The ASCO20 Virtual Scientific Program was a landmark year for the field of geriatric oncology, featuring more than 300 research abstracts that presented data on older adults with cancer. Here, we discuss several high-impact studies investigating interventions that modify outcomes for this patient population.
Smith Giri, MD, MHS
Ishwaria M. Subbiah, MD, MS
Geriatric Assessment–Guided Interventions
Four major randomized controlled trials demonstrated the value of a geriatric assessment–guided intervention among older adults with cancer, arguing for their inclusion as a part of routine cancer care.
In the first study, Mohile et al examined the impact of providing a geriatric assessment summary and management recommendations to oncologists on high-grade treatment-related toxicities among older adults (70 years or older) with cancer.1 In this randomized controlled trial, more than 700 older adults with advanced solid tumors or lymphoma (stage III or IV) receiving chemotherapy and/or other agents with at least one geriatric assessment domain impairment were randomly assigned to the intervention vs usual care. Patients in the intervention arm had a lower risk of grade 3 to 5 toxicities (50% vs 61%; relative risk = 0.74; P < .01). Meanwhile, the 6-month overall survival rate was not significantly different in the two groups (71% vs 74%; P = .3).
In the second randomized controlled trial, Li et al reported on the impact of geriatric assessment–driven intervention among older adults (≥ 65 years) with cancer.2 In this study, 600 older adults were randomly assigned in a 2:1 ratio to either geriatric assessment–driven intervention (n = 398) or standard of care (n = 202). In the geriatric assessment–driven intervention arm, a multidisciplinary team led by a geriatric oncologist reviewed the geriatric assessment results and implemented interventions based on predefined triggers.
The primary endpoint was incidence of grade 3 to 5 chemotherapy-related toxicity, whereas the secondary endpoints included advance directive completion, emergency room visits, and unplanned hospitalizations. Compared with the standard of care, the geriatric assessment–driven intervention yielded a significantly lower incidence of grade ≥ 3 toxicity (50.5% vs 60.4%; P = .02) and a higher rate of advanced directive completion (24.1% vs 10.4%); there were no significant differences in the other secondary endpoints.
In the third study, Soo et al reported on the integrated geriatric assessment and treatment (INTEGERATE) study, a randomized, open-label study testing the impact of integrated oncogeriatric care on outcomes of older adults with cancer.3 Overall, 154 adults older than age 70 with cancer who were to receive systemic therapy were randomly assigned to geriatrician-led comprehensive geriatric assessment and management vs usual care. The primary outcome was health-related quality of life measuring using the Elderly Functional Index (ELFI) at 0, 12, 18, and 24 weeks; secondary outcomes included function, mood, health-care utilization, and survival.
As compared with the usual-care arm, those receiving geriatric assessment and management had significantly better health-related quality of life, with a maximal difference at week 18 (estimated marginal mean ELFI score 72 vs 58.7; P = .001). Additionally, the intervention arm had a lower rate of hospital admission and early treatment discontinuation, both statistically significant.
“As compared with the usual-care arm, those receiving geriatric assessment and management had significantly better health-related quality of life, with a maximal difference at week 18.”— Smith Giri, MD, MHS, and Ishwaria M. Subbiah, MD, MS
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Finally, Qian et al reported on the impact of a perioperative geriatric intervention on postoperative outcomes among older adults with gastrointestinal cancers undergoing surgery.4 In this randomized controlled trial, 160 older adults (≥ 65 years) undergoing cancer surgery were randomly assigned to perioperative geriatric intervention or usual care. In the intervention arm, a geriatrician conducted a geriatric assessment and made recommendations to the surgical/oncology teams. The primary endpoint was postoperative length of stay, whereas secondary endpoints included intensive care unit (ICU) utilization, 90-day readmission risk, and patient-reported symptom burden and depression.
No significant differences were found in the length of stay (7.2 vs 8.2 days, P = .32), ICU use (23% vs 32%, P = .23), or readmission rates (22% vs 25%, P = .65) in the intention-to-treat analysis. Patients in the intervention arm reported a lower symptom burden including depressive symptoms. A major limitation of this study was that just 30 of the 69 patients randomly assigned to the experimental arm completed the planned intervention. However, per-protocol analysis revealed promising trends; those in the intervention arm had a significantly shorter length of stay (5.9 vs 8.2 days, P = .02) and ICU use (13.3% vs 32.4%, P < .05).
These four prospective studies lay the groundwork for an evidence-based approach to assess older patients with cancer.
Additional Key Abstracts
Given the immune senescence associated with aging, concerns have been raised about the efficacy of immune checkpoint inhibitors among older adults with cancer.5 In an international metastatic renal cell cancer database consortium analysis, Araujo et al evaluated 397 older adults (≥ 70 years) treated with immune checkpoint inhibitors as monotherapy or as a combination therapy. Older adults had lower response rates when used as first-line therapy (24% vs 31%; P = .01), but not in subsequent lines of therapy (20% vs 20%). On multivariate analysis, older adults with metastatic renal cell cancer had no difference in the time to treatment failure and overall survival when compared with younger adults.
Another study,6 however, reported that compared with younger counterparts, patients at least 65 years of aged receiving an immune checkpoint inhibitor had a greater risk of developing pneumonitis than their younger counterparts (hazard ratio = 2.1; P = .04). These results underscore the importance of a risk/benefit evaluation when considering checkpoint inhibitor therapy among older adults with cancer.
The phase II PANDA study randomly assigned 185 older adults (≥ 70 years) with untreated RAS/BRAF wild-type metastatic colorectal cancer to receive FOLFOX (leucovorin, fluorouracil [5-FU], oxaliplatin) plus panitumumab vs 5-FU plus panitumumab.7 Although no formal comparison between the two arms was planned, the overall response rate (65 vs 57%) and the median progression-free survival appeared similar in the two arms (9.6 vs 9.1 months). Meanwhile, grade 3 or 4 toxicity was much lower with 5-FU/panitumumab, arguing that 5-FU/panitumumab might be a reasonable option in elderly patients with metastatic colorectal cancer and warrants further investigation in phase III trials.
In the treatment of Hodgkin lymphoma in the elderly, the phase I/II HALO study tested the safety and efficacy of an anthracycline-free regimen comprising brentuximab vedotin plus bendamustine. The investigators
reported a complete remission rate of 63%, and a 2-year overall survival of 83% along with an acceptable safety profile.8 Meanwhile, for older adults with acute myeloid leukemia who were ineligible for intensive chemotherapy, the phase III VIALE-C study randomly assigned patients to receive venetoclax plus low-dose cytarabine vs cytarabine alone.9 The study authors reported superior overall and complete response rates as well as overall survival
(median overall survival = 8.4 vs 4.1 months; P = .04).
Conclusion
The ASCO20 Virtual Scientific Program featured several practice-changing abstracts focused on older adults with solid and hematologic malignancies. Four major trials demonstrated improved outcomes among older adults with cancer who received integrated oncogeriatric management. These findings strongly support the integration of geriatric assessment and appropriate interventions into routine oncologic care for older adults with cancer.
Dr. Giri is Assistant Professor of Hematology/Oncology, Institute for Cancer Outcomes and Survivorship, Division of Hematology/Oncology, University of Alabama at Birmingham. Dr. Subbiah is Assistant Professor, Palliative, Rehabilitation & Integrative Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston.
DISCLOSURE: Drs. Giri and Subbiah reported no conflicts of interest.
REFERENCES
1. Mohile SG, Mohamed MR, Culakova E, et al: A geriatric assessment intervention to reduce treatment toxicity in older patients with advanced cancer: A University of Rochester Cancer Center NCI community oncology research program cluster randomized clinical trial. ASCO20 Virtual Scientific Program. Abstract 12009.
2. Li D, Sun CL, Kim H, et al: Geriatric assessment-driven intervention (GAIN) on chemotherapy toxicity in older adults with cancer: A randomized controlled trial. ASCO20 Virtual Scientific Program. Abstract 12010.
3. Soo WK, King M, Pope A, et al: Integrated geriatric assessment and treatment (INTEGERATE) in older people with cancer planned for systemic anticancer therapy. ASCO20 Virtual Scientific Program. Abstract 12011.
4. Qian CL, Knight HP, Ferrone CR, et al: Randomized trial of a perioperative geriatric intervention for older adults with cancer. ASCO20 Virtual Scientific Program. Abstract 12012.
5. Araujo DV, Wells C, Hansen AR, et al: Efficacy of immune-checkpoint inhibitors in the treatment of older adults with metastatic renal cell carcinoma (mRCC): An international mRCC database consortium analysis. ASCO20 Virtual Scientific Program. Abstract 5068.
6. Li M, Spakowicz D, Zhao S, et al: Inhaled corticosteroid use and risk of pneumonitis in patients treated with immune checkpoint inhibitors. ASCO20 Virtual Scientific Program. Abstract 3140.
7. Lonardi S, Schirripa M, Buggin F, et al: First-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS-BRAF wild-type metastatic colorectal cancer elderly patients: The PANDA study. ASCO20 Virtual Scientific Program. Abstract 4002.
8. Schiano de Colella JM, Viviani S, Rapezzi D, et al: Brentuximab vedotin and bendamustine as first-line treatment of Hodgkin lymphoma in the elderly (HALO Trial). ASCO20 Virtual Scientific Program. Abstract 8029.
9. Wei AH, Montesinos P, Ivanov V, et al: A phase III study of venetoclax plus low-dose cytarabine in previously untreated older patients with acute myeloid leukemia (VIALE-C): A six-month update. ASCO20 Virtual Scientific Program. Abstract 7511.
