Dana-Farber researchers present key studies at ASCO annual meeting

Dana-Farber Cancer Institute researchers are presenting dozens of research studies at the 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO). The studies will be presented online during the virtual scientific program taking place May 29-May 31. ASCO is the world’s largest clinical cancer research meeting, attracting more than 30,000 oncology professionals from around the world.

The findings show new treatments and diagnostic advances in breast and lung cancers, lymphoma, kidney, and many others, as well as looking at using video education to guide care, and racial and ethnic disparities in cancer care. Some of the research highlights include:

Interim analysis of ZUMA-5: A phase 2 study of axicabtagene ciloleucel in patients with relapsed/refractory indolent non-hodgkin lymphoma

Author: Caron Jacobson, MD

Abstract: 8008

The vast majority of patients with follicular lymphoma or marginal zone lymphoma – two slow-growing forms of non-Hodgkin leukemia – responded to and benefited from a novel CAR T-cell therapy in a recent clinical trial, Dana-Farber Cancer Institute investigators report. The 140 participants (124 with follicular lymphoma, 16 with marginal zone lymphoma) in the ZUMA-5 trial had received a median of three treatments for their disease prior to treatment with axicabtagene ciloleucel, a CAR T-cell therapy that targets CD19 receptors on cancerous cells. Ninety-three percent of the patients showed a response to the therapy, including 80% who had a complete response – an absence of detectable cancer following treatment. In patients with an initial complete response, 80% maintained that response after a median follow-up of 15.3 months. The most common adverse effects of the therapy were neutropenia, anemia, and decreased neutrophil count, which generally were manageable. The rate of high-grade neurotoxicity was 15%. Among patients with follicular lymphoma, 23% had no cytokine release syndrome, and the median time to onset was four days, which may allow for outpatient dosing in the future.

Tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB)

Author: Nancy Lin, MD

Abstract: 1005

In patients with HER2+ metastatic breast cancer that has spread to the brain, combining the HER2-inhibiting agent tucatinib with trastuzumab and capecitabine can significantly delay the advance of the disease in the brain and extend patients’ lives, a clinical trial led by Dana-Farber Cancer Institute investigators has demonstrated. The HER2CLIMB study compared the three-drug regimen to trastuzumab and capecitabine alone in 291 patients whose breast cancer had metastasized to the brain. Participants in the tucatinib group experienced a median of nine months before the brain metastases grew worse, compared to 4.2 months for the non-tucatinib group, and survived a median of 18.1 months compared to 12 months for the non-tucatinib group. Based on results of HER2CLIMB, the FDA granted approval of the three-drug regimen on April 17, 2020, for the treatment of adult patients with advanced inoperable or metastatic HER2+ breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

A multicenter phase 2 study of venetoclax plus dose-adjusted R-EPOCH (VR-EPOCH) for Richter’s syndrome

Author: Matthew S. Davids, MD, MMSc

Abstract: 8004

Adding a relatively new targeted drug, venetoclax, to a standard chemoimmunotherapy regimen has shown promising activity in Richter’s syndrome, a transformation of a more indolent disease, chronic lymphocytic leukemia, into an aggressive form of non-Hodgkin lymphoma (NHL) with a particularly poor prognosis, say researchers from Dana-Farber. There is no standard of care for treatment, but a commonly used regimen is R-EPOCH, a combination of four chemotherapeutic agents plus rituximab, a monoclonal antibody immunotherapy drug. Although R-EPOCH is highly effective for some forms of NHL, in Richter’s syndrome the rate of complete response is only about 20%, and the average survival is only three to six months.

Venetoclax, the first of a class of drugs known as BCL2 inhibitors, had a 43% overall response rate as a single agent in small cohort of patients with Richter’s syndrome in a phase 1 study. In the current study, venetoclax was combined with R-EPOCH (VR-EPOCH) with the rationale that the venetoclax may work as a “chemosensitizing” agent to help the chemotherapy be more effective. This single-arm, phase 2 investigator-initiated multicenter study enrolled 26 patients at Dana-Farber, MD Anderson, and Ohio State. In the 20 patients who began combination therapy, 16 (80%) responded, including 13 (65%) who had complete response as best response. Eight patients had allogeneic stem cell transplants, with the first such patient now still in complete remission over two and half years after completing transplant. Patients who were not transplant candidates could continue on venetoclax maintenance, and the longest such patient has now been in complete remission for over two years after completing the chemotherapy portion of the study. The side effects were typical of those seen with R-EPOCH alone, including infections and low blood counts.

Matthew S. Davids, MD, MMSc, is the principal investigator and first author of the study and said about two-thirds of the patients who started the VR-EPOCH combination achieved complete remission, far higher than the 20% achieved historically with R-EPOCH alone and this chemosensitization strategy will be further explored in additional studies in this patient population.

Idecabtagene vicleucel, a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma; initial KarMMa results

Author:Nikhil Munshi, MD

Abstract: 8503

A potential CAR T-cell therapy that targets a key plasma cell antigen on cancer cells produced deep and lasting responses in patients with relapsed and treatment-resistant multiple myeloma who had undergone several previous treatments, according to preliminary data from an international clinical trial led by Dana-Farber Cancer Institute researchers. The 128 patients in the KarMMa study were treated with idecabtagene vicleucel, a genetically engineered CAR T-cell therapy made from patients’ own T cells that targets the B-cell maturation antigen (BCMA) on myeloma cells. After a median follow-up of 13.3 months, 73.3% of participants had a partial or complete response to the therapy, and the median interval before the disease worsened was 8.6 months, both of which were higher at increased doses. The most common adverse effects were cytopenia (a low red blood cell count) and cytokine release syndrome, a common side effect of CAR T-cell therapies.

A randomized controlled trial of video education or in-person genetic counseling for men with prostate cancer

Author:Huma Q. Rana, MD

Abstract: 1507

This study compared a novel video education method with in-person genetic counseling in advance of genetic testing for men with potentially lethal prostate cancer and found no significant differences in acceptability of genetic testing. Although the study has not been completed, this randomized trial suggests that video education can be used to improve access to cancer genetics education and testing to patients who, for various reasons including the coronavirus pandemic, lack access to in-person genetic counseling.

Led by Huma Q. Rana, MD, and Mary-Ellen Taplin, MD, the trial, called ProGen, recruited men with potentially lethal prostate cancer. This includes metastatic disease, a high Gleason score, rising PSA (prostate specific antigen) after local therapy, diagnosis at age 55 or younger, and other factors. Rana found 13% of subjects had pathogenic or likely pathogenic variants in cancer susceptibility genes; 32% of subjects with a positive result had pathogenic variants were in BRCA1 and BRCA2. Identifying those variants through genetic testing may lead to targeted therapy and can guide cancer surveillance. Genetic testing is recommended to these patients, but access to genetic counseling and testing is limited by strained resources. The ProGen study examined a novel video pretest model aimed at providing access to genetic testing for men who have been traditionally underserved/unrepresented in cancer genetics clinics.

Over a two-year period, 662 men were randomized 3:1 to video education or genetic counseling in person. At the time of the intervention, most men agreed or strongly agreed that their assigned arm – video or in-person – was useful. The researchers concluded that both the novel video education modality and traditional genetic counseling “yielded high genetic testing uptake without significant differences in outcome measures of acceptability and satisfaction.”

US trends and racial/ethnic disparities in opioid access among patients with poor prognosis cancer near end of life

Author:Andrea Enzinger, MD

Abstract: 7005

Efforts to mitigate the opioid addiction crisis may have unintended consequences for cancer patients near the end of life, particularly for black patients and other racial/ethnic minorities. According to a recent Dana-Farber study, cancer patients’ access to opioids at the end-of-life has decreased substantially since 2007, with even greater declines among African Americans.

Andrea Enzinger, MD, is first author of this study which included 243,124 Medicare patients with poor prognosis cancers who died between 2007 and 2016. The analysis revealed that the proportion of cancer patients filling an opioid prescription in the 30 days before death or hospice enrollment fell from 41.7% to 35.7% over the study period, with greater decreases among black patients (39.3% to 29.8%) than white patients (42.2% to 36.5%). Use of long-acting opioids, which are important for managing severe cancer pain, also fell from 17% in 2007 to 12% in 2016. Blacks patients were also significantly less likely than white patients to be prescribed long-acting opioids and were prescribed significantly lower doses of opioids. Rates of emergency department visits for pain near the end of life increased from 13.2% to 18.8% over the study period. Again, black patients were significantly more likely than whites to receive care for their pain in an emergency department.

The researchers concluded that cancer patients’ access to opioids near the end-of-life decreased substantially from 2007 to 2016, while pain-related visits to emergency departments increased. Along with this trend, the scientists report that there are significant racial and ethnic disparities in opioid access, with black patients receiving fewer opioids at lower doses, and having more emergency-department-based care for pain near the end of life.

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