Kour, Oudom

31 Background: Incidence of early-onset colorectal cancer (eoCRC, <50 years of age at diagnosis) is increasing globally. However, little is known regarding symptom burden in this sub-population. We compared symptoms in patients with eoCRC to those of patients with average-onset CRC (aoCRC, diagnosed at age ≥ 50). Methods: E2C2 is a stepped-wedge, cluster-randomized pragmatic trial evaluating a collaborative care model for the assessment and management of six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, emotional Distress, and Energy deficit (SPPADE)]. Patients were asked to complete assessments rating each of these symptoms on an 11-point numerical rating scale. Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of patients with CRC, comparing SPPADE symptoms on an initial survey, regardless of timing in treatment course, between patients with eoCRC and aoCRC. Results: Patients with CRC (n=4281) completed a survey between March 2019 and December 2022. Patient demographics and SPPADE symptoms are reported in the table. Patients with eoCRC were more likely to report severe sleep disturbance ( p<0.0001), pain ( p=0.03485), anxiety ( p<0.0001), emotional distress ( p<0.0001), and fatigue ( p=0.01083). In patients with eoCRC, women were more likely to report severe pain (12.6% vs 6.9%, p=0.0069), anxiety (16.1% vs 10.0%, p=0.012), emotional distress (12.1% vs 5.4%, p=0.00066), fatigue (18.9% vs 13.4%, p=0.038), and physical function impairment (10.1% vs 5.8%, p=0.026) compared to men. Conclusions: Patients with eoCRC reported higher symptom severity than patients with aoCRC. This suggests unique needs for symptom management in patients with eoCRC. Additional research is needed to evaluate how time since diagnosis, disease characteristics, cancer-directed treatment patterns, and co-occurring symptoms are associated with specific symptoms in this population. [Table: see text]

7006 Background: Older adult patients (pts) with Philadelphia-chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) have poor survival with chemotherapy. The α-CD22 Ab-drug conjugate inotuzumab ozogamicin (InO) and α-CD19/CD3 T-cell engager blinatumomab (blina) were each superior to chemotherapy in Phase III studies in relapsed/refractory B-ALL. Because InO induces high CR rates and blina can induce durable remissions in low burden disease, we conducted a Phase II trial of induction InO then blina for older adults with newly-diagnosed (ND), Ph-, B-ALL. Methods: Eligible were pts ≥60 years old with ND, Ph-, CD22+ (≥20% of blasts) B-ALL without plan for allogeneic HCT (alloHCT). Pts with CNS leukemia or liver disease were excluded. Induction IA was InO 0.8 mg/m 2 day (d) 1, 0.5 mg/m 2 d8, d15 IV on a 21d cycle. Pts with adequate cytoreduction (marrow blasts by ≥50% or cellularity ≤20%) after IA went to IB if in CR/CRi (InO 0.5 mg/m 2 d1, d8, d15 IV; 28d cycle) or IC if no CR/CRi (InO 0.8 mg/m 2 on d1 and 0.5 mg/m 2 on d8 and d15 IV; 28d cycle). Those without cytoreduction to IA started course II blina. Pts without events in IA/B/C received course II blina CIV (9 mcg/d x 7d then 28 mcg/d x 21d; 14d break; 28 mcg/d x28d). Pts with CR/CRi to InO received 2 more 28d cycles of blina, others received 3 more. CNS prophylaxis was methotrexate 15 mg intrathecal x 8. The primary endpoint was 1-yr event-free survival (EFS) with a lower limit of a 90% CI for 1-yr EFS >10% defined as success. EFS was the time from therapy start to failure to achieve CR/CRh/CRi by end Course II, progression, relapse, or death, whichever occurred first. Results: Thirty-three eligible pts were treated (1 ineligible, 2 nd malignancy). The median age was 71 years (range 60-84). Median WBC count was 3,200/mcl (range 6-38,000). Median CD22 expression was 92% (range 21-100%). Eight pts had therapy-related ALL. The cumulative CR rates through Course IA/B/C and Course II were 85% and 97%, respectively (Table). With median follow up of 22 mo, the 1-yr EFS was 75% (95% CI 61-92%). The 2-sided 90% CI was 63-89% for 1-yr EFS with lower bound above 10% indicating regimen success. Twelve pts had events: 9 relapses, 2 deaths in remission (1 after alloHCT), and 1 death without remission from respiratory failure with sinusoidal occlusion syndrome of liver. The 1-yr OS was 84% (95% CI 72-98%). Nine pts have died, 6 after relapse. Conclusions: InO induction then blina consolidation is highly active for ND, Ph-, CD22+ B-ALL. The regimen is an option for older adults and a comparator regimen for future studies. Support: U10CA180821, U10CA180882, U10CA180820 https://acknowledgments.alliancefound.org . Clinical trial information: NCT03739814 . N=33 I A/B/C II Composite CR* 28 ( 85%) 32 ( 97%) CR 15 (45%) 19 (58%) CRh 11 (33%) 12 (36%) CRi 2 (6%) 1 (3%) Refractory 3 (9%) † - 1-yr EFS 75% (95% CI 61-92%) 1-yr OS 84% (95% CI 72-92%) *CR+CRh+CRi † 1 completed IA only

ImportanceApproval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has generated controversy. Exploratory analyses from individual trials indicate a lack of meaningful benefit from ICI in patients with absent or low PD-L1 expression; however, analysis of a single variable while ignoring others may not consider the instability inherent in exploratory analyses.ObjectiveTo systematically examine the predictive value of tissue-based PD-L1 status compared with that of other variables for ICI benefit in aGEC to assess its stability.Data SourcesMEDLINE, Embase, Scopus, Web of Science, Cochrane Central Register (2000-2022).Study Selection, Data Extraction, and SynthesisRandomized clinical trials (RCTs) were included of adults with aGEC (adenocarcinoma [AC] or squamous cell carcinoma [SCC]) randomized to anti−PD-1 or PD-L1−containing treatment vs standard of care (SOC). Study screening, data abstraction, and bias assessment were completed independently by 2 reviewers. Of 5752 records screened, 26 were assessed for eligibility; 17 trials were included in the analysis.Main Outcomes and MeasuresThe prespecified primary end point was overall survival. The mean hazard ratio (HR) for ICI vs SOC was calculated (random-effects model). Predictive values were quantified by calculating the ratio of mean HRs between 2 levels of each variable.ResultsIn all, 17 RCTs (9 first line, 8 after first line) at low risk of bias and 14 predictive variables were included, totaling 11 166 participants (5067 with SCC, 6099 with ACC; 77.6% were male and 22.4% were female; 59.5% of patients were younger than 65 years, 40.5% were 65 years or older). Among patients with SCCs, PD-L1 tumor proportion score (TPS) was the strongest predictor of ICI benefit (HR, 0.60 [95% CI, 0.53-0.68] for high TPS; and HR, 0.84 [95% CI, 0.75-0.95] for low TPS), yielding a predictive value of 41.0% favoring high TPS (vs ≤16.0% for other variables). Among patients with AC, PD-L1 combined positive score (CPS) was the strongest predictor (after microsatellite instability high status) of ICI benefit (HR, 0.73 [95% CI, 0.66-0.81] for high CPS; and HR, 0.95 [95% CI, 0.84-1.07] for low CPS), yielding a predictive value of 29.4% favoring CPS-high (vs ≤12.9% for other variables). Head-to-head analyses of trials containing both levels of a variable and/or having similar design generally yielded consistent results.Conclusions and RelevanceTissue-based PD-L1 expression, more than any variable other than microsatellite instability-high, identified varying degrees of benefit from ICI-containing therapy vs SOC among patients with aGEC in 17 RCTs.

344 Background: ICI with anti-PD-1 therapy was approved by the US FDA as 1st/2nd-line treatment of advanced GEC regardless of PD-L1 status. It is argued that patients (pts) with PD-L1-low GEC do not benefit from ICI. To avoid spurious exclusion of pts, we systematically reviewed phase 3 trials to assess the magnitude and consistency of PD-L1 to predict benefit from ICI. We also examined other potential predictive factors to understand their magnitude and consistency in comparison with PD-L1 status. Methods: MEDLINE, Embase, Scopus, Web of Science, and Cochrane Central Register were searched for all randomized clinical trials (RCT; 2000-2021) in advanced GEC comparing ICI, alone or with chemotherapy, vs standard of care (SOC). The primary endpoint was overall survival (OS). Study screening, data abstraction, and bias assessment were done independently by two reviewers per PRISMA guidelines. The mean HR for ICI vs SOC was calculated by random effects model. The predictive value of a factor was quantified using relative magnitude and consistency (table). Results: 14 RCTs at low risk of bias were included (N = 9,210 pts; KN62, CM649, CM648, ESCORT1st, KN590, ATT4, JAV100, KN181, KN61, ATT3, ESCORT, RATIONALE302, JAV300, ATT2). 6 trials were 1st-line, 8 were after 1st-line. Treatment comparisons were ICI + chemo vs chemo (6 trials), ICI vs chemo (9 trials), and ICI vs placebo (1 trial). ICI was always anti-PD-1/-L1 (1 trial also had anti-CTLA-4). Table shows primary results. To enable head to head comparisons, subgroup analyses of trials containing both levels of a factor or having similar design were done and generally yielded consistent results. Conclusions: PD-L1 CPS is the strongest predictive biomarker, after MSI, for OS benefit from ICI-containing therapy vs SOC. Additional research on gender is warranted.[Table: see text]