Results of several phase 3 trials and dozens of other studies led by Dana-Farber researchers were presented online and in person June 3-7 at the 2022 Annual Meeting of the American Society of Clinical Oncology (ASCO), the world’s largest clinical cancer research meeting. Some of the research reports presented by Dana-Farber investigators include:
Improved progression-free survival in multiple myeloma patients following three-drug therapy with autologous stem cell transplant
Dana-Farber’s Paul Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center, presented results of a phase 3 study of a three-drug regimen (lenalidomide, bortezomib, and dexamethasone) in patients with newly diagnosed multiple myeloma eligible for autologous stem cell transplant.
The findings, presented during the plenary session on June 5, found that newly diagnosed patients treated with this triad of drugs (abbreviated as RVd) lived longer without their disease worsening if they received an autologous stem cell transplant soon after RVd therapy rather than if they had their stem cells collected for a possible future transplant. Patients who did not undergo an early transplant had a median progression-free survival (PFS) of 48 months. By comparison, those who received an early transplant had a median PFS of 68 months — or more than five years. However, the overall survival rate was virtually the same — about 85% — for both groups with a median follow-up time of 76 months.
“Our study provides important information about the benefits of transplant in the era of highly effective novel therapies and continuous maintenance, as well as the potential risks, to help patients and their physicians decide what approach may be best for them,” says Richardson.
Race, ethnicity, and poverty linked to worse outcomes in children treated for high-risk neuroblastoma
A study led by investigators from Dana-Farber/Boston Children’s Cancer and Blood Disorders Center found that children with high-risk neuroblastoma had worse outcomes if they were from certain racial/ethnic groups or were on public rather than private insurance, despite being treated in clinical trials with standardized protocols. The study shows that young patients from historically marginalized populations or from lower-income backgrounds had poorer five-year survival rates even when they were assigned to receive uniform initial treatment after diagnosis with high-risk neuroblastoma.
“These findings recapitulate what we have known for decades at the population level — children from historically marginalized groups are less likely to survive their cancer,” says Puja J. Umaretiya, MD, a clinical fellow in pediatric hematology/oncology at Dana-Farber/Boston Children’s. “They add an essential next layer to our understanding of racial and ethnic disparities in childhood cancer, and that is that enrollment on clinical trials is not enough to achieve racial and ethnic equity in survival.”
Targeted drug achieves 43% response rate in KRAS-mutated lung cancer
Investigators led by Pasi Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology, reported that nearly 43% of patients with non-small cell lung cancer (NSCLC) whose lung cancers harbored a specific KRAS gene mutation responded to the experimental drug adagrasib, and the targeted agent also showed activity against lesions in the brain that metastasized from the lung tumors.
Patients with a specific mutation known as KRASG12C who had previously received both chemotherapy and immunotherapy with a PD-1 immune checkpoint blocker had a 42.9% objective response rate and a median overall survival rate of 12.6 months. Notably, adagrasib treatment also achieved a 33.3% response rate in 33 patients who had stable metastatic lesions in the brain and central nervous system that had spread from the lung tumors. The results were simultaneously published in the New England Journal of Medicine.
Immunotherapy drug combination is safe with promising results in glioblastoma
A novel combination of two experimental cancer immunotherapy agents along with an immune checkpoint blocker is yielding promising results in patients with newly diagnosed glioblastoma brain tumors, according to a presentation of interim, two-year follow-up clinical trial data by a Dana-Farber neuro-oncologist at the ASCO meeting.
The data from the phase I/II open-label GBM-001 trial found that “a significant percentage of patients had a robust immune response” in the peripheral blood stream and the drug combination was very well tolerated, said David Reardon, MD, clinical director of the Center for Neuro-Oncology at Dana-Farber and coordinating principal investigator of the GMB-001 clinical trial that includes 52 patients with the highly aggressive and lethal glioblastoma brain tumor.
Patients whose tumors had a favorable-prognosis biomarker, methylated MGMT status, had a markedly better median survival of 32.5 months compared to historical 23 to 25-month median survival. Patients with the less-favorable unmethylated MGMT status had a median survival of 17.9 months compared to historical medians of 14 to 16-months in this group, which Reardon called a “modest improvement.” Reardan commented, “These data are encouraging, and they highlight that combination immunotherapy for this disease may be an effective strategy where single agent immunotherapy has not worked very well.”
Endocrine sensitivity test predicts survival benefit of dose-dense chemotherapy for patients with HR+ breast cancer, study finds
A new genomic test designed to measure endocrine sensitivity of estrogen receptor positive breast cancer has the potential to identify patients diagnosed with ER+ breast cancer who could benefit more from dose-dense chemotherapy, a regimen in which chemotherapy is administered more frequently than normal, when compared to non-dose dense regimens, research by Dana-Farber shows.
The investigators found that women with ER+ breast cancer that scores low for a biomarker called SET2,3 (i.e., indicating endocrine resistance) benefited far more from dose-dense chemotherapy than patients with higher scores. The results applied those to pre-and postmenopausal women.
If confirmed by future studies, the biomarker could be the basis for the first test for identifying which of these patients diagnosed with ER+ breast cancer stands to have the best responses to dose-dense chemotherapy, says study presenter Otto Metzger, MD, of Dana-Farber.
Study offers guidance for future trials of adjuvant therapy for patients with early HR+/HER2- breast cancer
To fully evaluate hormone-blocking therapy following surgery for patients with early-stage high-risk HR+/HER2- breast cancer, researchers should continue to track patients for at least five years after the completion of active treatment, according to a study reported by Dana-Farber’s Meredith Regan, ScD. The study also shows when planning post-surgical, or adjuvant, therapy for such patients, oncologists should carefully weigh the benefits and toxicities of available treatments, whether alone or in combination.
The study sought to clarify issues about the early, short-term effectiveness of drugs known as CDK4/6 inhibitors in adjuvant treatment of patients with high-risk hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer, after several clinical trials of such inhibitors in combination with endocrine therapy — drugs like tamoxifen or aromatase inhibitors, which deprive HR+ breast tumors of estrogen — have produced inconsistent early results and do not yet have long-term results available.
The monarchE trial found that combining the CDK4/6 inhibitor abemaciclib with endocrine therapy improved survival in the first two to three years after treatment, leading to abemaciclib’s approval for patients with early high-risk HR+/HER2- breast cancer. While the Penelope-B trial also showed an early treatment effect for the CDK4/6 inhibitor palbociclib plus endocrine therapy, that benefit disappeared after about four years. A third trial, dubbed PALLAS, found no survival benefit for palbociclib in combination with endocrine therapy.
By focusing on the years immediately following treatment in the endocrine therapy trials, researchers gained new insights into the risk of cancer recurrence during that period.
Patient-facing screening tool could increase detection of individuals with inherited cancer risk
Nearly one million people in the United States are affected by Lynch syndrome — a hereditary cancer condition with markedly elevated risk of gastrointestinal, endometrial, and other cancers. Most of them, however, are unaware of it, or find out only after they have developed cancer. A screening tool — the PREMM5 model, developed at Dana-Farber, can help rapidly identify people who should undergo germline genetic testing for Lynch syndrome. PREMM5 was designed to be completed by providers but in a new project, Dana-Farber investigators adapted the screening tool as a patient-facing questionnaire and embedded the tool in the electronic health record system.
In the project led by Chinedu Ukaegbu, MBBS, MPH, new gastrointestinal cancer patients seen at Dana-Farber were able to complete the PREMM5 screener survey remotely or in clinic waiting rooms. The screener collects information about the person’s sex, age, personal history of cancer, and history of certain cancers among relatives. From these answers, a mathematical model calculates the probability that the individual has inherited any of one of the five Lynch syndrome genes. It’s recommended that anyone whose risk is 2.5% or greater be referred for genetic counseling and testing to determine if they harbor a Lynch mutation.
Between June 2020 and December 2021, 35% of new gastrointestinal cancer patients completed the screening survey, and 367 of 1,504 (24%) had a positive PREMM5 score of 2.5% or greater. As a result of their positive screen, 102 of 367 patients (28%) received a genetic counseling referral. When tested, 13 patients had cancer-related pathogenic variants, including four with Lynch syndrome. The researchers concluded that this patient-facing PREMM5 risk assessment method is feasible and identified nearly one in four general gastrointestinal oncology patients as warranting genetic evaluation. However, they noted additional refinements are needed to increase the rate of screener completion and referral for those with positive screens.
Senior authors of the study are Nadine J. McCleary, MD, MPH, medical director of the Dana-Farber Patient Reported Data program, and Sapna Syngal, MD, MPH, director of gastroenterology at the Dana-Farber Brigham Cancer Center and founder of Dana-Farber’s Lynch Syndrome Center.
A full list of Dana-Farber Faculty Oral Presentations at the 2022 ASCO Annual Meeting is available here.