Citations

PURPOSE In the United States, the National Cancer Institute National Cancer Clinical Trials Network (NCTN) groups have conducted publicly funded oncology research for 50 years. The combined impact of all adult network group trials has never been systematically examined. METHODS We identified randomized, phase III trials from the adult NCTN groups, reported from 1980 onward, with statistically significant findings for ≥ 1 clinical, time-dependent outcomes. In the subset of trials in which the experimental arm improved overall survival, gains in population life-years were estimated by deriving trial-specific hazard functions and hazard ratios to estimate the experimental treatment benefit and then mapping this trial-level benefit onto the US cancer population using registry and life-table data. Scientific impact was based on citation data from Google Scholar. Federal investment costs per life-year gained were estimated. The results were derived through December 31, 2020. RESULTS One hundred sixty-two trials comprised of 108,334 patients were analyzed, representing 29.8% (162/544) of trials conducted. The most common cancers included breast (34), gynecologic (28), and lung (14). The trials were cited 165,336 times (mean, 62.2 citations/trial/year); 87.7% of trials were cited in cancer care guidelines in favor of the recommended treatment. These studies were estimated to have generated 14.2 million (95% CI, 11.5 to 16.5 million) additional life-years to patients with cancer, with projected gains of 24.1 million (95% CI, 19.7 to 28.2 million) life-years by 2030. The federal investment cost per life-year gained through 2020 was $326 in US dollars. CONCLUSION NCTN randomized trials have been widely cited and are routinely included in clinical guidelines. Moreover, their conduct has predicted substantial improvements in overall survival in the United States for patients with oncologic disease, suggesting they have contributed meaningfully to this nation's health. These findings demonstrate the critical role of government-sponsored research in extending the lives of patients with cancer.

6077 Background: E3311 is a phase II randomized study which showed favorable outcomes among intermediate (INT) risk HPV+ OPC patients (pts) who underwent TOS followed by pathology-guided or adapted, deintensified adjuvant treatment. Among HPV+ pts treated with definitive chemoradiation, survival outcomes are worse among those who smoked > 10 pack years (pk-yrs). Methods: We retrospectively analyzed demographics, pathologic results, and efficacy outcomes from E3311 by smoking group (current (C) vs. former (F) and > 10 vs. ≤10 pk-yrs – the latter a pre-specified stratification factor for INT patients). Binary and categorical variables were compared using a chi-square test (or Fisher’s exact test for small sample sizes). Ordinal variables were compared using a Wilcoxon rank sum test. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using a log-rank test. Results: Among 359 evaluable pts, performance status (PS) was significantly worse for pts with > 10 pk-yrs vs. ≤10 pk-yrs (15.4% vs. 7.9% with PS of 1, p = 0.034). Primary site, margin status, histologic grade, stage, and extranodal extension were not significantly different between the groups of > 10 vs. ≤10 pk-yrs. Smoking status (F vs. C) was available for 182 pts with a history of smoking. Slightly more C vs. F smokers had tonsil as primary site (79.5% vs. 65.0%, p = 0.09). Positive margins were significantly more frequent among C smokers (10.3% vs. 2.1%; p = 0.029). Overall, there were no significant differences in PFS (p = 0.55) or OS (p = 0.94), comparing those with > 10 vs. ≤10 pk-yrs, or comparing C vs. F smokers (p = 0.76, p = 0.82, respectively). Similarly, no significant differences were observed within the treatment arms. (Table 1) Conclusions: In this analysis of smoking status in E3311, INT risk HPV+ OPC pts who are C smokers or have a history of > 10 pk-yrs had favorable 3-yr PFS and OS rates that were not significantly worse than those with < 10 pk-yrs history. This data represents the first treatment approach for HPV+ OPC in which outcomes were not influenced by smoking status. Clinical trial information: NCT01898494. [Table: see text]

12094 Background: The Functional Assessment of Cancer Therapy patient-reported outcomes (PRO) item GP5 (“I am bothered by side effects of treatment”) estimates treatment tolerability. We aimed to extend our previous finding that GP5 predicts early aromatase inhibitor (AI) discontinuation (E1Z03, 96% White) in the racially diverse E1Z11 trial cohort. Methods: E1Z11 was coordinated by the ECOG-ACRIN NCI Community Oncology Research Program (NCORP) Research Base. Postmenopausal women initiating anastrozole per clinical care for ER+ stage I-III breast cancer with a pain score 0-3/10 and no rheumatologic comorbidities were eligible. Accrual of a racially diverse cohort of 1,000 women, including Black and Asian women, was planned. GP5 was administered prior to initiating anastrozole (trial baseline) and at 3, 6, 9 and 12 months. GP5 was scored on a 5-point Likert scale from 0 (not at all) to 4 (very much) and dichotomized as no/little treatment bother (0/1) or moderate/high treatment bother (2-4), consistent with previous analyses. A univariate Cox proportional hazards model estimated baseline GP5’s association with treatment duration via hazard ratio (HR). Early treatment discontinuation status was defined as treatment duration < 12 months with discontinuation not attributed to disease progression or death (n = 4), consistent with previous analyses. Results: 1,046 women enrolled from 6/2013-10/2018 (640 White, 201 Black, 205 Asian), including 590 (56%) from NCORP Community or Minority/Underserved Sites. Approximately 10% (100/987 with GP5 data) reported moderate/high treatment bother prior to initiating anastrozole. Anastrozole discontinuation rate at 1-year was 26.2% overall; it was lower among women with no/little treatment bother (25.7%, GP5 = 0-1) compared to moderate/high treatment bother prior to initiating anastrozole (34.7%, GP5 = 2-4; HR = 1.50, 95% confidence interval [CI]:1.04-2.15, p = 0.027). Subgroup analyses by racial cohort showed a similar predictive effect of GP5 in the White (n = 606, HR = 1.76, 95% CI: 1.12-2.77, p = 0.014) and Black (n = 184, HR = 1.85, 95% CI: 0.92-3.71, p = 0.079) cohorts, but not in the Asian cohort (n = 197, HR = 0.40, 95% CI: 0.10-1.62, p = 0.20). Conclusions: Moderate/high treatment bother prior to starting anastrozole was observed in 10% of patients and associated with a higher risk of early discontinuation, except in Asian patients. Our findings support the presence of a treatment tolerability threshold which can be compromised by pre-treatment burden. Treatment tolerability may also be influenced by cultural and genetic factors, which will be explored in further analysis of genetic and PRO data. Clinical trial information: NCT01824836.

6514 Background: Tobacco use is a modifiable risk factor for adverse outcomes among patients diagnosed with cancer. Despite ASCO’s recommendation for assessment and treatment of tobacco use, integration into cancer care is suboptimal. Socioeconomic contexts influence access and utilization of tobacco treatment, but little is known about the relationship between neighborhood socioeconomic disadvantage (NSD) and tobacco assessment, assistance, and cessation among cancer patients enrolled in clinical trials. Methods: The NCI Cancer Patient Tobacco Use Questionnaire (C-TUQ) was centrally administered to participants enrolled in 10 ECOG ACRIN clinical trials (9 therapeutic, 1 imaging). We examined associations of NSD with patient-reported rates of receiving brief tobacco cessation support (i.e., Ask, Assist (counseling)) and cessation (past 30d quit attempts and duration). NSD was measured using the national Area Deprivation Index (ADI) based on participant’s zip code. Associations between ADI (low, intermediate, and high) and tobacco variables were evaluated using logistic regression and ANOVA. Results: 740 patients, completing the C-TUQ between June 2017-October 2021, can be classified as 402 (54%) never smokers, 81 (11%) current smokers, and 257 (35%) former smokers. Patients were 70% male; 94% white; 3% Hispanic; mean age 58.8 (SD 9.0). Cancer diagnoses were 36% leukemia; 19% lymphoma, 18% prostate, 11% breast; 9% melanoma, 7% myeloma, and 0.5% head and neck. Patients were categorized into high (33%), intermediate (34%) and low (33%) disadvantaged neighborhoods. Patients in high (vs. low) disadvantaged neighborhoods were more likely to report being asked about smoking (OR = 3.90; 95% CI (confidence interval), 1.61 to 9.46; p = 0.0062) but less likely to report receiving counseling to help quit smoking (OR = 0.20; 95% CI, 0.06 to 0.73; p = 0.0234). Patients from high disadvantaged neighborhoods had the shortest quit duration, followed by patients from intermediate and low disadvantaged neighborhoods (mean = 145.78, 187.66, and 210.98 months, respectively, p = 0.0372). Conclusions: Greater socioeconomic neighborhood disadvantage was associated with increased assessment of tobacco use but decreased tobacco treatment referral, and the shortest quit duration. More research is needed to promote increased referral to tobacco treatment for individuals with cancer from disadvantaged neighborhoods to promote and sustain cessation.

4020 Background: High grade (G3) GEPNENs are a rare and heterogeneous disease entity for which there is little prospective treatment data. EP chemotherapy is the treatment standard but this may not be appropriate for all G3 GEPNEN pts. CAPTEM has demonstrated activity in G3 GEPNENs and may be a promising alternative. EA2142 aimed to determine if CAPTEM was superior to EP in pts with G3 GEPNENs. Methods: This was a multicenter, randomized (1:1) phase II trial for pts with a locally advanced and unresectable or metastatic well differentiated G3 neuroendocrine tumor (NET) or a poorly differentiated, non-small cell G3 neuroendocrine carcinoma (NEC) of suspected gastrointestinal origin and an ECOG PS of 0-2. Pathology must have demonstrated a Ki-67 of 20-100% or at least 10 mitoses/10 high powered field. Pts were randomized to receive capecitabine 750 mg/m2 orally every 12 hours on days 1-14 and temozolomide 200 mg/m2 orally once daily on days 10-14 of a 28-day treatment cycle (Arm A) or etoposide 100 mg/m2 daily on days 1-3 with either cisplatin 25 mg/m2 daily on days 1-3 or carboplatin AUC 5 on day 1 of a 21-day treatment cycle (Arm B). Restaging scans were performed every 8 weeks and toxicity monitored per CTCAEv4. Final statistical plan was to accrue 80 pts to detect a 67% improvement in progression free survival (PFS) (primary endpoint) with CAPTEM as compared to EP, 80% power and one-sided significance level of 0.10. A planned interim analysis for efficacy and futility was conducted. Results: A total of 67 pts were enrolled (Arm A, n=32; Arm B, n=35). Male 58%, African American 4%, Asian 3%. Mean age 61. Among 63 eligible pts, primary tumor site pancreatic 56%, non-pancreatic 43%. Poorly differentiated 57%, well differentiated 33%, unknown 10%. Mean Ki-67 48% (Arm A), 60% (Arm B). The study was closed prior to full accrual due to futility at 57.7% information time. In the interim analysis, among 62 eligible pts, PFS, overall survival and response rate with CAPTEM were 2.43 months (mos) (95% CI 2.04, 7.72), 12.6 mos, 9% respectively vs 5.36 mos (95% CI 2.14, 7.23), 13.6 mos and 10% with EP. Toxicity was evaluable in 57 pts with Grade (G) 3/4 events occurring in 29% of pts on Arm A, 66% of pts on Arm B. G3/4 events occurring in more than 5% of pts on Arm A—febrile neutropenia (n=2); abdominal pain (n=2); diarrhea (n=2); nausea (n=2); neutropenia (n=2); dehydration (n=2) and on Arm B—anemia (n=8); febrile neutropenia (n=2); fatigue (n=2); lymphopenia (n=2); neutropenia (n=12); thrombocytopenia (n=4); leukopenia (n=6). There was one G5 event on Arm A due to sepsis. Conclusions: CAPTEM does not appear to be superior to EP chemotherapy as front-line treatment for pts with G3 NENs but does demonstrate a more favorable toxicity profile. Studies assessing G3 NET independently of G3 NEC are needed. Clinical trial information: NCT02595424.