19.
“The confluence between cancer research and the field of virology should enable more rapid translation,” he said.
By John McCleery
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