By Christina Bennett, MS
The press conference this morning featured several studies from the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting that attendees won’t see until Sunday or Monday. Two in particular were the SANDPIPER trial for advanced breast cancer and IMpower131 trial for advanced lung cancer. Also, Silicon Valley startup GRAIL, Inc., showcased its cancer detection prototype by presenting data from their lung cancer substudy.
Cancer Detection Test, No Longer a “Pipedream” (Abstract LBA8501)
GRAIL, Inc., the biotech startup backed by billionaires Jeff Bezos and Bill Gates, is on a mission to develop a diagnostic blood test that can detect cancer early on, and according to preliminary results, the startup is on the right path.
“Two years ago, it was a pipedream,” said Geoffrey R. Oxnard, MD, Associate Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School, who presented the results from the lung cancer substudy. “It was completely just a brainstorm and had no data supporting it, and I didn’t believe this could be done. Today, we actually have data that show that this is really feasible.”
The data come from the large prospective trial Circulating Cell-free Genome Atlas (CCGA) Study (NCT02889978). The CCGA study aims to enroll 15,000 participants, 70% of which with a cancer diagnosis and 30% without, in the United States and Canada. To date, about 12,000 participants have been enrolled across 142 sites in the United States and Canada.
From the CCGA study, several substudies have been conducted, including a breast cancer substudy featured in the poster session this morning (Abstract 536) and the lung cancer substudy presented during the press conference. Two additional studies are slated for Monday (Abstract 12021; Abstract 12003).
The findings reported for the lung cancer substudy were based on 2,800 samples in a prespecified case-control study, which were divided into a training set and a test set. A total of 118 lung cancer cases and 561 non-cancer cases were evaluable in the training set. An independent test set was used for validation.
“This is not cancer genotyping where you’re looking in the blood for a key mutation and targeting that mutation,” said Dr. Oxnard. “This is cancer detection, and it requires a different approach.”
To detect cancer, the cell-free DNA was evaluated, and three assays were used: targeted sequencing, whole-genome sequencing (WGS), and whole-genome bisulfite sequencing (WGBS).
He explained that the white blood cells are also sequenced. “The white blood cells are rich with mutations, which can pollute the data and make you think that there’s cancer present in the cell-free DNA.”
The prototype assays had a low false positive rate (2%). The targeted assay had a sensitivity of 51% for early-stage lung cancer (stage I-IIIA) and 89% for late-stage cancer (stage IIIB-IV). The WGS assay had a sensitivity of 38% for early-stage lung cancer and 87% for late-stage lung cancer. The WGBS had a sensitivity of 41% for early-stage lung cancer and 89% for late-stage lung cancer.
“The opportunity, perhaps, with a test like this is it’s very specific for finding cancer,” said Dr. Oxnard. He stressed, “This is not a blood test. This is a sequencing method that shows promise and needs to be turned into a diagnostic.”
“The next step will be to optimize those assays and machine learning algorithms and validate in larger data sets,” Charlotte Arnold, spokeswoman for GRAIL, Inc., told OBR. “We also have an ongoing study called STRIVE, which is enrolling 120,000 women at the time of mammogram screening.”
The STRIVE study (NCT03085888) is more representative of how GRAIL’s cancer detection prototype would work in a general population because, unlike the CCGA study, the participants do not know if they have cancer.
“We are hoping to complete enrollment by the end of the year, and then we need at least a year’s follow-up before we start to report results,” said Arnold.
SANDPIPER, a “Modest Step Forward” (Abstract 1006)
The phase III SANDPIPER trial in women with advanced breast cancer showed that the investigational agent taselisib slowed tumor growth and extended progression-free survival (PFS) by 2 months when combined with standard hormone therapy fulvestrant. Overall survival data have not been reported yet.
This is the first placebo-controlled, randomized trial to evaluate the efficacy and the safety of taselisib when added to fulvestrant in patients with advanced disease, asserted leady study author José Baselga, MD, PhD, Physician-in-Chief at Memorial Sloan Kettering Cancer Center.
Taselisib, a PI3K inhibitor, targets the PIK3CA mutation. Only two drugs are currently FDA approved in this class, and both are for hematological malignancies.
“This is a very appealing target,” said ASCO Expert Harold Burstein, MD, PhD. “It’s a mutation that is probably the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”
A total of 516 postmenopausal women with ER-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer were enrolled in the study. Participants were randomized to receive taselisib plus fulvestrant or fulvestrant plus placebo.
The trial met its primary endpoint: The median PFS was 2 months longer for the investigational agent arm (7.4 months) vs the placebo arm (5.4 months) (HR=0.70; P=.0037). The overall response rate was higher for the investigational agent arm (28%) than the placebo arm (11.9%) (P=.0002). Participants in North America and Europe who received taselisib had an even longer median PFS, 7.9 months compared to 4.5 months in the placebo arm.
For participants in the investigational agent arm, the most common severe side effects were diarrhea, colitis, and high blood sugar. Participants in the investigational arm were also more likely to discontinue treatment as a result of side effects. Seventeen percent of participants who received taselisib stopped treatment compared to only 2% in the placebo arm.
“It’s a modest step forward, but it’s an important step forward because it does suggest that we can effectively target the pathway and hopefully this gives us something we can build on so that we can use a targeted and precision approach in this very common type of breast cancer subtype,” said Dr. Burstein.
IMpower131 Met Co-Primary Endpoint, Technically (Abstract LBA9000)
Initial findings from the IMpower131 trial show the addition of PD-L1 inhibitor atezolizumab to chemotherapy extended median PFS by about three weeks for participants with advanced squamous non–small-cell lung cancer (NSCLC).
“Squamous non–small-cell lung cancer remains a very difficult to treat disease and there have been very limited new treatment options presented to us over the last few decades,” said lead study author Robert Jotte, MD, PhD, Medical Director and Co-Chair, USON Thoracic Committee, Rocky Mountain Cancer Centers. “Approximately 25 to 30 percent of patients with non–small cell lung cancer have tumors that indeed can be classified as squamous cell carcinomas.”
For this patient population, he noted, “First-line standard of care remains primarily platinum-based chemotherapy.”
The IMpower131 study had an all-comer design and enrolled 1,021 chemotherapy-naïve patients with stage IV squamous NSCLC. Any level of PD-L1 expression was accepted.
Patients were randomized to one of three arms. Arm A participants received atezolizumab plus carboplatin and paclitaxel. Arm B participants received atezolizumab plus carboplatin and nab-paclitaxel. Arm C served as the control and participants received carboplatin and nab-paclitaxel alone.
Only results for Arm B and Arm C were presented.
Median PFS was 6.3 months in Arm B (atezolizumab plus chemotherapy) and 5.6 months in Arm C (chemotherapy alone) (HR 0.71; P=0.0001).
For the interim analysis, the difference in overall survival was not statistically significant (14 months for Arm B vs 13.5 months for Arm C).
“The overall survival results are immature,” commented ASCO Expert David Graham, MD. “We hope that the results from progression-free survival translate to improved overall survival. If and when that's shown, I think we’ll clearly have a new standard of care for the frontline treatment of squamous cell non-small cell lung cancers.”
Tomorrow morning we’ll learn the preliminary results for a trial very similar to IMpower131, KEYNOTE-407. The difference is KEYNOTE-407 is evaluating pembrolizumab plus chemotherapy.