Alliance A151945: Accrual and characteristics of adolescent and young adult patients in Alliance trials from 2000 to 2017.

BACKGROUND: Identifying patient- and disease-specific characteristics associated with clinical trial enrollment of adolescents and young adults (AYAs) with cancer may target efforts to improve accrual. METHODS: Alliance for Clinical Trials in Oncology (Alliance) trials opened from January 1, 2000, and closed before January 1, 2018, for common AYA cancers were identified. Proportions of AYAs (aged 18-39 years old) versus non-AYAs (aged ≥40 years old) enrolled by cancer type were summarized by descriptive statistics. Among studies with ≥20 AYAs enrolled, demographic and disease characteristics of AYAs versus non-AYAs were compared with χ2 and Kruskal-Wallis tests. A qualitative review was also conducted of therapeutic trials included in analysis in PubMed through December 31, 2021, that reported AYA-specific survival. RESULTS: Among 188 trials enrolling 40,396 patients, AYAs represented 11% (4468 of 40,396) of accrual. AYA accrual varied by cancer type (leukemia, 23.6%; breast, 9.9%; lymphoma, 14.8%; colorectal, 6.2%; central nervous system, 8.1%; melanoma, 11.8%; sarcoma, 12%). Across ages, the proportion of Black and Hispanic patients enrolled was 1%-10%. Compared to non-AYAs, AYAs in breast and colorectal cancer trials were less likely to be White and more likely to be Hispanic. Disease characteristics differed by age for selected trials. Two trials reported AYA-specific survival, with no significant differences observed by age. CONCLUSIONS: AYA accrual to Alliance trials was comparable to or exceeded population-based, age-specific prevalence estimates for most cancer types. Greater proportional representation of Hispanic and non-White patients among AYAs reflects US demographic trends. The small number of minority patients enrolled across ages underscores the persistent challenge of ensuring equitable access to trials, including for AYAs.

A pilot randomized, placebo-controlled, double-blind study of omega-3 fatty acids to prevent paclitaxel-associated acute pain syndrome in breast cancer patients: Alliance A22_Pilot2.

PURPOSE: Paclitaxel is associated with an acute pain syndrome (P-APS- and chronic chemotherapy-induced peripheral neuropathy (CIPN). P-APS is associated with higher risk of CIPN. Omega-3 fatty acids have well-established anti-inflammatory and neuroprotective properties. The primary purpose of this pilot study was to assess whether omega-3 fatty acids could decrease P-APS and thus CIPN. METHODS: Patients scheduled to receive weekly paclitaxel for breast cancer were randomized to receive 4 g of omega-3 acid ethyl esters (Lovaza) or placebo, beginning 1 week prior and continued until paclitaxel was stopped. Patients completed acute pain questionnaires at baseline, daily after each treatment, and 1 month after completion of therapy. RESULTS: Sixty patients (49 evaluable) were randomized to treatment versus placebo. Seventeen (68.0%) patients receiving the omega-3 fatty acids intervention experienced P-APS, compared to 15 (62.5%) of those receiving placebo during the first week of treatment (p = 0.77). Over the full 12-week study, 21 (84.0%) patients receiving the omega-3 fatty acid intervention experienced P-APS, compared to 21 (87.5%) of those receiving placebo (p = 1.0). Secondary outcomes suggested that those in the intervention arm used more over-the-counter analgesics (OR: 1.65, 95% CI: 0.72-3.78, p = 0.23), used more opiates (OR: 2.06, 95% CI: 0.55-7.75, p = 0.28), and experienced higher levels of CIPN (12.8, 95% CI: 7.6-19.4 vs. 8.4, 95% CI: 4.6-13.2, p = 0.21). CONCLUSIONS: The results of this pilot study do not support further study of the use of omega-3 fatty acids for the prevention of the P-APS and CIPN. TRIAL REGISTRATION: Number: NCT01821833.

Disparities in older adult accrual to cancer trials: Analysis from the alliance for clinical trials in oncology (A151736).

BACKGROUND: Older adults are under-represented in cancer clinical trials. However, it remains unclear which types of trials under-enroll aging patients. We aimed to identify associations between trial characteristics and disparate enrollment of older adults onto trials sponsored by the Alliance for Clinical Trials in Oncology (Alliance). METHODS: Actual age ≥ 65 percentage and trial data were extracted from the Alliance closed study list. Each trial, based on its cancer type and years of enrollment, was assigned an expected age ≥ 65 percentage extracted from the Surveillance, Epidemiology, and End Results (SEER) US population-based database. Enrollment disparity difference (EDD), the difference between the expected age ≥ 65 percentage and the actual age ≥ 65 percentage, was calculated for each trial. Linear regression determined trial variables associated with larger EDDs and variables with an overall association p-value <0.20 were included in a multivariable fixed-effects linear model. RESULTS: The median age of 66,708 patients across 237 trials was 60 years (range 18-102). The average actual age ≥ 65 percentage enrolled per trial was lower than each trial's expected age ≥ 65 percentage average (39% vs. 58%; EDD 19, 95% CI 17.1-21.3%, p < 0.0001). In multivariable analyses, non-genitourinary (GU) cancer types (p < 0.001), trimodality+ trials (estimate 8.78, 95%CI 2.21-15.34, p = 0.009), and phase 2 trials (estimate 4.43 95% CI -0.06-8.91; p = 0.05) were all associated with larger EDDs. CONCLUSIONS: Disparate enrollment of older adults is not equal across cancer trials. Future strategies to improve older adult inclusion should focus on trial types associated with the highest disparate enrollment.

How Did a Multi-Institutional Trial Show Feasibility of Electronic Data Capture in Older Patients With Cancer? Results From a Multi-Institutional Qualitative Study (Alliance A171902).

PURPOSE: New technology might pose problems for older patients with cancer. This study sought to understand how a trial in older patients with cancer (Alliance A171603) was successful in capturing electronic patient-reported data. METHODS: Study personnel were invited via e-mail to participate in semistructured phone interviews, which were audio-recorded and qualitatively analyzed. RESULTS: Twenty-four study personnel from the 10 sites were interviewed; three themes emerged. The first was that successful patient-reported electronic data capture shifted work toward patients and toward study personnel at the beginning of the study. One interviewee explained, "I mean it kind of lost all advantages…by being extremely laborious." Study personnel described how they ensured electronic devices were charged, wireless internet access was up and running, and login codes were available. The second theme was related to the first and dealt with data filtering. Study personnel described high involvement in data gathering; for example, one interviewee described, "I answered on the iPad, whatever they said. They didn't even want to use it at all." A third theme dealt with advantages of electronic data entry, such as prompt data availability at study completion. Surprisingly, some remarks described how electronic devices brought people together, "Some of the patients, you know, it just gave them a chance to kinda talk about, you know, what was going on." CONCLUSION: High rates of capture of patient-reported electronic data were viewed favorably but occurred in exchange for increased effort from patients and study personnel and in exchange for data that were not always patient-reported in the strictest sense.

Cisplatin-associated neuropathy characteristics compared with those associated with other neurotoxic chemotherapy agents (Alliance A151724).

PURPOSE: The current project was developed to obtain natural history information regarding cisplatin-induced peripheral neuropathy in males with testicular/germ cell cancers and to compare such neuropathy data with similarly obtained data in patients receiving other chemotherapy drugs in similarly conducted clinical trials. METHODS: Patients without baseline neuropathy symptoms, who were initiating cisplatin-based chemotherapy, completed the EORTC CIPN 20 patient-reported instrument to evaluate chemotherapy-induced peripheral neuropathy (CIPN). Results were compared with EORTC CIPN 20 data obtained from independent study sets regarding patients receiving (1) paclitaxel, (2) combined paclitaxel and carboplatin, (3) oxaliplatin, or (4) a combination of doxorubicin and cyclophosphamide (AC). The last study set of patients on AC was selected to evaluate the use of EORTC CIPN 20 data in patients receiving chemotherapy not known to cause CIPN. RESULTS: Cisplatin-induced neuropathy was more similar to neuropathy in patients receiving oxaliplatin than in those receiving paclitaxel. The cisplatin and oxaliplatin groups exhibited the coasting phenomenon and more prominent upper extremity symptoms than lower extremity symptoms during chemotherapy administration weeks. In contrast, paclitaxel-treated patients did not, on average, exhibit the coasting phenomenon; additionally, lower extremity symptoms were more prominent during the weeks when paclitaxel was administered. Cisplatin-induced neuropathy was less severe than was seen in patients in the other two groups, potentially because the cisplatin-receiving patients were younger. Patients receiving AC did not report substantial EORTC CIPN 20 changes. CONCLUSION: Understanding neuropathy similarities and differences with various chemotherapy agents may help elucidate CIPN processes and facilitate means to prevent and/or treat established CIPN. TRIAL REGISTRATION: NCT02677727.

A randomized, double-blind, placebo-controlled trial of testosterone for treatment of postmenopausal women with aromatase inhibitor-induced arthralgias: Alliance study A221102.

PURPOSE: To evaluate the efficacy of testosterone supplementation for improving aromatase inhibitor musculoskeletal symptoms (AIMSS). METHODS: Postmenopausal women experiencing moderate-to-severe arthralgias while taking adjuvant aromatase inhibitors for breast cancer were enrolled in this trial. Initially, patients were randomly allocated to receive either a subcutaneous testosterone pellet versus a placebo pellet. Due to slow accrual, the protocol was modified such that additional participants were randomized to receive either a topical testosterone gel or a placebo gel. Changes in patient-reported joint pain were compared between patients receiving testosterone and those receiving placebo using a two-sample t test. Changes in hot flashes and other vasomotor symptoms were also analyzed. Further analyses were conducted to evaluate whether 27 single nucleotide polymorphisms (SNPs) in 14 genes previously associated with AIMSS were associated with testosterone supplementation benefit. RESULTS: While 64% of patients reported an improvement in joint pain at 3 months, there were no significant differences in average pain or joint stiffness at 3 or 6 months between testosterone and placebo arms. Patients receiving testosterone did report improvements in strength, lack of energy, urinary frequency, and stress incontinence (p < 0.05). The subset of patients receiving subcutaneous testosterone also experienced improvements in hot flashes and mood swings. An inherited variant (rs7984870 CC genotype) in TNFSF11 was more likely to be associated with improvements in hot flashes in patients receiving testosterone. CONCLUSION: The doses of testosterone supplementation used in this study did not significantly improve AIMSS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01573442.

Toxicity and survival outcomes in older adults receiving concurrent or sequential chemoradiation for stage III non-small cell lung cancer in Alliance trials (Alliance A151812).

INTRODUCTION: Optimal treatment for older adults with stage III non-small cell lung cancer (NSCLC) remains unclear. Here we hypothesized that sequential chemoradiation therapy (sCRT) is better tolerated than concurrent (cCRT) but confers acceptable efficacy. We evaluated these strategies in older adults utilizing Alliance for Clinical Trials in Oncology data. MATERIALS AND METHODS: Pooled analyses from 6 first-line stage III NSCLC CRT trials (Cancer and Leukemia Group B 8433, 8831, 9130, 30106, 30407, 39801) were used to compare toxicity and survival outcomes with cCRT versus sCRT in patients age ≥ 65 years. Grade 3-5 adverse events (AEs), progression-free and overall survival (PFS; OS) are reported with adjustment for covariates. RESULTS: Four hundred older adults, of whom 106 (26.5%) had received sCRT and 294 (73.5%) had received cCRT, comprised the cohorts. Virtually all had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (99%). More grade 3-5 AEs were observed at any time-point with cCRT than sCRT (94.2% versus 86.8%; 95% confidence interval for difference in proportions, 1.3%, 15.5%) and this finding remained after adjusting for length of study treatment (P = 0.018). Comparable PFS and OS were observed with sCRT versus cCRT (median: 8.0 versus 9.2 months; median: 11.9 versus 13.4 months, respectively) even after adjustment for age, sex, ECOG PS, body mass index, pretreatment weight loss, stage, and cisplatin-based therapy (P = 0.604 and P = 0.906, respectively). DISCUSSION: These data show that sCRT was associated with less toxicity than cCRT with no associated statistically significant decrease in efficacy outcomes and that sCRT merits further study in this population.

Dual VEGF inhibition with sorafenib and bevacizumab as salvage therapy in metastatic colorectal cancer: results of the phase II North Central Cancer Treatment Group study N054C (Alliance).

BACKGROUND: Bevacizumab (BEV), a monoclonal antibody against vascular endothelial growth factor-A (VEGF-A), is a standard component of medical therapy of metastatic colorectal cancer (mCRC). Activation of alternative angiogenesis pathways has been implicated in resistance to BEV. This phase II study examines the activity of combined vertical blockade of VEGF signaling with sorafenib and BEV as salvage therapy in patients with progressive disease (PD) on all standard therapy in mCRC. METHODS: mCRC patients with documented PD on standard therapy, received sorafenib (200 mg orally twice daily, days 1-5 and 8-12) and BEV (5 mg/kg intravenously, day 1) every 2 weeks. Primary endpoint was 3-month progression-free survival (PFS) rate and secondary endpoints were overall survival (OS), response rate (RR), safety, and feasibility. RESULTS: Of the 83 patients enrolled, 79 were evaluable. Of these, 42 (53%) were progression-free at 3 months. Median PFS was 3.5 months and median OS was 8.3 months. One patient had a partial response and 50 patients (63.3%) had at least one stable tumor assessment. Of 79 evaluable patients, 54 (68%) experienced grade 3/4 adverse events (AEs) at least possibly related to treatment. Most frequent grade 3/4 AEs were: fatigue (24.1%), hypertension (16.5%), elevated lipase (8.9%), hand-foot skin reaction (8.9%), diarrhea (7.6%), and proteinuria (7.6%). Reasons for treatment discontinuation were PD (72%), AEs (18%), patient refusal (8%), physician decision (1%), and death (1%). CONCLUSIONS: The combination of BEV and sorafenib as salvage therapy in heavily pretreated mCRC patients is tolerable and manageable, with evidence of promising activity. CLINICALTRIALSGOV IDENTIFIER: NCT00826540, URL:http://clinicaltrials.gov/ct2/show/NCT00826540.

Allogeneic hematopoietic cell transplantation compared to chemotherapy consolidation in older acute myeloid leukemia (AML) patients 60-75 years in first complete remission (CR1): an alliance (A151509), SWOG, ECOG-ACRIN, and CIBMTR study.

The preferred post-remission therapy for older patients with acute myeloid leukemia (AML) in first complete remission (CR1) remains uncertain. In this retrospective, multicenter study, we compared the outcomes for older AML patients (age 60-77 years) receiving allogeneic hematopoietic cell transplantation (alloHCT) (n = 431) with those treated on prospective National Clinical Trials Network induction and nontransplantation chemotherapy (CT) consolidation trials (n = 211). AlloHCT patients were younger (median age: 64.2 versus 67.9 years, p < 0.001), but more frequently had high-risk AML (high WBC, secondary AML, and unfavorable cytogenetics). Overall survival (OS) was worse in alloHCT during the first 9 months after CR1 (HR = 1.52, p = 0.02), but was significantly better thereafter (HR = 0.53, p < 0.0001) relative to CT. Treatment-related mortality (TRM) following HCT was worse in the first 9 months (HR = 2.8, 95% CI: 1.5-5.2, p = 0.0009), while post-HCT relapse was significantly less frequent beyond 9 months (HR = 0.42, 95% CI: 0.29-0.61, p < 0.0001). Despite higher early TRM, alloHCT recipients had superior long-term OS [29% (24-34%) versus CT 13.8% (9-21%) at 5 years]. Although this is a retrospective analysis with potential biases, it indicates that alloHCT led to heightened early risks from TRM, yet reduced relapse and superior long-term survival relative to CT in older AML patients in CR1.

Older-Patient-Specific Cancer Trials: A Pooled Analysis of 2,277 Patients (A151715).

BACKGROUND: Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older-patient-specific trials, defined as those designed for older patients with cancer, with those enrolled in age-unspecified trials. MATERIALS AND METHODS: We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985-2012. RESULTS: Among 2,277 patients, 1,014 had been enrolled to older-patient-specific and 1,263 to age-unspecified trials. The median age (range) in the older-patient-specific trials was 72 (65-89) years compared with 68 (65-84) years in the cohort of older patients in age-unspecified trials; p < .0001. A greater percentage of patients 75 years or older had enrolled in older-patient-specific trials compared with the cohort of age-unspecified trials: 26% versus 6% (p < .0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9-13.7) and 13.5 years (95% CI, 12.9-14.1) for older-patient-specific and age-unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92-1.28; p = .34; referent: age-unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence-free survival. A lower rate of grade 3-5 adverse events (hematologic and nonhematologic) was reported in older-patient-specific trials (43% vs. 58%; p < .0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results. CONCLUSION: Older-patient-specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers. NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831) IMPLICATIONS FOR PRACTICE: This work underscores the importance of clinical trials that focus on the recruitment of older patients with cancer.

Functional Decline and Resilience in Older Women Receiving Adjuvant Chemotherapy for Breast Cancer.

OBJECTIVES: To analyze self-reported changes in physical function in older women with breast cancer receiving adjuvant chemotherapy. DESIGN: Secondary analysis of the Cancer and Leukemia Group B (CALGB) 49907 prospective randomized clinical trial. SETTING: CALGB institutions in the United States. PARTICIPANTS: Women aged 65 and older with Stage I to III breast cancer enrolled in CALGB 49907 who had physical function data from before and after receipt of adjuvant chemotherapy (N=256; mean age 71.5, range 65-85). MEASUREMENTS: Participants were administered the physical function subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire before chemotherapy, at the end of chemotherapy, and 12 months after chemotherapy initiation. Functional decline was defined as a more than 10-point decrease from baseline at each time point. Resilience was defined as return to within 10 points of baseline. Multivariable regression was used to examine pretreatment characteristics associated with physical function changes. RESULTS: Of 42% of participants who had physical function decline from before to the end of chemotherapy, 47% recovered by 12 months (were resilient). Almost one-third experienced functional decline from before chemotherapy to 12 months later. Pretreatment fatigue was a risk factor for functional decline from before to the end of chemotherapy (P=.02). Risk factors for functional decline at 12 months included pretreatment dyspnea (P=.007) and being unmarried (P=.01). CONCLUSION: Functional decline was common in older women receiving adjuvant chemotherapy for breast cancer in a clinical trial. Although half recovered their physical function, one-third had a clinically meaningful decline at 12 months. Strategies are needed to prevent functional decline in older adults receiving chemotherapy. J Am Geriatr Soc 67:920-927, 2019.

Age and the Risk of Paclitaxel-Induced Neuropathy in Women with Early-Stage Breast Cancer (Alliance A151411): Results from 1,881 Patients from Cancer and Leukemia Group B (CALGB) 40101.

PURPOSE: A few previous studies report a direct relationship between older age and chemotherapy-induced neuropathy. This study further evaluated this adverse event's age-based risk. METHODS: CALGB 40101 investigated adjuvant paclitaxel (80 mg/m2 once per week or 175 mg/m2 every 2 weeks) in patients with breast cancer and served as a platform for the current study that investigated age-based differences in neuropathy. Grade 2 or worse neuropathy, as per Common Terminology Criteria for Adverse Events version 4, was the primary endpoint; patients were assessed at baseline, every 6 months for 2 years, and then annually for 15 years. RESULTS: Among these 1,881 patients, 230 were 65 years of age or older, 556 were 55-64 years, and 1,095 were younger than 55; 1,226 neuropathy events (commonly grade 1 or 2) were reported in 65% of the cohort. The number of grade 2 or worse events was 63 (27%), 155 (28%), and 266 (24%) within respective age groups (p = .14). In univariate analysis, only motor neuropathy had a higher age-based incidence: 19 (8%), 43 (8%), and 60 (5%), respectively (p = .04); in multivariate analyses, this association was no longer statistically significant. Other endpoints, such as time to onset of neuropathy (time from trial enrollment to neuropathy development) and time to improvement (time from maximal grade sensory neuropathy to a one-category improvement), showed no statistically significant age-based differences. In contrast, obesity was associated with neuropathy, and every 2-week paclitaxel was associated with trends toward neuropathy. CONCLUSION: Although paclitaxel-induced neuropathy is common, older age is not an independent risk factor. Clinical trial identification number. NCT00041119 (CALGB 40101). IMPLICATIONS FOR PRACTICE: Age alone is not an independent risk factor for paclitaxel-induced neuropathy.

Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole: a CALGB 40503 (alliance) correlative study.

BACKGROUND: In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer. METHODS: CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade ≥ 3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined. RESULTS: One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade ≥ 3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age ≥ 65 years (p < 0.01), decreased vision (p = 0.04), and poorer pretreatment physical function measures (p < 0.05) were found on univariate analysis to be significantly associated with increased incidence of grade ≥ 3 adverse events. Upon multivariate analysis, age ≥ 65 years (p = 0.01) and decreased vision (p = 0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade ≥ 3 adverse events. CONCLUSIONS: Age (≥ 65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring.

The preference to receive chemotherapy and cancer-related outcomes in older adults with breast cancer CALGB 49907 (Alliance).

OBJECTIVE: Chemotherapy preference refers to a patient's interest in receiving chemotherapy. This study examined whether chemotherapy preference was associated with toxicity, efficacy, quality of life (QoL), and functional outcomes during and after completion of adjuvant chemotherapy in older women with breast cancer. MATERIALS AND METHODS: This study is a secondary analysis of CALGB 49907, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in patients age 65 years or older with breast cancer. A subset of 145 patients completed a questionnaire to describe chemotherapy preference pre-treatment. The association of this pre-treatment preference with the patient's perception of self-health, predicted and actual QoL, patient- and professional-reported toxicity, mental health, self-rated function, and survival was studied during and after treatment. RESULTS: The median age of patients was 71 years and 47% had a high preference for chemotherapy. On baseline demographics, the low preference group had a higher proportion of white patients (95% vs. 78%, p = 0.004). Before treatment, low chemotherapy preference was associated with greater nausea/vomiting (p = 0.008). Mid-treatment, low preference was associated with lower QoL, worse social, emotional and physical function (all p ≤ 0.02) and worse nausea/vomiting, cancer symptoms and financial worries (all p < 0.05). The association noted mid-treatment, resolved after treatment completion except with financial worries which persisted at 24 months. Low preference was associated with higher rates of grade 3-5 adverse events (53% vs. 34%, p = 0.02) but was not associated with survival. CONCLUSIONS: Low chemotherapy preference prior to treatment initiation was associated with lower QoL, worse physical symptoms and self-rated function and more adverse events mid-treatment. There is no association of chemotherapy preference with survival.

Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611).

OBJECTIVE: Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. PATIENTS AND METHODS: We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014. Toxicity was assessed per the NCI-CTCAE (version 3-5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression. RESULTS: 1199 patients (409 age ≥ 65; 790 age < 65) were analyzed; 438 received only biologic therapy (145 age ≥ 65; 293 age < 65), and 761 received biologic + chemotherapy (264 age ≥ 65; 497 age < 65). The odds of grade three or four hematologic [odds ratio (OR) 1.70; p = 0.009: 95% CI (1.57-1.84)] and non-hematologic toxicities [OR 1.47; p = 0.022; 95% CI (1.39-1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p = 0.017; 95% CI (1.64-2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p = 0.006; 95% CI (2.25-4.39) for OS and 3.06; p = 0.011; 95% CI (2.10-4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed. CONCLUSIONS: CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL.

Promoting Accrual of Older Patients with Cancer to Clinical Trials: An Alliance for Clinical Trials in Oncology Member Survey (A171602).

BACKGROUND: There are multiple known individual- and practice-level barriers to enrollment of older patients with cancer to clinical trials, but little is known about how the clinical research workforce feels about potential higher-level strategy changes aimed to promote increased enrollment of older patients. SUBJECTS, MATERIALS, AND METHODS: We invited all 11,351 Alliance for Clinical Trials in Oncology ("Alliance") members to participate in an anonymous, web-based survey to examine awareness of current accrual patterns for older patients to clinical trials, to ascertain consensus on how to tackle enrollment challenges, and to provide the impetus for high-level changes to improve clinical trial accrual of older patients with cancer. RESULTS: During the period from February 28, 2017, to June 16, 2017, 1,146 Alliance members participated (response rate = 10%), including a national diverse sample of physicians, nurses, administrative/clinical research staff, and patient advocates with representation from community, academic, and rural sites. Overall, one third felt that >50% of clinical trial enrollees should be age ≥65, and 64.9% felt the Alliance could improve upon enrollment of older patients. The four most commonly ranked strategies to improve enrollment of older patients were creating more dedicated trials for this population (36.3%), minimizing exclusion criteria focused on comorbidity (35.5%), developing independent strategies for those aged ≥65 and for those aged ≥70 (33.2%), and requiring that most/all Alliance trials have a specific expansion cohort of older patients (30.0%). CONCLUSION: We anticipate that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials. IMPLICATIONS FOR PRACTICE: This survey of the Alliance for Clinical Trials membership sought opinions on potential, large-scale, national strategies to improve accrual of older adults with cancer. Consensus was found around multiple strategies, including creating more dedicated trials for older patients, developing less stringent eligibility criteria, and mandating expansion cohorts of older patients within broader Alliance trials. It is anticipated that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials.

Evaluating the efficacy of vaginal dehydroepiandosterone for vaginal symptoms in postmenopausal cancer survivors: NCCTG N10C1 (Alliance).

BACKGROUND: Women with estrogen deficiencies can suffer from vaginal symptoms that negatively impact sexual health. This study evaluated vaginal dehydroepiandrosterone (DHEA) for alleviation of vaginal symptoms. METHODS: This three-arm randomized, controlled trial evaluated DHEA 3.25 mg and DHEA 6.5 mg, each compared to a plain moisturizer (PM) over 12 weeks, to improve the severity of vaginal dryness or dyspareunia, measured with an ordinal scale, and overall sexual health using the Female Sexual Function Index (FSFI). Postmenopausal women with a history of breast or gynecologic cancer who had completed primary treatment, had no evidence of disease, and reported at least moderate vaginal symptoms were eligible. The mean change from baseline to week 12 in the severity of vaginal dryness or dyspareunia for each DHEA dose was compared to PM and analyzed by two independent t tests using a Bonferroni correction. RESULTS: Four hundred sixty-four women were randomized. All arms reported improvement in either dryness or dyspareunia. Neither DHEA dose was statistically significantly different from PM at 12 weeks (6.25 mg, p = .08; 3.25 mg, p = 0.48), although a significant difference at 8 weeks for 6.5 mg DHEA was observed (p = 0.005). Women on the 6.5 mg arm of DHEA reported significantly better sexual health on the FSFI (p < 0.001). There were no significant differences in provider-graded toxicities and few significant differences in self-reported side effects. CONCLUSION: PM and DHEA improved vaginal symptoms at 12 weeks. However, vaginal DHEA, 6.5 mg, significantly improved sexual health. Vaginal DHEA warrants further investigation in women with a history of cancer.