By Alfred I. Neugut

This week we continue our reporting of interesting or important studies from this year’s meeting of the American Society of Clinical Oncology in Chicago. At this meeting the most important advances of the year are presented which will impact how cancer is treated going forward. Of course, you are getting my biases in what I consider interesting. Herewith some additional key studies:

• An important new modality for therapy over the past few years has been CAR-T (chimeric antigen receptor T cell) therapy, a form of immunotherapy. This has been making inroads for the past several years into the treatment of advanced hematologic malignancies. At this year’s meeting, two papers made a particular impression. The first study presented was for relapsed or refractory large B-cell lymphoma. Diffuse large B-cell lymphoma constitutes the largest fraction of non-Hodgkin lymphoma and can be variable but, overall, it is cured with conventional treatment in approximately 50% of cases. For those who fail this therapy, approximately an additional 20% will be cured with second-line chemotherapy. The reported study at ASCO randomized 359 patients who failed first-line therapy to receive CAR-T cell therapy with Axicabtagene Ciloleucil followed by autologous stem cell transplantation versus standard care. With a median follow-up of 47 months, the four-year progression-free survival was 41.8% for the CAR-T therapy versus 24.4% for standard therapy, an impressive improvement.
• A similar trial was undertaken in the setting of patients who had progressed after one to three lines of treatment with multiple myeloma, a generally incurable disease but with prolonged survival with current treatment methods. The CARTITUDE-4 trial randomized 419 patients from 16 countries with relapsed multiple myeloma to CAR-T cell therapy with ciltacabtagene autoleucel versus standard of care. After a median follow-up of 16 months, the MRD rate (minimal residual disease is highly predictive of future outcomes for multiple myeloma) in the intervention group was 60.6% compared to 15.6% for standard therapy, a remarkable difference.
• One of the trends in oncology is the reduction in reliance on the primary anatomic site of the cancer as a determinant for treatment. Instead, we have learned that the tumor markers can be equally if not more indicative of what the tumor is likely to respond to. Thus, while we have learned much from HER2 positivity in breast cancer, it develops that other cancers are also frequently positive for HER2, and guess what? If they are, then they would also respond to the same drugs, i.e., trastuzumab (Herceptin). Thus, it is now standard of care to test gastric cancer and colorectal cancer for this marker as well as other cancers, and to use Herceptin for those who are positive. This brings us to the DESTINY-Pan Tumor02 Study (who makes up these names?), led by investigators from MD Anderson Cancer Center in Houston. This was a study of 267 HER2-positive tumors that was agnostic of tumor site but included bladder, head and neck, cervical, lung, and biliary tract cancers. After treatment with a trastuzumab derivative, with a median follow-up of 10 months, the tumors shrank in 61% with a median duration of response of 22.1 months.
• We generally do so well with Hodgkin lymphoma that we sometimes forget that there still remains a fraction of patients who fail with the standard treatment. And since these are primarily adolescent and young adult patients, this is particularly tragic. For those with advanced Hodgkin lymphoma, brentuximab, a monoclonal antibody that targets a cell membrane protein (CD30), is added to the standard chemotherapy regimen AVD (Adriamycin [doxorubicin], vinblastine, dacarbazine). However, brentuximab, despite improving survival, adds significant toxicity. A study led by investigators from City of Hope Cancer Center in California randomized 194 patients with stage III-IV Hodgkin lymphoma to brentuximab-AVD versus AVD with nivolumab, one of the new immunotherapy drugs with a lesser spectrum of toxicities. With a median follow-up of 12 months, progression-free survival was 94% for the nivolumab group versus 86% for the brentuximab group. I suspect this will create a new standard of care.
• Ribociclib is an oral agent that targets and inhibits CDK4 and CDK6, which modulate cancer cell growth; it is used in conjunction with aromatase inhibitors for advanced hormone-receptor positive breast cancer that is HER2 negative. Under these circumstances, ribociclib, together with an aromatase inhibitor, significantly extends survival for women with metastatic breast cancer. Thus, a study led by Dennis Slamon of UCLA was conducted to determine whether to include it for women receiving adjuvant therapy—5,101 patients with hormone receptor-positive, HER2 negative breast cancer were randomized to receive either ribociclib in conjunction with hormonal therapy or hormonal therapy alone. At a median follow-up of 34 months, 7.4% of patients in the ribociclib arm had experienced a recurrence versus 9.2% of those in the hormonal therapy alone arm. The three-year disease-free survival was 90.4% for ribociclib versus 87.1% for the hormonal therapy alone group, a 25% reduction in the recurrence risk. The huge sample size necessary to assess the statistical significance of these small gains in benefit highlights how well we are doing overall with breast cancer.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.