The American Society of Clinical Oncology (ASCO) is the leading professional organization for physicians and oncology professionals caring for people with cancer. Through its multidisciplinary network of almost 45,000 oncology professionals, ASCO seeks to provide high-quality resources in education, policy, and clinical research to cancer professionals to advance and improve care for patients with cancer.
The 2019 ASCO Annual Meeting took place from May 31 to June 4, in Chicago, Illinois. The conference brought together oncologists from all over the world to present groundbreaking research and scientific advances in cancer care. The focus of this year’s meeting was “Caring for Every Patient, Learning From Every Patient.”
Journal of Clinical Pathways staff was onsite to cover sessions and meet with presenters. Additional presentation coverage and interviews can be found online here.
Long-Term Survival Data of Trastuzumab Biosimilar vs Trastuzumab in HER2-Positive Breast Cancer
A presentation at the 2019 ASCO Meeting provided further support for the safety and efficacy profile of trastuzumab-dkst for patients with HER2-positive metastatic breast
HERITAGE was a multicenter, double-blind, randomized, parallel-group, phase 3 trial designed to evaluate the efficacy and safety of trastuzumab-dkst vs trastuzumab as first-line options for patients with HER2-positive metastatic breast cancer. Previously, overall response at week 24 and progression-free survival (PFS) at week 48 were reported.
Cornelius F Waller, PhD, University of Freiburg Medical Center (Germany), and colleagues randomized 500 patients (1:1) to trastuzumab-dkst or trastuzumab. Both patient groups received taxane after initial therapy. After 24 weeks, patients with responding and stable disease continued monotherapy per randomization. Safety and overall survival (OS) during maintenance, as well as through 36 months of follow-up, were reported at the ASCO Annual Meeting.
Among the total patient population, 343 received monotherapy after 24 weeks (trastuzumab-dkst, n=179; trastuzumab, n=164). A total of 128 patients discontinued monotherapy (trastuzumab-dkst, n=63; trastuzumab, n=65), and mean time to discontinuation was 19 months in both groups.
Dr Waller and colleagues reported that treatment-related adverse events during monotherapy were similar for trastuzumab-dkst (69%) and trastuzumab (73%). Most treatment-related adverse events were low grade, and serious adverse event rates were only 6% in both groups. The cumulative rates of treatment-related adverse events of special interest were similar for hypersensitivity, pulmonary, and cardiac events, they acknowledged.
Furthermore, researchers noted that at 36 months, 169 patients had received further lines of therapy with similar distribution of HER2-specific treatments, endocrine therapies, and chemotherapies. Median PFS was 11.1 months in both groups. Similarly, median duration of response was 9.9 and 9.8 months for trastuzumab-dkst and trastuzumab, respectively, and median OS was 35.0 and 30.2 months.
“Long-term safety data with similar median OS compared with originator trastuzumab further support the safety and efficacy profile of trastuzumab-dkst,” authors of the study concluded.
Community Oncology Palliative Care Program as an OCM Quality Improvement Effort
A palliative care program launched at Michigan Health Professionals—a large community oncology practice participating in the Oncology Care Model (OCM)—provided more care at home and at a lower cost for participating patients. This trend may be replicated in comparable community settings, according to the researchers.
At the 2019 ASCO Meeting, Adil Akhtar, MD, oncology division of Michigan Health Professionals, and colleagues presented on a palliative care program launched in October 2017. Palliative and end-of-life care was identified as one of the OCM quality improvement areas at the time.
A multidisciplinary palliative care team was led by board-certified palliative care and hospice physicians. Patients deemed appropriate for palliative care referral were identified by participating medical oncologists. Patients were then contacted by the palliative care team and, if they agreed to participate, a nurse practitioner would assess and follow the patients at home. Care was coordinated by the nurse practitioners in communication with the palliative care team and the primary medical oncologists.
To determine whether the palliative care program was helping Michigan Health Professionals’ performance in OCM performance period 3, last 30-day OCM program claims data was analyzed by Integra Connect.
Over a 12-month span from the launch of the program, a total of 273 patients were referred to the palliative care program. Fifty-eight patients were identified as having OCM episodes; of these, 36 patients had claims data through June 2018. Twenty patients accepted and engaged with palliative care, while 16 patients declined or were unable to reach for palliative care (comparison group).
After excluding drug and office costs, 30-day claims data showed that palliative care patients spent 17% less than their comparison counterparts ($93,000 vs $112,000, respectively). Similarly, palliative care was associated with lower acute facility costs, which accounted for 50% ($46,000) of reimbursement compared with 95% ($105,000) for the comparison group.
Furthermore, 80% of palliative care patients met the quality measure for OCM performance period 3, compared with 0% for those who declined palliative care.
Michigan Health Professionals’ palliative care program is reaching patients in OCM episodes, though the patient accrual numbers are still small and will continue to grow, Dr Akhtar assured Journal of Clinical Pathways in an interview. Nonetheless, the initial results are still promising and shed light on an important measure that community setting OCM participants can take to improve their care for patients.
Neurotoxicity From CAR T-Cell Therapy: Why It Happens, How to Manage It
At a Friday session at the 2019 ASCO Annual Meeting that discussed cytokine release syndrome (CRS) assessment and management, Bianca D Santomasso, MD, PhD, Memorial Sloan Kettering Cancer Center (New York, NY), spoke at length about neurotoxicity from CAR-T therapy, the second major toxicity from CAR T-cell infusion.
Her presentation covered the clinical manifestations of neurotoxicity, the correlations underlying why neurotoxicity happens, and new grading guidelines for management.
She first provided a clinical case study of severe neurotoxicity that demonstrated a few key observations: neurotoxicity can occur after CRS is completely resolved; tocilizumab does not resolve severe neurotoxicity; and corticosteroids may be used for management of severe neurotoxicity, although some cases resolve without them.
Previously, neurotoxicity had been lumped in the symptom list of CRS, but it has recently been identified as a distinct entity and is now referred to as immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS is characterized by global encephalopathy, aphasia, seizure/seizure-like activity, obtundation, tremor/myoclonus, and hallucinations. She noted that studies have shown that neurotoxicity is almost always reversible though.
Clinical factors impacting the risk of ICANS includes marrow disease percentage (acute lymphocytic leukemia), CAR T-cell dose, prior severe CRS, fludarabine-containing condition regimen, and abnormal past MRI brain scan/pre-existing neurologic comorbidities. Severe ICANS is correlated with higher peak CAR T-cell expansion in blood, earlier onset of fever, elevated serum cytokines, endothelial cell activation/brain microvascular compromise, blood-cerebral spinal fluid (CSF)-barrier breakdown, changes in MRI, and excitotoxins in CSF.
In terms of grading and assessment conventions, Dr Santomasso said there is a need for harmonization of CRS and neurotoxicity grading, as there is variation across clinical trials and different institutions. This makes it difficult to compare the safety of different products and hinders the ability to develop optimal strategies for management of toxicities. Also, some aspects of existing grading systems can be challenging to implement across centers.
She then discussed the consensus grading system for CRS and ICANS generated by experts with support from the American Society for Transplantation and Cellular Therapy in 2018. The guidelines propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The guidelines are meant to be used as a building block for developing management strategies, she noted.
Dr Santomasso concluded her presentation by noting that all of these recommendations and strategies should be supplemented by truly knowing your patient and your product. A team effort is required to handle the unique acute toxicities from CAR-T therapy.
Long-Term Survival Trends of Anti-Cancer Agents as Measured by ASCO-VF vs ESMO-MCBS
Anti-cancer agents have recently generated excitement with their ability to preserve long-term survival in some patients, represented by a “tail of the survival curve.” But, as traditional measures of clinical benefit may not accurately capture long-term survival, amendments to various valuation frameworks have been proposed to capture this benefit.
The purpose of this study was to determine how frequently immune checkpoint inhibitor vs non-immune checkpoint inhibitor anti-cancer agents displayed trends of long-term survival, as defined by the American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). The degree of agreement between ASCO and ESMO frameworks was also analyzed.
Authors from the Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto (Toronto, ON, Canada), began by identifying anti-cancer agents from phase 2 or 3 randomized controlled trials (RCTs) cited for clinical efficacy evidence in drug approval by the Food and Drug Administration (FDA) between January 2011 and March 2018. Data required for ASCO-VF and ESMO-MCBS were extracted. Difference in how often long-term survival bonuses were awarded were calculated in all RCTs, as well as immune checkpoint inhibitor and non-immune checkpoint inhibitor RCTs individually. Cohen’s Kappa statistic was calculated to evaluate agreement between ASCO-VF and ESMO-MCBS.
Overall, 100 RCTs were analyzed. RCTs were awarded ASCO-VF version 2 (v2) “tail of the curve” bonuses more often than ESMO-MCBS version 1.1 (v1.1) “immunotherapy-triggered” long-term plateau adjustments (45% vs 2.6%). Comparing to non-immune checkpoint inhibitor RCTs, immune checkpoint inhibitor RCTs were not more likely to receive ASCO-VF v2 bonuses/ESMO-MCBS v1.1 adjustments (P=.32/P=.40). Long-term survival agreement between the two frameworks was poor (kappa: 0.01; P=.50).
Based on their findings, authors concluded that the ASCO-VF v2 and ESMO-MCBS v1.1 may require additional refinement in order to accurately capture the benefit of long-term survival. Immune checkpoint inhibitor and non-immune checkpoint inhibitor agents may not preserve substantially different long-term survival populations.