Behrens, Robert J.

3626 Background: For patients (pts) with dMMR stage III colon cancer, the addition of atezolizumab (atezo) to adjuvant 5-fluorouracil, leucovorin plus oxaliplatin (mFOLFOX6) significantly improved disease-free survival in ATOMIC (NCT02912559). Here we present HRQOL data. Methods: Pts with surgically resected stage III dMMR colon cancer were randomized (1:1) to receive mFOLFOX6 + atezo (840 mg IV q2 weeks) for 12 cycles (6 months [mo]) followed by atezo monotherapy for 13 cycles (12 mo total) versus mFOLFOX6 for 12 cycles. HRQOL was an exploratory endpoint measured using the FACT-C (includes FACT-G), FACT/GOG-NTX, EQ5D-5L, and PRO-CTCAE. Optional participation was by paper surveys at trial registration, prior to treatment cycles 4 and 7, and at 6, 12, and 36 mo after registration. Mean changes from baseline (BL) were compared between treatment arms using general linear mixed models (negative mean changes indicate worsening). At 6 mo, a two-sided 95% confidence interval excluding a difference of 1.9 points (FACT/GOG-NTX) and 6 points (FACT-C Trial Outcome Index [TOI]) favoring the mFOLFOX6 arm would indicate non-inferiority of the addition of atezo. Rates of side effect bother (FACT-G item GP5) and pt-reported adverse events (AEs) by PRO-CTCAE (composite scores, baseline adjusted) were compared using Fisher’s exact tests. Results: Of 712 randomized pts, 581 (285 atezo+mFOLFOX6; 296 mFOLFOX6) consented to participate in the survey. Pts completed 2398/3021 (79%) of expected surveys across all time points (1218/1489 [82%] atezo+mFOLFOX6; 1180/1532 [77%] mFOLFOX6). The difference in mean changes from BL between arms indicated non-inferiority of the addition of atezo at 6 mo (table); differences remained small at 12 and 36 mo. No significant differences in mean changes from BL between arms were found at 6, 12, or 36 mo for any scale. At 6 mo, 16% vs 20% of pts in each arm reported at least “quite a bit” of side effect bother (p=0.34), favoring atezo. Across cycles, atezo was associated with higher rates of pt-reported itchy skin (62% vs 48%), cough (53% vs 43%), and shortness of breath (51% vs 41%) [all p<0.05]. Conclusions: Addition of atezo to mFOLFOX6 slightly increases pt-reported AEs, but its effect on HRQOL is minimal and not clinically meaningful. Results support tolerability of atezo+mFOLFOX6 as standard of care adjuvant treatment for pts with dMMR stage III colon cancer. Support: UG1CA189823, U10CA180821, U10CA180882; Genentech, a member of the Roche group; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02912559 . Scale Mo Mean change from BL – atezo+mFOLFOX6 Mean change from BL – mFOLFOX6 Diff (95% CI) FACT/GOG-NTX 6 -10.0 -10.6 0.6 (-0.8, 2.1) 12 -8.0 -9.4 1.4 (-0.2, 2.9) 36 -7.2 -6.9 -0.4 (-2.1, 1.4) FACT-C TOI 6 -4.1 -2.5 -1.6 (-3.7, 0.6) 12 2.1 1.8 0.3 (-1.9, 2.6) 36 0.7 1.8 -1.1 (-3.7, 1.5)

LBA1 Background: Standard adjuvant chemotherapy of stage III colon cancer consists of a fluoropyrimidine plus oxaliplatin. In patients (pts) with stage III colon cancer and deficient mismatch repair (dMMR), the benefit of an immune checkpoint inhibitor combined with adjuvant chemotherapy is unknown. The phase III ATOMIC trial (NCT02912559) was conducted to determine whether atezolizumab (atezo), an anti-PD-L1 antibody, can improve pt outcomes when added to adjuvant 5-fluorouracil, leucovorin plus oxaliplatin (mFOLFOX6) in pts with stage III dMMR tumors. Methods: We conducted an NCI-sponsored, multicenter and randomized phase III trial in pts with surgically resected stage III dMMR colon adenocarcinoma (any T, N 1,2 M 0 ). Pts, age > 12 years (yr), were accrued at NCTN sites and the German AIO. Tumor dMMR was determined by local immunohistochemistry and centrally verified. Pts were randomized 1:1 to mFOLFOX6 plus atezo (840 mg IV q2 weeks) for 12 cycles (6 months)[mo] followed by atezo monotherapy for 13 cycles (12 mo total) versus mFOLFOX6 alone for 12 cycles. Randomization stratification factors were N-stage (N 1 /N 1c vs N 2 ), T-stage (T 1 -T 3 vs T 4 ) and site (proximal vs distal). The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival and adverse event (AE) profile (CTCAE, PRO-CTCAE). Primary efficacy analysis was done in the intent-to-treat population; DFS was compared by arm (stratified log-rank test). Hazard ratio (HR) and 95% confidence interval (CI) were calculated using a stratified Cox model; 3-yr DFS was determined by Kaplan-Meier method. Among 700 pts., 165 DFS events with two interim analyses (50% , 75% of events) yielded 90% power to detect HR 0.6 (3-yr DFS 75% vs. 84.2%) assuming exponential survival and 1-sided alpha (0.025). Results: From 9/2017 to 1/2023, 712 pts were randomized (1 pediatric) to either atezo plus mFOLFOX6 (n= 355; atezo arm) or mFOLFOX6 (n= 357). Median pt age was 64 yr. 55.1% were female. Among tumors, 83.8% were proximal, 46.1% were clinical low risk (T 1-3 N 1 ) and 53.9% high risk (T 4 and/or N 2 ). At the second interim analysis, median pt follow-up was 37.2 mo (interquartile range, 24.2 to 55.5) and 124 DFS events were observed. Three-year DFS was 86.4 % (95% CI, 81.8 to 89.9) in the atezo arm and 76.6 % (95% CI, 71.3 to 81.0) in the mFOLFOX6 arm (HR, 0.50; 95% CI, 0.35 to 0.72). Stratified log-rank p-value was <0.0001, crossing the pre-specified efficacy boundary of 0.009. Efficacy for the atezo arm was consistent across subgroups, including pts >70 yr and low- and high-risk groups. Treatment-related > grade 3 AEs occurred in 71.7 % of pts in the atezo arm vs 62.1 % in the mFOLFOX6 arm. Conclusion: The addition of atezolizumab to mFOLFOX6 significantly improved DFS and should be considered the new adjuvant standard of care for patients with dMMR stage III colon cancer. Support: U10CA180821, U10CA180882, U24CA196171; Genentech, a member of the Roche group; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02912559 .

Objectives To estimate the proportion and correlates of self-reported financial difficulty among patients with multiple myeloma (MM) or chronic lymphocytic leukaemia (CLL). Setting Sixty-six US community and minority oncology practices affiliated with the National Cancer Institute Community Oncology Research Programme (NCORP). Participants A total of 521 patients (=18 years) with MM or CLL consented and 416 responded to a survey (completion rate=79.8%). Respondents had a MM diagnosis (74.0%), an associate degree or higher (53.4%), were White (89.2%), insured (100%) and treated with clinician-administered drugs (68.0%). Study design Observational, theoretical model and protocol-based patient survey administered between May 2019 and June 2020. Primary and secondary outcome measures Financial difficulty was assessed using a single-item measure, the EORTC QLQC30: Has your physical condition or medical treatment caused you financial difficulties in the past year? and using an any-or-none composite measure of 22 items assessing financial difficulty, worries and the use of cost-coping strategies. Multivariable logistic regression models assessed the association of financial difficulty with diagnosis, socioeconomic and treatment characteristics. Results About 16.8% reported experiencing financial difficulty using the single-item measure and 60.3% using the composite measure. Most frequently endorsed items in the composite measure were financial worry about having to pay large medical bills related to cancer and difficulty paying medical bills. Financial difficulty using the single-item measure was associated with having MM vs CLL (adjusted OR (aOR), 0.34; 95% CI, 0.13 to 0.84; p=0.02), having insurance other than Medicare (aOR, 2.53; 95% CI, 1.37 to 4.66; p=0.003), being non-White (aOR, 2.21; 95% CI, 1.04 to 4.72; p=0.04) and having a high school education or below (aOR, 0.36; 95% CI, 0.21 to 0.64; p=0.001). Financial difficulty using the composite measure was associated with having a high school education or below (aOR, 0.62; 95% CI, 0.41 to 0.94; p=0.03). Conclusions US patients with MM and CLL report financial difficulty, especially those with low socio-economic status. Interventions are needed to mitigate patients financial difficulty. Trial registration number NCT03870633 .

6602 Background: Treatment advances have greatly improved survival and quality of life among blood cancer patients, yet significant financial costs are a growing concern. Methods: We conducted an observational, prospective survey in 2019-2020 to estimate the self-reported prevalence of financial difficulty among multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients and identify sociodemographic correlates of financial difficulty. Patients with an MM or CLL diagnosis >/= 18 years of age were recruited from NCI NCORP sites of care. Financial difficulty was measured in a previously validated single question from the EORTC QLQ C30 and a composite measure of five questions from the EORTC QLQ C30. Results: 521 MM and CLL patients were registered to the study, 416 patients were administered all or part of the patient survey, for an overall response rate of 79.8%. 16.8% of respondents reported experiencing financial difficulty in response to the single item question and 58.6% reported experiencing financial difficulty in response to the composite measure. Respondents reporting financial difficulty to both measures had reported household incomes of less than $60,000, identified their highest education levels as a high school diploma or GED, had more than one medical comorbidity and used an expensive oral chemotherapeutic agent to treat their blood cancer. Conclusions: Blood cancer patients treated at NCI NCORP sites are experiencing financial difficulties. Results of this study aim to inform physician, site of care and policy efforts to improve access among cancer patients. Clinical trial information: NCT03870633. [Table: see text]

Abstract Background This North Central Cancer Treatment Group (NCCTG) N064A (Alliance) phase II trial evaluated upfront chemoradiotherapy incorporating the EGFR inhibitor panitumumab, followed by gemcitabine and panitumumab for unresectable, non-metastatic pancreatic cancer. Methods The treatment consisted of fluoropyrimidine and panitumumab given concurrently with radiotherapy followed by gemcitabine and panitumumab for 3 cycles followed by maintenance panitumumab. The primary endpoint was the 12-month overall survival (OS) rate and secondary endpoints included confirmed response rate (RR), OS, progression-free survival (PFS), and adverse events. Enrollment of 50 patients was planned and the study fully accrued. Results Fifty-two patients were enrolled, but only 51 were treated and included in the analysis. The median age of patients was 65 years and 54.9% were women. Twenty-two patients received at least 1 cycle of systemic therapy following radiotherapy, but 29 patients received chemoradiotherapy only without receiving subsequent chemotherapy after completion of chemoradiotherapy. The overall RR was 5.9% (95% CI: 1.2%-16.2%). The 12-month OS rate was 50% (95% CI: 38%-67%) which fell short of the per-protocol goal for success (51.1%). The median PFS was 7.4 months (95% CI: 4.5-8.6) and the median OS was 12.1 months (95% CI 7.9-15.9). Grade 3 or higher adverse events were reported by 88%. Conclusion The combination of panitumumab, chemotherapy, and external beam radiation therapy was associated with very high rates of grades 3-4 toxicities and survival results did not meet the trial’s goal for success. This regimen is not recommended for further study (ClinicalTrials.gov Identifier NCT00601627).

8031 Background: New orally administered anticancer treatments have launched in recent years, promising gains in survival and quality of life, but with high prices.Financial difficulties encountered over the course of cancer diagnosis and treatment is a growing concern. These difficulties include inability to pay for basic necessities, presence of medical debt, and high out of pocket burdens relative to income. The primary objective of this study was to estimate the proportion of patients with multiple myeloma (MM) who experience financial difficulties in the past 12 months.Methods: Data collection entailed a comprehensive, theoretically grounded telephone survey and companion medical chart abstraction. Subjects included individuals with a current diagnosis of MM whose current or recent treatment included pharmaceutical-based care and who were not enrolled in a treatment-based trial. Practices eligible to recruit respondents included 44 NCORP affiliates of the Alliance. 14 geographically diverse NCORP affiliates participated between 11/2019 and 6/2020. The primary endpoint of the study was the proportion of subjects who reported financial difficulty in the past 12 months, as measured by the EORTC QLQ-C30 item #28. This proportion and 95% Wilson score confidence interval were estimated for all MM patients who responded to the financial difficulty question ((# reported financial difficulty)/(total # in that category who answered the question)). NCI Central IRB approved this study. Results: 393 subjects were recruited. 304 subjects completed the survey (77.4% response rate). Mean age was 67.5 years (SD 9.8), 143 (46.4%) were female, 24 (7.8%) self-reported race as ‘Black or African American’, 82 (26.6%) reported insured by government insurance Medicare only, 116 (38.2%) reported highest education as high school or below, and 94 (30.5%) reported high income. Mean time from diagnosis to survey enrollment was 3.6 years (SD 4.5). 292 (95.1%) were currently receiving treatment and 192 (62.5%) reported currently receiving a pre-defined ‘expensive’ oral pharmaceutical-based cancer treatment. 20.2% (95% CI:16.1%, 25.0%) reported financial difficulties. Conclusions: This is the first national study to systematically assess the prevalence of financial difficulties and its correlates among MM patients. Approximately 1 in 5 surveyed patients reported financial difficulties. Results of this study aim to inform efforts to improve financial navigation and resources for cancer patients.

4026 Background: Patients (pts) with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma commonly receive neoadjuvant chemoradiotherapy (chemo-RT). Despite this approach the rate of recurrence remains high. Given the difficulties of postoperative therapy, the efficacy of extended neoadjuvant therapy was assessed. Methods: Eligibility criteria included T3-4,N0 – Tany,N(+) disease amenable to radiation and surgery. Pts were randomized to either arm A (docetaxel 60 mg/m2 day 1 , oxaliplatin [Oxal] 85 mg/m2 day 1, and capecitabine 1250 mg/m2/day days 1-14 x 2 cycles [DOC] followed by 5-FU 180 mg/m2/day continuous IV through radiation + Oxal 85 mg/m2 days 1,15,29 + 50.4 Gy radiation (chemo-RT)) or arm B (chemo-RT alone). Randomization was stratified by ECOG PS (0/1 vs 2) and stage (II vs III/IVA). Primary endpoint was pathologic complete response (PCR) rate, defined as no gross or microscopic tumor identified in the surgical specimen. Interim analysis assessed efficacy and futility of the experimental intervention. Wilcoxon rank sum and Fisher’s exact tests were used to compare clinical/pathologic factors between arms. Results: Baseline and stratification factors were well balanced between arms. Of 42 pts included in the interim analysis (86% male; age [median 63, range 38-88], 100% PS 0/1; 71% stage III; 55% esophagus, 40% GEJ; 36% measurable disease), 4 and 1 pts in arms A and B, respectively, did not have surgery due to death (A, 2), progressive disease (A, 1), alternative treatment (A, 1) or adverse event (B, 1). Among 21 arm A pts, 21, 20, and 19 pts started 1st cycle of DOC, 2nd cycle of DOC and chemo-RT, respectively. All arm B pts received chemo-RT. 33% (7/21) of arm A and 48% (10/21) of arm B pts achieved PCR (p=0.53). Among pts undergoing surgery, 94% (16/17) and 100% (20/20) of arm A and B pts had complete resection (p=0.46). 38% and 24% of arm A and B pts experienced at least one grade 4+ adverse event at least possibly related to treatment (p=0.51). Conclusions: Extended neoadjuvant therapy in pts with locally advanced esophageal or GEJ adenocarcinoma failed to improve the PCR rate. Follow-up in regard to survival and rate of recurrence is ongoing. Clinical trial information: NCT00938470.

3640 Background: Prior economic analysis of a 12-gene assay (Oncotype DX), compared with patterns of care reported in the NCCN database of patients with stage II, T3, DNA mismatch repair proficient (MMR-P) colon cancer, predicted that the assay would save medical costs and improve patient well-being (Hornberger et al. Value Health 2012). This study assessed the validity of those findings with actual adjuvant chemotherapy (aCT) recommendations. Methods: Outcomes and costs were estimated for patients with stage II, T3, MMR-P colon cancer using a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium collected data on aCT recommended before and after knowledge of the 12-gene assay results (Srivastava et al. abstract). Quality-adjusted life years (QALY) and medical resource use after recurrence were computed using guideline-validated state-transition probability estimation methods. Risk of progression and incidence of adverse events with different aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2012 Medicare fee schedules. One-way sensitivity analyses were conducted to evaluate parameter influence on economic impact. Results: After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22% (95% CI 11%-32%; McNemar test p<0.001) from 73 (52%) to 42 (30%) patients. Oxaliplatin aCT and 5-FU monotherapy recommendations each declined 11%. Average aCT costs decreased $3,228 for drugs, $750 for administration, and $3,168 for adverse events management. Overall, average total direct medical costs decreased $1,683. The net effect on average patient well-being was a gain of 0.102 QALYs. Total change in medical costs is most influenced by the cost of death due to colon cancer, time-preference discount rate, and the change in aCT recommendations. Savings are expected to persist even if the cost of oxaliplatin dropped by >75% due to generic substitution. Conclusions: The 12-gene assayhas been shown to alter aCT recommendations for patients with stage II, T3, MMR-P colon cancer. This study provides real-world confirmation that these aCT changes reduce direct medical costs and improve patient well-being.

e15169 Background: In metastatic colorectal cancer with deficient DNA mismatch repair (dMMR), anti-PD-1 antibody monotherapy produced high tumor response rates and extended progression-free survival compared to lack of benefit for cancers with proficient MMR. In an ongoing phase III randomized trial, we will determine if the addition of the anti-PD-L1 antibody, atezolizumab (Genentech), to adjuvant FOLFOX can improve patient disease-free survival (DFS) vs FOLFOX alone in patients with stage III colon cancers with dMMR. By blocking the PD-1/PD-L1 interaction, atezolizumab may activate T cells, thereby, restoring their ability to detect and attack tumor cells. Limited data suggest that FOLFOX may increase intratumoral cytotoxic CD8+ T cells that could serve as ‘immune priming'. Methods: Patients with curatively resected stage III colon carcinomas with evidence of dMMR are randomized to modified FOLFOX6 for 6 months (12 cycles) alone (control arm) or combined with atezolizumab (840 mg IV q2 wk) with continuation of the antibody as monotherapy for an additional 6 months (total duration of 12 months) [experimental arm]. Patients will be stratified by T, N stage and tumor sidedness. Local testing for MMR proteins is allowed. Atezolizumab must begin by/with cycle 2. One cycle of FOLFOX is allowed pre-registration. The targeted accrual goal of 700 patients and 165 disease-free survival (DFS) events will provide 90% power to detect an effect size expressed as hazard ratio of 0.6 for the primary endpoint of DFS at two-sided alpha of 0.05. Interim analyses are planned at 50% and 75% of events. Secondary endpoints include overall survival, treatment tolerability, and quality of life. Results: This study is being conducted by the Alliance for Clinical Trials in Oncology, was approved by NCI CTEP and activated in 09/2017. The study is actively accruing and, as of 02/11/2019, 152 patients are enrolled. We are actively exploring an international collaboration. Conclusions: This is a current clinical trial in progress. Clinical trial information: NCT02912559.