ALEXANDRIA, Va. - Two studies from the inaugural ASCO Plenary Series session will highlight the latest practice-changing results in advanced melanoma and digital symptom monitoring. The studies will be presented in a live broadcast session on November 16, 2021, at 3:00 PM ET. View the session recording (you must log in with an asco.org username and password to access the recording).
Immunotherapy Followed by Targeted Therapy Leads to Better Overall Survival for Patients With Advanced Melanoma With BRAF Mutation
ASCO Expert Perspective
“The study results from DREAMseq answer one of the most important clinical questions in our care of patients with advanced melanoma. For patients with melanoma with BRAFV600 mutation who have not received prior therapy, the results clearly show better overall survival when combination immunotherapy is selected first. In an era of remarkable advances for patients with melanoma, this study is an important addition to understanding the best approach to provide the very best care,” said ASCO Expert Lynn Schuchter, MD, FASCO.
For patients with advanced metastatic melanoma with BRAFV600 mutation, starting treatment with the immune checkpoint inhibitor combination of nivolumab/ipilimumab (N/I) followed by targeted therapy with dabrafenib/trametinib (D/T) resulted in greater overall survival when compared to the converse sequence. These research findings from the DREAMseq trial were presented during the inaugural session of the American Society of Clinical Oncology (ASCO) Plenary Series. These findings challenge current standards of care as many patients currently receive the targeted therapy combination first.
According to the lead author, about 45% of patients have a melanoma with BRAF mutations. This type of melanoma is relatively more common in younger patients. In the study:
- Eligible patients with advanced metastatic melanoma with BRAFV600 mutation who had not previously received systemic treatment were stratified by ECOG Performance Status 0 or 1 and lactate dehydrogenase (LDH) level and randomized 1:1 to receive Step 1 with either N/I (Arm A) or D/T (Arm B) and if disease progression occurred were then enrolled into Step 2 receiving the alternate therapy, D/T (Arm C) or N/I (Arm D).
- Long-term overall survival was higher with the sequence of therapies starting with the immunotherapy combination (Arm A) followed by the targeted therapy combination (Arm C) compared to the converse sequence.
- The two-year overall survival rate for patients starting with Arm A was 72% and for those starting with Arm B was 52%.
- Increased overall survival was first seen after 10 months, indicating the importance of switching to targeted therapy salvage in the small percentage of patients who had rapid progression on initial N/I therapy.
- Even though the N/I regimen has toxicities that required stopping therapy in many patients, a high percentage of patients achieved durable remissions.
“Our findings establish definitively that even for this oncogene driven tumor that the sequence beginning with immunotherapy—rather than targeted therapy—produces better overall survival for the vast majority of patients,” said lead author Michael B. Atkins, MD. “This is practice-changing because many patients, especially in the community oncology setting, receive targeted therapy as their initial treatment.”
From the November 2021 ASCO Plenary Series: DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG-ACRIN EA6134, Michael B. Atkins, et al. SCROLL DOWN TO VIEW FULL EMBARGOED ABSTRACT
Digital Symptom Monitoring Using Patient-Reported Data Helps Improve Symptom Control and Physical Function of Patients During Cancer Treatment
ASCO Expert Perspective
"These results suggest a relatively simple approach to improving how we care for patients with advanced cancer receiving treatment and a range of future applications to further improve how oncologic care is delivered,” said ASCO Expert Robert Dreicer, MD, MS, MACP, FASCO.
A digital symptom monitoring system in which patients undergoing cancer treatment report symptoms through weekly at-home surveys led to better symptom control and physical function, according to research presented during the inaugural session of the American Society of Clinical Oncology (ASCO) Plenary Series. In the study:
- A total of 52 United States-based community oncology practices were randomized 1:1 to digital symptom monitoring with patient-reported outcome (PRO) surveys or to usual care control. The study cohort included 1,191 patients with 593 patients at PRO practices and 598 patients at control practices.
- At the PRO practices, participants were invited to complete a weekly survey either by web or automated telephone system for up to one year. The survey included questions about nine common symptoms, performance status, and falls.
- Severe or worsening symptoms triggered electronic alerts to care team nurses, and reports showing symptom data over time were available to oncologists during in-person or telehealth visits.
- Enabling patients to report their symptoms and side effects directly to their cancer care team between visits led to improved communication with the team, better symptom management, and improved quality of life:
- Compared to patients at the control practices, clinically meaningful benefits were experienced in physical function (measured by the EORTC QLQ-C30, a questionnaire assessing health status over the previous week) by 13.8% more patients at PRO practices, in symptom control (nausea/vomiting, pain, dyspnea, constipation, diarrhea, insomnia, appetite loss, fatigue) by 16.1% more patients at PRO practices, and in health-related quality of life (a combination of function and symptom scores) by 13.4% more patients at PRO practices.
- Patients completed over 91% of expected surveys. Care team nurses responded to notifications about severe or worsening symptoms 59% of the time, most commonly by calling patients at home to counsel them on symptom management, add supportive medicines, or to set up new appointments.
“This national trial provides evidence that a simple technology asking patients about their symptoms is feasible, significantly improves symptom management, and yields better clinical outcomes,” said lead author Ethan Basch, MD, MSc. “For this type of system to work, it is essential to have not only high patient participation but a strong commitment from the health care team.”
From the November 2021 ASCO Plenary Series: Digital symptom monitoring with patient-reported outcomes in community oncology practices: A U.S. national cluster randomized trial, Ethan Basch, et al. SCROLL DOWN TO VIEW FULL EMBARGOED ABSTRACT
ATTRIBUTION TO THE ASCO PLENARY SERIES IS REQUESTED IN ALL COVERAGE.
Abstract 356154: DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG-ACRIN EA6134.
Authors: Michael B. Atkins, Sandra J. Lee, Bartosz Chmielowski, Antoni Ribas, Ahmad A. Tarhini, Jedd D. Wolchok, John M. Kirkwood; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC; Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA; Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA; University of California Los Angeles, Los Angeles, CA; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Medical Oncology, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, NY; University of Pittsburgh Medical Center, Pittsburgh, PA
Background: Combinations of immune checkpoint inhibitors (CPI) blocking PD-1 and CTLA-4 or BRAF/MEK inhibitors have both shown significant antitumor efficacy and overall survival (OS) benefit in patients (pts) with BRAFV600-mutant metastatic melanoma (MM), leading to broad regulatory approval. Little prospective data exists to guide the choice of one over the other as initial therapy or the preferred treatment sequence in this population. The DREAMseq Trial was designed to compare the efficacy and toxicity of the sequence of nivolumab/ipilimumab (N/I) followed by dabrafenib/trametinib (D/T) to the converse sequence.
Methods: Eligible pts with treatment-naive BRAFV600-mutant MM were stratified by ECOG Performance Status (PS) 0 or 1 and LDH level and randomized 1:1 to receive Step 1 with either N/I (Arm A) or D/T (Arm B) and at disease progression (PD) were enrolled in Step 2 receiving the alternate therapy, D/T (Arm C) or N/I (Arm D), respectively. Pts received N (1mg/kg)/I (3 mg/kg) q3 wks x 4 doses followed by N 240 IV q2 wks for up to 72 wks (Arms A and D) or D 150 mg po BID and T 2 mg po qD until PD (Arms B and C). In 2019, investigators were given the option to use alternate induction dosing of N (3mg/kg)/I (1 mg/kg) q3 wks x 4 doses for Arms A and D. Cycles were every 6 wks and imaging was obtained at baseline and q12 wks on each arm. Primary endpoint was 2-year OS. At the 4th Interim Analysis with 59% of pts being 2 yrs from enrollment, the DSMC and NCI CTEP recommended halting accrual and releasing the data.
Results: Beginning 7/2015, 265 out of a proposed 300 pts were enrolled (133 Arm A and 132 Arm B). Median age was 61 (25-85) and 63% were male. Demographics for Arm A and B were balanced with 67% PS 0 and 60% with normal LDH. As of 7/16/21, at a median follow-up of 27.7 mos, 27 pts had switched to Arm C and 46 to Arm D. Overall Grade 3+ toxicity was 60% in Arm A and 52% in Arm B. Grade 5 treatment-related AEs included 2 on Arm A and 1 on Arm C. ORR to date is: Arm A 46% (52/113), Arm B 43% (49/114), Arm C 48% (11/23) and Arm D 30% (8/27). 37/42 assessed pts in Arm A and 19/37 in Arm B remain in response. Median DOR: Arm A- Not reached; Arm B-12.7 mos (95% CI: 8.2, -) (p <0.001). There were 100 deaths (Arm A to C- 38/Arm B to D- 62). 2-yr OS rate for those starting with Arm A was 72% (95% CI: 62-81%) and for Arm B 52% (95% CI: 42-62%) (log-rank p= 0.0095). PFS showed a trend in favor of Arm A (log-rank p=0.054). Both the PFS and OS curves show a biphasic pattern with Arm B being above Arm A until 6 and 10 mos, respectively. For the 115 pts with documented progression on Step 1 (Arm A-44/Arm B-71), 60 (52%) had registered for Step 2. The principal reason for not enrolling on Step 2 was death from PD within 6 mos (Arm A:15/23; Arm B: 25/32).
Conclusions: For pts with advanced BRAFV600-mutant MM, the treatment sequence beginning with the CPI combination of N/I resulted in superior OS, which became evident at 10 mos, with longer Step 1 DOR and more ongoing responses than the treatment sequence beginning with D/T.
Abstract 349527: Digital symptom monitoring with patient-reported outcomes in community oncology practices: A U.S. national cluster randomized trial.
Authors: Ethan Basch, Deborah Schrag, Jennifer Jansen, Sydney Henson, Angela M. Stover, Patricia Spears, Mattias Jonsson, Allison Mary Deal, Antonia Vickery Bennett, Gita Thanarajasingam, Bryce Reeve, Claire Frances Snyder, Deborah Bruner, David Cella, Lisa A. Kottschade, Jane Perlmutter, Robert S. Miller, Jon F. Strasser, Dylan M. Zylla, Amylou C. Dueck; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Dana-Farber Cancer Institute, Boston, MA; Lineberger Comprehensive Cancer Center at University of North Carolina at Chapel Hill, Chapel Hill, NC; Cancer Information and Support Network, Raleigh, NC; University of North Carolina at Chapel Hill, Chapel Hill, NC; University of North Carolina, Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Mayo Clinic, Division of Hematology, Rochester, MN; Duke University School of Medicine, Durham, NC; Johns Hopkins University School of Medicine, Baltimore, MD; Winship Cancer Institute at Emory University, Atlanta, GA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; Mayo Clinic, Rochester, MN; Gemini Group, Ann Arbor, MI; American Society of Clinical Oncology’s CancerLinQ, Alexandria, VA; Joint Center for Radiation Therapy, Boston, MA; Park Nicollet/HealthPartners, Minneapolis, MN; Mayo Clinic, Scottsdale, AZ
Background: Symptoms are common during cancer care but often go undetected. Digital systems that elicit patient-reported outcomes (PRO) surveys may detect symptoms early and prompt clinicians to intervene, thereby alleviating suffering and averting complications.
Methods: In a cluster-randomized trial, U.S.-based community oncology practices were randomized 1:1 to digital symptom monitoring with PRO surveys, or to usual care control. Patients receiving systemic treatment for metastatic cancer were eligible. At PRO practices, participants were invited to complete a weekly survey via web or automated telephone system for up to one year, including questions about nine common symptoms, performance status, and falls. Severe or worsening symptoms triggered electronic alerts to care team nurses, and reports showing longitudinal symptom data were available to oncologists at visits. Pre-specified secondary outcomes included impact on physical function, symptom control, and health-related quality of life (HRQL). The primary outcome of survival is not yet mature.
Results: At 52 practices, 1,191 patients were eligible and enrolled (593 PRO; 598 control). Clinically meaningful benefits were experienced in physical function by 13.8% more patients with PRO versus control (P=0.009); symptom control by 16.1% (P=0.003); and HRQL by 13.4% (P=0.006). Mean changes from baseline were superior with PRO versus control for physical function (mean difference 2.47, 95% CI 0.41-4.53; P=0.02), symptom control (2.56, 0.95-4.17; P=0.002), and HRQL (2.43, 0.90-3.96; P=0.002). Patients completed 20,565/22,486 (91.5%) of expected weekly PRO surveys.
Conclusions: Digital symptom monitoring during cancer treatment confers clinical benefits.
Founded in 1964, the American Society of Clinical Oncology, Inc. (the Society) is committed to the principle that knowledge conquers cancer. Together with the Association for Clinical Oncology, ASCO® represents nearly 45,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of high quality and equitable patient care, ASCO works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. Conquer Cancer, the ASCO Foundation, supports the Society by funding groundbreaking research and education across cancer’s full continuum. Learn more at www.ASCO.org, explore patient education resources at www.Cancer.Net, and follow us on Facebook, Twitter, LinkedIn, Instagram, and YouTube.