Castellino, Sharon M.

AbstractThe goal of therapy in pediatric Hodgkin lymphoma (HL) is to maximize overall survival while minimizing the morbidity of curative therapy. Key findings from recent Children's Oncology Group (COG) trials include: (i) superior event‐free survival with the addition of brentuximab vedotin (Bv) in frontline regimens for high‐risk disease, (ii) successful reduction in myeloablative regimens with demonstrated safety and efficacy of Bv and checkpoint inhibitor therapy in relapsed disease, and (ii) the potential to select a population that can be salvaged after relapse without receiving a stem cell transplant. The COG HL committee will lead a National cancer Institute National Clinical Trials Network phase 3 trial to evaluate the combination of Bv/nivolumab in early‐stage disease. Ongoing advances in technology and blood biomarkers are increasing the ability to deliver biologically driven, personalized treatment for HL.

6539 Background: HER2-enriched breast cancer (estrogen and progesterone receptors negative and HER2-positive) has no worse prognosis than other breast cancers if it is treated with HER2-targeted therapy. Medicaid expansion under the Affordable Care Act (ACA) has been shown to be associated with improved access to care and outcomes for many cancers, but its impact on care for HER2-enriched breast cancer is unknown. To fill this gap, we examined the association of Medicaid expansion with receipt of guideline-concordant treatment, time to treatment, and survival among newly diagnosed nonelderly women with HER2-enriched breast cancer. Methods: Women aged 18-62 years newly diagnosed with HER2-enriched breast cancer between 2010 and 2018 were identified from the National Cancer Database. Our primary outcomes included receipt of stage-based guideline-concordant treatment, initiation of treatment <60 days, and stage-specific 2-year overall survival. A difference-in-differences (DD) approach compared outcome changes following the expansion in Medicaid expansion vs. non-expansion states. A linear probability model estimated treatment outcome, and a flexible parametric survival model evaluated survival. All models were clustered at the state level and adjusted for age group, race/ethnicity, rurality of residence, zip code-level income, comorbidity, and diagnosis year. Results: A total of 31,354 patients with HER2-enriched breast cancer were included, including 19,255 in expansion states and 12,099 in non-expansion states. Compared to patients in expansion states, patients in non-expansion states were more likely to be racial/ethnic minorities, uninsured, and diagnosed at late-stage. Medicaid expansion was not significantly associated with changes in receipt of surgery for stage I-III disease but was associated with an increase of 4.42 percentage points (ppt, 95% CI: 0.09, 8.74) in receipt of chemotherapy/targeted therapy for stage IV disease, with an increase from 90.4% pre-expansion to 92.8% post-expansion in expansion states and a decrease from 93.7% to 91.9% in non-expansion states. Medicaid expansion was also significantly associated with a 2.41 ppt increase in initiating guideline-concordant treatment within 60 days (95% CI: 0.66, 4.17; 83.5% to 82.5% in expansion states vs. 86.6% to 83.7% in non-expansion states), and a 1.18 ppt increase in two-year survival rate (95% CI: 0.03, 2.33; 94.0% to 94.9% in expansion states vs. 94.3% to 94.1% in non-expansion states). The increase in two-year survival associated with Medicaid expansion was most prominent for stage III patients (DD=3.63 ppt; 95% CI: 0.64, 6.62). Conclusions: Medicaid expansion was associated with increased receipt of timely treatment and improved 2-year survival among nonelderly women newly diagnosed with HER2-enriched breast cancer.

1509 Background: Medicaid expansion under the Affordable Care Act has been shown to increase insurance coverage and early-stage cancer diagnoses for young adults (YAs), the age group with the highest uninsured rate. We examined whether Medicaid expansion was associated with increased receipt of timely, guideline-concordant treatment and survival among YA women newly diagnosed with breast cancer, the most common YA cancer diagnosis. Methods: Using the National Cancer Database, we identified 51,675 women aged 18-39 years who were diagnosed with breast cancer in 2011-2018. We applied the difference-in-differences (DD) method to estimate outcome changes pre vs. post Medicaid expansion, in expansion- vs. non-expansion states. Linear probability models estimated associations of Medicaid expansion with receipt of guideline-concordant treatment – including any endocrine therapy among women with ER-positive or PR-positive breast cancer, and any chemotherapy or targeted therapy among women with ER-negative and PR-negative breast cancer – and initiation of guideline-concordant treatment (surgery, chemotherapy, or targeted therapy for stage I-III diagnoses, and systemic therapy for stage IV diagnoses) <60 days after diagnosis. Flexible parametric survival models were used to estimate 2-year overall survival. DD models also adjusted for age, race/ethnicity, rurality, zip code-level income, comorbidity, and diagnosis year, with standard errors clustered at the state level. Analyses were stratified by stage at diagnosis (stage I-III vs. IV). Results: Of the subset of women with stage I-III ER-positive or PR-positive breast cancer, the percentage receiving endocrine therapy increased in expansion states (85.20% pre-expansion to 86.46% post-expansion), but decreased in non-expansion states (84.32% to 82.79%), resulting in a net increase of 2.42 percentage points (ppt; 95% CI = 0.56 to 4.28) associated with Medicaid expansion in the adjusted DD model. Among all women with stage I-III breast cancer, the percentage with treatment initiation <60 days after diagnosis decreased less in expansion states (84.10% pre-expansion to 82.36% post-expansion) than in non-expansion states (86.95% to 83.98%), resulting in a net reduction of 1.61 ppt (95% CI = 0.05 to 3.18) in treatment delays associated with Medicaid expansion. Notably, the 2-year overall survival increased in expansion states (96.84% pre-expansion to 96.99% post-expansion), but decreased in non-expansion states (97.24% to 96.30%), resulting in a net survival increase of 1.00 ppt (95% CI = 0.21 to 1.79) associated with Medicaid expansion. Conclusions: Among YA women with stage I-III breast cancer, Medicaid expansion was associated with increased receipt of guideline-concordant treatment, reduced delays in treatment initiation, and improved 2-year survival.

Abstract Children’s Oncology Group (COG) trial AHOD0431 reduced systemic therapy and used response-adapted involved-field radiotherapy (IFRT) in early-stage pediatric classic Hodgkin lymphoma. We investigated the impact of positron emission tomographic response after 1 cycle (PET1) and on IFRT outcomes and pattern of relapse. Patients in AHOD0431 underwent PET1 response assessment after AVPC (doxorubicin, vincristine, prednisone, and cyclophosphamide). “Rapid early responders” (RERs) had a negative PET1 (PET1−); “slow early responders” (SERs) had a positive PET1 (PET1+). Patients with a partial response by computed tomographic and functional imaging after 3 chemotherapy cycles received 21-Gy IFRT, whereas complete responders had no IFRT. Progression-free survival (PFS) was evaluated for RERs and SERs treated with or without IFRT. Recurrence sites were initial, new, or both. Relapses involving initial sites were characterized as “within the PET1+ site” or “initially involved but outside the PET1+ site.” Median follow-up was 118 months. The 10-year PFS rate among RERs was 96.6% with IFRT and 84.1% without IFRT (P = .10), whereas SERs were 80.9% with IFRT and 64.0% without IFRT (P = .03). Among 90 RERs who did not receive IFRT, all 14 relapses included an initial site. Among 45 SERs receiving no IFRT, 14 of 16 relapses were in the initial site (9 PET1+ site only). Among 58 patients receiving IFRT, 5 of 10 relapses were in the PET1+ site. After 3 cycles of AVPC alone, RERs showed favorable results. Conversely, SERs had unfavorable outcomes with AVPC alone, although they improved with 21-Gy IFRT. RT remains an important component of treatment for SERs. This trial was registered at www.clinicaltrials.gov as #NCT00302003.

7504 Background: The anti-CD30 antibody drug conjugate, Brentuximab vedotin (Bv) is approved for adults with advanced stage HL but its use has not been established in children or adolescents. We compared the efficacy and safety of Bv with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVE-PC) to the standard pediatric dose intensive regimen ABVE-PC, inclusive of bleomycin. Methods: This multicenter randomized, open-label phase 3 study enrolled patients 2-21 years (yrs) with previously untreated HL, stages IIB + bulk, IIIB, IVA, IVB. Patients were randomized to 5 cycles of either ABVE-PC or Bv-AVE-PC given every 21 days with granulocyte colony-stimulating factor support. Centrally reviewed PET-CT after 2 cycles (PET2) identified slow responding lesions (SRL) defined as Deauville score > 3. Involved site radiotherapy (ISRT) was given to bulky mediastinal adenopathy and SRL. The primary objective was 3-year EFS; events include relapse/progression, second malignant neoplasm (SMN) or death. Final data cutoff was 31 December 2021. Results: 600 participants were enrolled across 151 institutions from March 2015 to August 2019; 587 were eligible. Median age was 15.6 yrs (range 3.4-21). Patient and disease characteristics were balanced across study arms. Histology was nodular sclerosing in 76.5%. Stage distribution: 20.6% IIB-bulk; 19.3% IIIB; 28.5% IVA; 31.7% IVB. At a median follow-up of 42.1 mos (0.1-80.9), 3-year EFS (95%CI) by intent-to-treat analyses was 82.5% (77.4, 86.5) with ABVE-PC and 92.1% (88.4, 94.7) with Bv-AVE-PC (HR 0.41 (0.25, 0.67), p = 0.0002). Median time to 1st event was 9.4 months for both arms but the range differs by arm (3.6-57.8 ABVE-PC; 1.3, 25.8 Bv-AVE-PC). Relapse rate was 17% following ABVE-PC and 7% with Bv-AVE-PC. One SMN is noted in each arm: thyroid cancer at 57.8 mos and acute myeloid leukemia at 20.3 mos. 3-year overall survival (95%CI) was 98.5% (96.0, 99.4) for ABVE-PC and 99.3% (97.3, 99.8) for Bv-AVE-PC (p = 0.38). PET2 SRL rates were comparable (ABVE-PC 19% vs. Bv-AVE-PC 18%, p = 0.8). As-treated ISRT receipt did not differ (ABVE-PC 55.7% vs. Bv-AVE-PC 52.7%, p = 0.69). No difference in grade 3/4 adverse events was observed; myelosuppression, reflected in a 32% incidence of > grade 3 febrile neutropenia, did not differ by arm (p = 0.67). Only 19% of patients experienced > grade 2 neuropathy by the Balis pediatric neuropathy scale, with no difference between arms (p = 0.86). Conclusions: Brentuximab vedotin with AVE-PC in a dose intensive regimen has superior efficacy to ABVE-PC for pediatric patients with high-risk HL. A 59% risk reduction in EFS was achieved with no increase in toxicity and with fewer patients receiving ISRT compared to prior pediatric trials for high-risk HL. Clinical trial information: 02166463.