Resected Stage Research Articles

Understanding quality of life issues in patients with advanced melanoma: Phase 1 and 2 in the development of the EORTC advanced melanoma module

AimsWe aimed to develop a European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) module tailored for patients with advanced (resectable or unresectable stage III/IV) melanoma receiving immune checkpoint inhibitors or targeted therapy. MethodsFollowing the EORTC QoL Group module development guidelines, we conducted phases 1 and 2 of the development process. In phase 1, we generated a list of health-related (HR)QoL issues through a systematic literature review and semi-structured interviews with healthcare professionals (HCPs) and patients with advanced melanoma. In phase 2, these issues were converted into questionnaire items to create the preliminary module. ResultsPhase 1: we retrieved 8006 articles for the literature review, of which 35 were deemed relevant, resulting in 84 HRQoL issues being extracted to create the initial issue list. Semi-structured interviews with 18 HCPs and 28 patients with advanced melanoma resulted in 28 issues being added to the initial issue list. Following EORTC module development criteria, 26 issues were removed, and two issues were added after review by patient advocates.Phase 2: To ensure uniformity and avoid duplication, 16 issues were consolidated into eight items. Additionally, an independent expert contributed one new item, resulting in a preliminary module comprising 80 HRQoL items. ConclusionWe identified a range of HRQoL issues (dry skin, xerostomia, and arthralgia) relevant to patients with stage III/IV melanoma. Future module development phases will refine the questionnaire. Once completed, this module will enable standardized assessment of HRQoL in patients with (locally) advanced melanoma.

Whole transcriptome analysis to reveal epithelial-mesenchymal transition after neoadjuvant therapy with or without additional anti-EGFR treatment: Subgroup analysis of esophageal squamous cell carcinomas of the SAKK 75/08 and the EORTC AIO POWER study.

4071 Background: In localized disease of esophageal squamous cell cancer (ESCC), a trend in higher pathological response rates and longer time to treatment failure was seen by addition of anti-EGFR treatment to radio-chemotherapy (RCTX) compared to RCTX alone (SAKK 75/08 trial and others). On the contrary, the effect of anti-EGFR treatment to chemotherapy (CTX) remains unclear as no survival benefit was detected within advanced patients (EORTC-AIO-POWER study). Since perfect discrimination and selection of subgroups with highest benefit for anti-EGFR treatment (AB) is missing, we investigated the predictive values of whole transcriptomic gene expression analysis (WTGE) applied on biopsy tissue. Methods: 50 pretherapeutic formalin fixed paraffin embedded specimens of ESCC patients from SAKK 75/08 study were analyzed for the effect of RCTX with and without anti-EGFR AB. As well as 26 historic controls of primary resected tumor stage equally distributed ESCC were analyzed. For the advanced setting, we analyzed 28 additional pretherapeutic biopsies and compared groups from CTX to CTX plus AB. The HTG EdgeSeq method was used for NGS-based WTGE. Response to treatment was assessed by histopathological tumor regression in localized disease and clinical courses. Response to treatment in the advanced tumor setting was assessed to the clinical course of stable disease and partial response versus non-responders. Results: Firstly, NGS-based WTGE failed to show significant differences in expression patterns between responding and non-responding ESCC patients, irrespective of treatment protocols and EGFR AB in the localized as well in advanced disease setting. Secondly however, comparison between pre-treatment biopsies and posttreatment residual tumor tissues detected 781 genes that were upregulated and 623 that were downregulated with gene sets associated with muscle processes and epithelial-mesenchymal transition (EMT) in the localized disease. EMT genes were also enriched in residual tumors after neoadjuvant RCTX compared to primary resection in an independent control cohort. Additionally performed immunohistochemical studies showed lower numbers of ZEB-1 positive ESCC in an independent collection of tumors treated by neoadjuvant RCTX compared to primary resection. Conclusions: Our Whole transcriptomic gene expression analyses suggest that EMT is involved in responses to neoadjuvant protocols including EGFR targeting therapies. Targeting EMT may be a molecular pathway to increase complete responses after neoadjuvant RCTX in ESCC.

Long-term follow up of E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group.

6009 Background: E3311 is a phase II trial of TOS by credentialed surgeons with pathology-driven deintensified post-operative management in HPV+ OPC. Intermediate risk patients were randomized between standard and reduced dose radiation. We present mature outcome data, at median follow up of 52.4 months (m). Methods: Patients were eligible who had resectable cT1-2 stage III/IV AJCC7 p16+ OPC without matted neck nodes. Those with clear margins, 0-1 + nodes (LN), and no extranodal extension (ENE) were observed (Arm A, N=38); those with clear margins, 2-4 + LN, or ENE ≤1mm were randomized to 50Gy (Arm B, N=100) or 60Gy (Arm C, N=108); those with involved margins, >4 + LN, or >1mm ENE received weekly cisplatin 40 mg/m2 and 60-66Gy (Arm D, N=113). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using a log-rank test, stratified by arm for comparisons of primary site and smoking history. Results: Among 359 evaluable patients, 54-m PFS and OS were 90.6% (90% CI: 87.2%, 93.1%) and 95.3% (90% CI: 93.0%, 96.9%). 54-m PFS by arm was: A 93.2% (90% CI: 79.6%, 97.8%); B 94.9% (90% CI: 89.7%, 97.5%); C 90.2% (90% CI: 82.7%, 94.6%) and D 85.5% (90% CI: 77.5%, 90.8%). 54-m OS by arm was: A 97.1% (90% CI: 85.7%, 99.4%); B 97.9% (90% CI: 93.5%, 99.3%), C 95.1% (90% CI: 90.1%, 97.6%) and D 92.5% (90% CI: 86.9%, 95.7%). Among patients in Arm A, 11 had N0 and 27 N1 stage. Median Arm A lymph node yield (LNY) was 29 (11 to 91 LN) and did not differ for patients with/without recurrence (p=0.83). All Arm A recurrences were in N1 patients: 1 at 18 m and 3 at > 40 m. No significant difference in PFS or OS was observed by prescribed radiation dose for intermediate risk patients (Arm B vs. C). Outcome did not differ by primary site of tonsil vs. other OPC (oOPC): 54-m PFS Tonsil 89.3% (90% CI: 84.9%, 92.5%) vs. oOPC 92.9% (90% CI: 87.0%, 96.2%), p=0.28, and 54-m OS Tonsil 94.6% (90% CI: 91.5%, 96.6%) vs oOPC 96.6% (90% CI: 92.4%, 98.5%), p=0.35. Smoking history also did not impact outcome. 54-m PFS was 89.9% (90% CI: 85.9%, 92.9%) for those with ≤10 pack-years (PY) tobacco exposure and 91.7% (90% CI: 83.9%, 95.9%) for those with >10 PY. Conclusions: TOS, neck dissection with deintensified risk-based post-operative management results in outstanding 54-m PFS and OS across all subsites of T1-2 p16+ OPC, irrespective of smoking history. Late recurrence is not increased when post-operative radiation is reduced from 60 to 50Gy for intermediate risk patients. Pathologic >1mm ENE (N=87), involved margin (N=12) or >4 involved LN (N=30) accurately identify patients at increased recurrence risk and outcomes were favorable among such patients. Among patients with favorable pathologic characteristics, a subset with N1 disease are at risk for late recurrence and further characterization of these patients is warranted. Clinical trial information: NCT01898494 .

Assessing quality of care in early stage resected stage non-small cell lung cancer (NSCLC): An evaluation of epidermal growth factor receptor (EGFR) testing and adjuvant (adj) therapy (tx).

8072 Background: In December 2020, the FDA approved the use of osimertinib in the treatment of stage IB-IIIA (ES) NSCLC patients (pts) with EGFR exon 19 deletions and exon 21 L858R mutations (EGRFm) following tumor resection. Using real-world data, we sought to understand EGFR testing rates among ES pts and whether pts received osimertinib in the adjuvant setting based on EGFRm. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care. From this database, we identified Stage IB – IIIA pts evaluated via medical chart curation who underwent lung cancer resection (R) between 12/1/2021 to 7/31/2023 (N = 803). We assessed adj treatment by stage, EGFR testing rates overall and by stage, EGFR testing rates by adjuvant treatment and non-adj treatment pts, timing of EGFR testing, and treatment rates with an EGFR TKI among EGFRm pts. Descriptive analyses were used and proportions were compared using a chi-squared test. Results: The mean age of the 803 ES R pts in the sample was 69 (SD = 8.3), 53.3% of the pts were female, , and 12% never smoked. We found adj treatment rates among ES R pts to be 56%; these were highest among stage IIIA (N = 245) pts at 70.2%, compared to stage IIB (N = 241) at 68.8%, stage IIA (N = 69) at 53.6% and stage IB (N = 240) at 31.7% (p < 0.001). Among ES R pts, 70% (N = 563) were tested for EGFR; this rate was 78% (N = 455) among ES pts who were R and received adj treatment, compared to 59% (N = 348) among ES R pts who did not receive adj treatment (p < 0.001). EGFR testing rates were highest among stage IIB pts at 76%, compared to stage IIIA pts at 73%, stage IIA pts at 72%, and stage IB pts at 60% (p < .001). Among ES pts who were R and tested for EGFR (N = 563), 14% were tested before surgery, 38% were tested after surgery but before adj treatment, and 48% were tested after initiating adjuvant therapy. EGFRm was found in 10.4% of EGFR tested pts. Among EGFRm ES R pts (N = 59), 54% were treated with an EGFR TKI. EGFRm ES R pts treated with an adj EGFR TKI were highest among stage IIB pts (N = 14) at 93%, compared to stage IIA pts (N = 5) at 60%, stage IB pts (N = 20) at 45%, and stage IIIA pts (N = 20) at 35% (p < 0.01). However, only 69% (N = 41) of EGFRm ES R pts received adj treatment (either chemotherapy or EGFR TKI) and among those pts, 78% (N = 32) received an EGFR TKI. Conclusions: Based on our findings using real-world data for EGFR testing and adjuvant osimertinib use, and in light of the published results from the ADAURA trial which showed disease free survival benefit (HR 0.2) and overall survival benefit (HR 0.49) of adjuvant osimertinib in ES NSCLC, we have identified an opportunity to improve patient outcomes following resection of ES NSCLC by increasing EGFR testing and encouraging treatment with EGFR TKI in exon 19 deletion or exon 21 L858R mutated pts.

Real-world outcomes in patients with biomarker-selected early-stage non-small cell lung cancer.

11156 Background: Extensive literature has assessed the prognostic value of Lung driver mutations (LDMs) in advanced non-small cell lung cancer (aNSCLC). However, their role in predicting outcomes in early-stage cases (eNSCLC) is less defined due to limited data on biomarker-selected eNSCLC. Study variations have led to diverse findings on the prognostic value of individual LDMs in eNSCLC. Methods: We retrospectively analyzed patients with resected stage I-IIIa NSCLC diagnosed between 2011-2023 using the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine lung clinico-genomic database, which consolidates data from approximately 280 US cancer clinics (~800 sites of care). We allocated patients to five cohorts classified by early-stage LDM status: ALK+, EGFR+, KRAS G12C+, KRAS non-G12C+ and wild-type (WT - negative for the listed biomarkers). The clinical attributes and treatment patterns for this cohort were described by our group in a previous abstract; here we analyze recurrence-free and overall survival (RFS and OS) by cohort, using the Kaplan-Meier method. We used Cox regression for multivariate analysis, controlling for demographic and clinical characteristics including age, race, insurance status, stage, histology, and smoking status. Results: The sample contained 1,595 stage I-IIIa patients with known LDM status. Of these, 2.8%, 20.4%, 10.7%, 19.3%, and 46.8% were ALK+, EGFR+, KRAS G12C+, KRAS non-G12C+, and WT. Median OS and RFS were shorter in the WT group compared to any LDM group; results can be found in the table. These differences in OS and RFS persisted in multivariate analysis; hazard ratios (HR) were all statistically significant (p<0.05) and can be found in the table below. Conclusions: In this real-world analysis, patients with eNSCLC LDM-positive tumors had improved OS and RFS relative to WT patients. Differences in OS between WT and LDM+ patients are likely due to frequent receipt of targeted therapy (TT) following progression to advanced disease. However, the small fraction of patients that received adjuvant TT within 6 months of surgery (described in our previous abstract) is not likely to explain observed differences in RFS; thus the differences may be due to innate characteristics of these LDMs. [Table: see text]

Contemporary management of patients with advanced melanoma: Utility of an online interactive decision support tool to assess concordance of healthcare professional treatment patterns with expert recommendations.

e13548 Background: The treatment landscape for patients with melanoma continues to evolve with approvals of novel therapeutic agents for advanced disease and new indications for therapy in earlier-stage disease. Using an online decision support tool, we compared practice patterns and treatment recommendations between community healthcare professionals (HCPs) and key opinion leaders (KOLs). Methods: The online decision support tool was developed with input from 5 KOLs who provided treatment recommendations for 151 hypothetical patients. Case scenarios covered a spectrum of stages (III, IV), central nervous system (CNS) metastases, BRAF mutation status, and treatment histories. HCPs entered specific patient criteria into the tool to define a case and their intended therapy choice and the tool then showed 5 KOL recommendations for that patient case. An analysis of KOL recommendations and HCP-selected therapy was performed. Results: Between August 2023 and January 2024, 156 patient cases were entered by 100 HCPs. HCP and KOL recommendations were concordant in 51% (80/156) of cases. The highest level of discord among HCPs and KOLs was 72% for patients with completely resected stage IIIA melanoma and no positive lymph nodes having a metastatic focus ≥1mm (n = 25) (Table). A lower level of discordance (31%, n = 35) was observed in therapy selection for patients with stage IIIA melanoma and ≥1 positive lymph node. For first-line therapy in patients with unresectable stage III or IV BRAF wild-type melanoma (n = 16), discordance was 50% between HCPs and KOLs. The level of discordance was higher for first-line therapy for patients with BRAF-mutant melanoma (68%, n = 19). For the management of patients with CNS metastases, 40% of HCP therapy selections were not aligned with KOLs (n = 40). More than one half (56%) of HCPs noted that the tool confirmed their treatment plan, and 21% intend to change practice to align with KOLs. Conclusions: This analysis identified areas of discordance in clinical practice between HCPs and KOLs for advanced melanoma that can guide further education and enhance communication of evolving evidence to HCPs. Our data suggest that use of the decision tool can confirm best practices with KOL recommendations and improve alignment of treatment choices with KOLs. [Table: see text]

A phase II trial of TAS-102 in patients with colorectal cancer with ctDNA-defined minimal residual disease post-adjuvant therapy compared to synthetic control cohort: Results from the MD Anderson INTERCEPT program.

3623 Background: Circulating tumor DNA (ctDNA) has emerged as a novel marker with high specificity and positive predictive value for identifying radiographically occult minimal residual disease (MRD) in colorectal cancer (CRC) patients (pts). A widely acknowledged unmet need is the development of therapeutic strategies to eradicate MRD and increase the cure rate of the disease. Ongoing trials are evaluating MRD as a biomarker for determining the intensity of post-operative adjuvant therapy. However, the feasibility and efficacy of therapy in pts who are MRD+ during surveillance (after all curative intent treatments including adjuvant chemotherapy) is unknown. Methods: In this phase II study, pts with stages II-IV CRC noted to be MRD+ during surveillance (ctDNA+ but no radiographic evidence of disease on imaging in last 30 days) received 6 months (m) of TAS-102. Pts were identified through the MD Anderson INTERCEPT program that integrates MRD testing with a tissue informed assay (Signatera) into standard of care for CRC pts. The primary endpoint was 6-m ctDNA clearance and secondary endpoints included 3-m ctDNA clearance, and disease-free survival (DFS). For comparison, a synthetic cohort (SC) was retrospectively created through the MD Anderson INTERCEPT Program of MRD+ pts not enrolled in MRD trials. Pts in the SC were matched by stage, BRAFmt status, MSI-H status, and treatment history. Results: Between 7/22/22 and 11/7/23, 15 MRD+ pts were enrolled and received TAS-102. Baseline characteristics included a median age of 62 (range: 37-73), resected Stage IV (80%), MSS (100%), BRAF wildtype (100%) and neoadjuvant therapy (87%). 30 pts were included in the SC and baseline characteristics included median age of 57 (range: 32-79), resected stage IV (80%), MSS (100%), BRAF wildtype (100%) and neoadjuvant therapy (90%). At data cutoff, 14 pts receiving TAS-102 had 3-m ctDNA levels. 7 pts (50%) had undetectable ctDNA levels at 3-m compared to 2 pts (6.7%) in the SC (p=0.0022). 12 had a decrease in their ctDNA level (86%) compared to 5 (17%) in the SC (p<0.0001). At 6-m, 82% of pts on trial had ctDNA levels at or below prior levels. 5 pts (45%) maintained undetectable ctDNA at 6-m compared to 2 pts (6.7%) in the SC (p=0.0096). Median DFS was 9.4-m with TAS-102 compared to 5.8-m in the SC. Conclusions: It is possible to identify MRD+ pts through screening during surveillance and enroll them onto therapeutic trials. Preliminary results suggest that treatment with TAS-102 is effective in inducing ctDNA clearance in the short term, and in doing so, may prolong DFS for pts receiving additional therapy compared to the SC. However, without evidence of persistent clearance this is unlikely to result in an increased cure fraction. Updated results, including survival data, will be presented. Clinical trial information: NCT05343013 .

Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: Overall survival and updated 5-year results from the randomized DYNAMIC trial.

108 Background: Previous results of the DYNAMIC study demonstrated that a ctDNA-guided approach versus standard management in stage II colon cancer (CC) reduced adjuvant chemotherapy (ACT) use without compromising 2-year recurrence-free survival (RFS). MMR status defines two distinct subsets of stage II CC. Here, we report the impact of ctDNA burden, end of ACT (EOT) ctDNA, and updated survival data including overall survival (OS). Methods: DYNAMIC is a multi-center randomized phase II trial. Eligible patients (pts) had resected stage II CC and were suitable for ACT. Pts were randomly assigned 2:1 to ctDNA-guided management or standard management (clinician-guided based on conventional criteria). For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery with a tumor-informed assay prompted oxaliplatin-based or fluoropyrimidine ACT; ctDNA-negative pts were not treated. Between Aug 2015 and Aug 2019, 302 received ctDNA-guided and 153 standard management. The primary endpoint was RFS, with a non-inferiority margin of 8.5%. Pre-specified key secondary endpoints were ACT use and OS, with an additional secondary endpoint of ctDNA clearance rate. Results: With a median follow-up of 59.6 months (IQR 55.0–61.5), 5-year RFS were 88% and 87% with ctDNA-guided and standard management, respectively (difference 1.1%, 95% confidence interval, -5.8% to 8.0%). 5-year OS for ctDNA-guided treatment was 93.8% and standard management 93.3% (HR 1.05; 95% CI, 0.47 to 2.37; P = 0.887). 5-year OS was significantly worse in treated ctDNA-positive versus untreated ctDNA-negative pts (85.6% vs 95.3%, HR 3.30; 95% CI, 1.02 to 9.05; P = 0.014). The 5-year OS for ctDNA-negative T3 and T4 disease were 96.0% and 90.6%, respectively (HR 2.45; 95% CI, 0.65 to 9.25; P = 0.171). For treated ctDNA-positive pts, ctDNA clearance was observed at EOT in 35/40 (87.5%). The 5-year RFS for EOT ctDNA clearance vs ctDNA persistence were 85.2% and 20.0%, respectively (HR 15.4; 95% CI, 3.91 to 61.0; P < 0.001). Pts with ≥ 0.38 (the median) mutant tumor molecules (MTM/mL) had a lower ctDNA clearance rate and worse RFS than pts with < 0.38 MTM/mL (ctDNA clearance 75% vs 100%, P = 0.047; 5-year RFS 58.9% vs 95.2%, HR 10.62, P = 0.005). Post-op ctDNA was detected in 5/59 (8.5%) of dMMR and 40/235 (17%) of pMMR cases. In an exploratory analysis, ctDNA clearance was observed in 3/4 (75%) and 32/36 (89%) of dMMR and pMMR cases, respectively. Conclusions: Mature outcome data confirms the previous finding of non-inferiority of RFS with a ctDNA-guided approach to ACT for stage II CC. For ctDNA-positive pts, the post-surgery mutation burden provides additional prognostic information, as does the EOT ctDNA result. Additional data is needed to define any differential impact of ACT by MMR status. This data supports a role for ctDNA analysis, including serial sampling, in the management of stage II CC. Clinical trial information: ACTRN12615000381583 .

Serum multiplex analysis of checkpoint proteins in association with immune-related adverse events in patients with melanoma receiving adjuvant anti-PD-1 therapy.

9588 Background: Immune checkpoint inhibitors have significantly improved melanoma (MEL) patient (PT) outcomes. Immune-related adverse events (irAEs) may cause significant morbidity, rarely including death. Soluble immune checkpoints have been identified as biomarkers of autoimmune activity and potential off-target pathology. Understanding their relationship to pathologic outcomes may assist in the identification of PTs at highest risk of irAEs. Methods: PTs with resectable stage IIB-IV MEL who received adjuvant anti-programmed-death-1 (PD-1) therapy were identified from the University of Pittsburgh’s MEL Center biospecimen repository (N=273). MILLIPLEX Human Immuno-Oncology Checkpoint Protein Panel 2 was used to study serum levels of immunomodulatory proteins. Mean pretreatment serum levels in PTs with and without irAEs were compared using a two-sample t-test after performing Box-Cox transformation for non-normally distributed data. Results: Sera from 43 PTs were analyzed. The cohort included 28 (65.1%) male, mean age at diagnosis (62), including MEL stage IIIA = 7 (16.3%), IIIB = 16(37.2%) and IIIC = 20(46.5%). The most common irAEs (n=24, 55.8%) were thyroiditis (n=9, 20.9%), dermatitis (n=8, 18.6%), and adrenal insufficiency (n=9, 21.0%). Multiple irAEs were observed amongst 22 (51.2%) PTs with ≥3 irAEs and 6 (13.9%) with 5 irAEs. Visceral irAEs included Hepatitis (n=3, 7.0%), pneumonitis (n=2, 4.7%), and colitis (n=5, 11.6%). Seven of 8 patients with visceral irAEs required corticosteroids. Siglec-7 (mean 23.4 vs 3.51 pg/mL, p=0.018) and siglec-9 (mean 77.0 vs 33.1 pg/mL, p=0.049) were significantly elevated in the PTs who developed any irAE. After stratifying for each individual irAE, PTs with thyroiditis had elevated Nectin-4 (mean 2785.5 vs 494.7 pg/mL, p<0.001) and serum arginase (mean 2437.5 vs 1383.1 pg/mL, p= 0.046) was elevated in PTs who developed colitis. PTs with hepatitis demonstrated increased galectin-3 (mean 10103.9 vs 9915.3 pg/mL, p=0.045) and decreased levels of CD40L (mean 2869.2 vs 9496.9 pg/mL, p=0.033). In PTs with dermatitis B7-H3 (mean 2503.3 vs 732.4 pg/mL, p=0.009) and MHC class I polypeptide-related sequence B (mean 1598.0 vs 259.1 pg/mL, p=0.048) were elevated. Conclusions: We have demonstrated unique serum checkpoint protein profiles related to specific irAEs in melanoma patients receiving adjuvant anti-PD1. Further studies are warranted to confirm and validate the utility of these irAE predictors during adjuvant anti-PD-1.

ALK testing patterns in early-stage non-small cell lung cancer: A real-world evidence study.

8074 Background: Comprehensive biomarker testing in advanced non-small cell lung cancer (aNSCLC) is standard of care, but disparities exist. As new clinical data emerge in early disease (eNSCLC), the set of actionable lung driver mutations (LDMs) and therefore the testing landscape in that setting will change. In particular, following the results of the ALINA trial, therapies that target ALK fusions are anticipated to become part of routine treatment of eNSCLC in 2024.This study thus sought to identify the factors associated with receipt of timely ALK testing in eNSCLC, prior to this shift. Methods: We retrospectively analyzed patients with resected stage I-IIIa NSCLC diagnosed between 2018-2023 using the expanded nationwide (US-based) de-identified Flatiron Health EHR-derived database; data were consolidated from approximately 280 US cancer clinics (≅800 sites of care), using natural language processing with machine learning (ML) to extract patient characteristics. The primary endpoint was ALK testing results (by any modality) within 90 days of initial diagnosis. We used multivariable logistic regression to assess the association between clinico-demographic characteristics and likelihood of testing. Results: The sample contained 21,982 stage I-IIIa patients. Of these, 6,685 (30%) were tested within 90 days, and 15,297 (70%) were not. Patients were more likely to be tested within 90 days if they were diagnosed in more recent years (2023 vs. 2018 odds ratio (OR) 2.12); had no history of smoking (OR 1.21); had highest socioeconomic status (SES) quintile (OR vs. lowest SES 1.14); had more advanced disease (stage IIIa vs. stage I OR 2.43); or were treated in a community setting (OR vs. academic 1.13), all p < 0.05. Patients with Medicare insurance (OR vs. commercial insurance 0.89, p = 0.014) or squamous histology (OR vs. non-squamous 0.46, p < 0.01) were less likely to be tested. There were no significant differences between black and white patients (OR 0.91, p = 013). Conclusions: In this real-world analysis of patients diagnosed between 2018-2023 most patients did not have testing within 90 days of diagnosis. Our data show variation in the baseline probability of testing with respect to clinico-demographic factors. Given that barriers to testing persist in aNSCLC, this suggests that once ALK inhibitors become part of routine care in eNSCLC, some groups might be less likely to be tested and therefore to receive efficacious targeted treatment. Preemptive measures such as education of patients, providers, payers, and policy makers could help prevent disparities from emerging.

Neoadjuvant pembrolizumab plus lenvatinib in patients with resectable stage III melanoma (NeoPele): Analysis of tumor microenvironment (TME) correlated to pathological response.

9566 Background: The phase II SWOG S1801 study showed an improved event-free survival with anti-PD-1 (PD1) neoadjuvant immunotherapy (neoIT) vs adjuvant PD1. One hypothesis explaining this benefit is the presence of tumor-draining lymph nodes (tdLN; defined as the nearest node to the tumor without direct involvement) as a potential reserve of stem-like (TCF7+) T cells, crucial to a good response to IT. We sought to analyze the immune infiltrate of the tumor-involved LN (ie TME) and tdLN from patients (pts) achieving major pathological response (MPR: complete [pCR] or near-complete [near-pCR] pathological response) vs non-MPR (partial [pPR] or no [pNR] pathological response). Methods: Pts with stage III melanoma treated with 6 weeks of PD1-based neoIT (PD1 + Lenvatinib) were included (NeoPele clinical trial; NCT04207086). Multiplex fluorescent immunohistochemistry of the TME before and after neoIT, and of the tdLN after neoIT was analyzed (T cell panel: CD3, TCF7, CD103, FoxP3, CD39 and Sox10; and B cell panel: CD20, CD21, CXCR5, TCF7, CD3 and SOX10). Lymphoid aggregates, characterized by clusters of CD21+ and CXCR5+ immune cells, were quantified. Results: Of the 20 pts, 11 (55%) had MPR (8 [40%] with pCR and 3 [15%] with near-pCR) and 9 (45%) had a non-MPR (4 [20%] with pPR and 5 [25%] with pNR). At baseline, MPR pts had a higher % of T cells (11% vs 3%, p = 0.0127) and follicular B helper T cells (CXCR5+; 29% vs 9%, p = 0.0293) than non-MPR pts in the TME. NeoIT led to an increase in the % of T cells, mainly in pts with MPR (median +30%; p = 0.0156) vs non-MPR (median +7%; p = 0.0312) pts, including an increase in the % of tumor-reactive (CD39+) T cells (p = 0.0195), but a decrease in % of tissue-resident stem-like (CD103+ TCF7+) T cells (p = 0.0195). Within the B cell compartment, there was an increase in the % of CD21+ B cells and mature (CD21+ CXCR5+) B cells in MPR vs non-MPR pts. At week 6, MPR pts maintained a higher % of T cells (36% vs 11%, p = 0.0172), follicular B helper T cells (20% vs 9%, p = 0.0133), and mature B cells (10% vs 2%, p = 0.0021) in the TME compared with non-MPR. NeoIT led to a significant increase in the number of lymphoid aggregates in the TME from MPR pts (median +42; p = 0,0156), but no difference in non-MPR pts. No differences were observed in the tdLN based on pathological response. Conclusions: MPR pts had a higher density of T cells in the TME at baseline, and a more differentiated and activated immune profile after neoIT compared with non-MPR pts. MPR pts had a significant increase in the number of lymphoid aggregates at week 6 compared to non-MPR pts; however, the role of these lymphoid aggregates, including the follicular B helper T cell subset and mature B cells, promoting a good pathological response to neoIT is yet to be clarified. Clinical trial information: NCT04207086 .

Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA): NRG-GI008.

TPS3641 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage IIB, IIC, and III CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines vserial ctDNA monitoring. Patients who are ctDNA+ post-operatively, or with serial monitoring (Cohort B), will be randomized to FP+Ox v more intensive AC with addition of irinotecan (I) for 6 mos. One cycle of chemotherapy is allowed while awaiting ctDNA testing results for cohort assignment. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate v delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox v FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022 with CCTG sites joining in August 2023. Current accrual (as of 02-02-2024) is 240/1,912. NCT05174169. Support: U10-CA-180868, -180822; UG1CA-189867; Natera, Inc. Clinical trial information: NCT05174169 .

Toripalimab (anti-PD-1) plus recombinant human endostatin as adjuvant therapy in patients with resected stage III melanoma: Interim analysis of an open-label phase II trial.

e21557 Background: Patients with completely resected stage III melanoma are under high risk of disease recurrence. Recurrence-free survival (RFS) remains unsatisfactory despite there is adjuvant anti-PD-1 monotherapy following surgery, with the 1-year RFS about 70% and 2-year RFS about 49% in our country. It's urgent to explore combined regimens with anti-PD-1 to further improve the RFS. Here we report the interim efficacy and safety results of toripalimab (a PD-1 inhibitor) plus recombinant human endostatin (an angiogenesis inhibitor) as combined adjuvant therapy for patients with resected stage III melanoma. Methods: This prospective single-center, single-arm, open-label phase II trial screened adult patients with stage III melanoma who had undergone complete tumor resection within the previous 13 weeks for eligibility. Toripalimab was administrated in intravenous drip to patients at 3 mg/kg every 2 weeks in a 4-week cycle (day 1 and day 15 of each cycle), for up to 13 cycles or until disease recurrence, unacceptable toxicity or decease. Recombinant human endostatin was administrated in a continuous intravenous infusion at a dose of 210 mg from day 1 to day 3 for each 4-week cycle, for up to 6 cycles or until disease recurrence, unacceptable toxicity or decease. The primary endpoints were the 1-year and 2-year RFS. Results: By the data cut-off on Jan 25, 2024, 43 eligible patients with resected stage III melanoma between October 2021 and December 2023 were enrolled. In ITT population (n = 43), patients' median age was 56 (IQR 52~69) years. There were 25 (58%) male and 18 (42%) female; 27 (63%) with acral melanoma and 16 (37%) with cutaneous melanoma. With a median follow-up of 14 months, the 1-year and 2-year RFS rates were 83% and 71%, respectively. For security, 33 (77%) patients experienced at least one adverse event (AE), including 27 grade 1-2 AEs and 6 grade 3~4 AEs. One patient discontinued the combined therapy due to immunotherapy-associated myocarditis. Conclusions: Toripalimab in combination with recombinant human endostatin as adjuvant therapy could further improve disease-free survival in Chinese patients with completely resected stage III melanoma, with a manageable toxicity profile. Clinical trial information: 05907512 .

Phase II study of induction platinum doublet in combination with nivolumab followed by surgery or concurrent chemotherapy-nivolumab-radiation in unresectable stage IIIA-C non-small cell lung cancer (NSCLC).

TPS8122 Background: For patients (pts) with stage IIIA-IIIC NSCLC, though standard of care chemo-radiation (XRT) followed by 1 year of durvalumab has improved 5 year overall survival (OS), fewer than 50% survive 5 years. In this study, we adopted the established neoadjuvant chemotherapy (chemo) plus nivolumab (nivo) CheckMate-816 regimens for resectable stage I(>4cm)-IIIA yielding an increased complete pathologic response (pCR) rate and event free survival compared to chemo alone, as induction therapy in unresectable stage IIIA-IIIC NSCLC. The intent is to use induction chemo-nivo to treat pts traditionally considered unresectable (multi-station N2 or N3 disease) in order to downstage them enough to permit surgical resection. The study is structured to change (1) the immune checkpoint inhibitor (ICI) regimen to induction rather than consolidation which enables the chance to observe the systemic therapy’s efficacy, treat micro-metastatic disease earlier, and may decrease the morbidity of the ablative therapies (2) the ICI containing regimen by increasing from single agent ICI to combination chemo plus nivo which may improve systemic efficacy (3) the duration of treatment with pre and post ablative ICI containing therapy.Induction also provides a platform for studying tumor biology with the chance to discover surrogate markers of response and resistance to the induction regimen matched against response ahead of the definitive therapy. Methods: This is an investigator initiated trial for pts with newly diagnosed clinical stage IIIA-IIIC EGFR/ALK/ROS1 WT, SQ and NSQ NSCLC with PS 0-1. Pts must be able to tolerate surgery and have a primary tumor which is technically resectable with an N stage IIIA > 2 or more lymph node (LN) stations positive. Pts are treated with the same platinum doublet plus nivo regimens used in CheckMate-816 for 3 cycles followed by repeat CT and repeat biopsy of all LN stations biopsied at baseline and LN stations which at baseline had a high suspicion of harboring disease and which look technically unresectable. If the cancer is down-staged to a single LN station-N2, or is N1 or N0, the pt is offered surgery with an option of post-operative XRT. If not sufficiently down-staged, pts are treated with definitive chemo-nivo-XRT. All pts receive 1 year of consolidation nivo. The primary outcome is response to the induction regimen by repeat CT scan. Secondary outcomes include the rate of converting non-surgical stage III(A-C) to surgically resectable disease, pCR rate, extent of post-induction XRT field decrease, 2-year progression free survival, OS, quality of life, and exploratory outcomes include markers of resistance and response, and remote symptom monitoring. Enrolment will be 37 pts. The study is accruing with a plan to open at a second site. Clinical trial information: NCT06003075 .

Comparison of the efficacy of immunotherapy at different time points during the perioperative period for stage II-III NSCLC.

e20009 Background: The application of immune checkpoint inhibitors (ICIs) in early-stage lung cancer is fraught with unresolved issues, and there are no clinical studies directly comparing the efficacy of ICIs used in neoadjuvant, adjuvant, and neoadjuvant followed by adjuvant therapy across different perioperative time points in non-small cell lung cancer (NSCLC). Consequently, the optimal timing for immunotherapy in surgically resectable NSCLC remains uncertain. Methods: This study encompassed 536 patients with stage II-III NSCLC, diagnosed and treated across multiple centers from January 2019 to December 2022. Clinical data for all patients ultimately included in the study were retrospectively collected. The primary endpoints evaluated were event-free survival (EFS)/disease-free survival (DFS) and overall survival (OS) . Secondary endpoints included pathological complete response (pCR) and major pathological response (MPR). Propensity score matching was utilized to mitigate confounding factors, comparing the efficacy of ICIs across different treatment modalities and time dimensions during the perioperative period of lung cancer. Results: The integration of neoadjuvant ICIs with chemotherapy was observed to significantly enhance pCR ( p < 0.001), MPR ( p < 0.001), EFS ( p = 0.002), and OS ( p < 0.001) in comparison to neoadjuvant chemotherapy alone. Similarly, the combination of adjuvant ICIs with chemotherapy markedly improved DFS ( p = 0.034) and OS ( p = 0.021) relative to adjuvant chemotherapy alone. Building on these insights, we further delineated the efficacy of ICIs across distinct temporal dimensions within the perioperative interval, categorizing patients into three groups: neoadjuvant ICIs plus chemotherapy, adjuvant ICIs plus chemotherapy, and a sequential regimen of neoadjuvant followed by adjuvant ICIs plus chemotherapy. The analysis revealed no significant differences in DFS and OS among the three patient groups for stage II NSCLC. In contrast, for stage III NSCLC, both neoadjuvant ( p = 0.015) and sequential treatment approaches ( p = 0.047) demonstrated significantly improved DFS outcomes compared to the adjuvant protocol, with no substantial statistical difference noted between the neoadjuvant and sequential treatments ( p = 0.274). Furthermore, the sequential regimen outperformed the adjuvant strategy in OS ( p = 0.020). However, when comparing the neoadjuvant strategy with either the adjuvant ( p = 0.054) or sequential approaches ( p = 0.717), there were no statistically significant variances detected. Conclusions: For individuals with resectable stage III NSCLC, perioperative administration of neoadjuvant and sequential adjuvant ICIs appears to confer enhanced survival advantages. Future efforts should focus on refining treatment strategies for early-stage NSCLC, aiming to deliver enhanced survival benefits to patients.

Health-related quality of life (HRQoL) outcomes from the randomized, double-blind phase 3 KEYNOTE-671 study of perioperative pembrolizumab for early-stage non-small-cell lung cancer (NSCLC).

8012 Background: Neoadjuvant pembrolizumab + cisplatin-based chemotherapy (neoadj pembro + chemo), resection, and adjuvant (adj) pembro (pembro arm; n=397) significantly improved EFS, OS, pCR, and mPR and had an expected safety profile versus neoadj placebo (pbo) + chemo, resection, and adj pbo (pbo arm; n=400) in patients (pts) with resectable stage II, IIIA, or IIIB (N2) NSCLC. We present prespecified pt-reported outcome (PRO) endpoints from KEYNOTE-671. Methods: Pts completed EORTC QLQ-C30 and QLQ-LC13 questionnaires at baseline (BL), the last scheduled presurgery visit, adj cycles 1-4, 7, 10, and 13, and each post treatment visit. A constrained longitudinal data analysis model was used to estimate least squares mean (LSM) score changes from BL to neoadj wk 11 and adj wk 10 (latest time of ≥60% completion and ≥80% compliance) in QLQ-C30 global health status (GHS)/QoL, physical functioning (PF), role functioning (RF), and dyspnea and QLC-LC13 cough and chest pain in all treated pts who completed ≥1 PRO assessment. Data are from interim analysis 2 (10 Jul 2023 cutoff). Results: Across arms, questionnaire completion was ≥87% at neoadj wk 11 and ≥62% at adj wk 10; compliance was ≥87% and ≥92%, respectively. There were no differences in LSM change from BL in the neoadj or adj phase for any PRO score (Table). Conclusions: Adding perioperative pembro maintained HRQoL in both the neoadj and adj settings versus neoadj chemo and surgery alone in pts with resectable early-stage NSCLC. Together with the significant efficacy improvements and absence of new safety signals, HRQoL data support the perioperative pembro regimen as a new standard of care. Clinical trial information: NCT03425643 . [Table: see text]

Neoadjuvant camrelizumab combined with chemotherapy for resectable stage IIIA-IIIb non-small cell lung cancer: Single arm phase II study.

e20074 Background: This study aimed to evaluate the safety and efficacy of neoadjuvant camrelizumab combined with chemotherapy in patients with resectable non-small cell lung cancer (NSCLC). Methods: In this single-arm phase II clinical trial, patients aged 18-75 with pathologically confirmed resectable stage IIIA-IIIB (T3-4N2) NSCLC without EGFR, ALK, and ROS1 gene mutations were enrolled since December 2022. Patients were assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2 or pemetrexed (for adenocarcinoma), 500mg/m2 plus platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5]). Radical surgery was performed within 4-6 weeks after neoadjuvant therapy. Patients undergo 18F-fluorodeoxyglucose (FDG) PET/CT scans within 1 week before treatment and surgery, respectively. The primary endpoints for follow-up are pathologic complete response (pCR) rate and major pathological response (MPR) rate, while secondary endpoints include safety and disease-free survival (DFS). Exploratory endpoints include molecular imaging research and biomarker analysis. Results: Up to December 2023, 30 patients (median age: 64 years) have been enrolled, including 22 cases of squamous carcinoma and 8 cases of adenocarcinoma. All patients received 3 cycles of neoadjuvant camrelizumab plus chemotherapy, and 27 patients underwent radical sugery. Three patients did not receive surgical treatment, 2 of whom refused surgery and 1 was unable to undergo surgery due to disease progression. Among patients received surgery, 27 (100%) achieved R0 resection, 10 (37.0%) achieved pCR, and 15 (55.6%) achieved MPR. For patients with squamous cell carcinoma, the MPR and pCR rates were 70% (14/20) and 45% (9/20), respectively, while for adenocarcinoma patients, the MPR and pCR rates were 14.3% (1/7) and 14.3% (1/7), respectively. There was no significant difference in pathological response rates between the PD-L1 tumor proportion score (TPS) ≥ 1% group and the PD-L1 TPS < 1% group. Most of treatment-related adverse events (TRAEs) were grade 1-2, and the most common TRAEs was leukopenia (63.0%). Five patients (18.5%) developed grade ≥ 3 TRAEs, including 3 leukopenia, 1 neutropenia, and 1 pneumonia. Biomarker analysis showed that among patients with pCR, the proportion of increased circulating M1 macrophages and decreased mononuclear myeloid-derived suppressor cells (M-MDSCs) and M2 macrophages after treatment was higher than those in non-pCR patients. Circulating ctDNA analysis showed that the ctDNA concentration of patients with non-pCR after treatment was higher than that of patients with pCR. Patients with ctDNA remaining positive after treatment were all in the non-pCR group. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy for NSCLC patients show promising pathological response rates and tolerable safety. Clinical trial information: NCT06241807 .

A randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153.

TPS8118 Background: Each year, approximately 35,000 patients are diagnosed with stage I lung cancer in the United States. Despite early detection, the 5-year overall survival for this population remains disappointing, ranging between 73-86% with recurrence rates from 18-38%. The current standard of care for stage I NSCLC is surgery alone followed by observation as prior trials of adjuvant chemotherapy in this subgroup have failed to show benefit. More modern therapies such as programmed death-1 (PD-1) inhibitors have not been evaluated in the stage I setting but have demonstrated significant improvements in pathologic complete response, event free survival, and overall survival when added to chemotherapy for patients with fully resected stage II and III disease. The use of PD-(L)1 inhibition has also demonstrated clinically and statistically significant improvements in OS in both unresectable stage III NSCLC following chemoradiation and in the metastatic setting. Given the activity of PD-(L)1 inhibition in nearly every other subset of NSCLC patients, we aimed to evaluate this therapy following resection in stage I NSCLC patients. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial randomizes patients 1:1 to either Pembrolizumab 400mg IV every 6 weeks for up to 9 cycles or observation alone. Patients are stratified by PD-L1 score (PD-L1 ≥50% vs. < 50%) and tumor size (1-2cm vs. > 2-4cm), and they undergo repeat CT imaging every 12 weeks. The study is being conducted through the Big Ten Cancer Research Consortium, and there are currently 11 sites open to accrual with one additional site pending activation. The primary endpoint is disease free survival with secondary endpoints including OS, DFS at multiple timepoints (1-, 2-, and 3-years), and safety. The trial initially opened to accrual at the lead site, Indiana University, in May 2020, and enrollment is currently at 95 patients with a planned enrollment of 244. (NCT04317534) Clinical trial information: NCT04317534 .

A phase 2, open-label, 2-cohort study to evaluate patient preference for nivolumab (NIVO) + relatlimab (RELA) fixed-dose combination (FDC) subcutaneous (SC) vs NIVO + RELA FDC intravenous (IV) and NIVO SC vs NIVO IV in participants with melanoma.

TPS9619 Background: The oncology burden on healthcare resources and patients increases as the number of individuals with cancer grows, necessitating treatment options offering improved convenience to patients. SC delivery of monoclonal antibodies in various cancer indications has previously been shown to be effective, well tolerated, and preferred by patients over IV infusion. In CheckMate 67T (NCT04810078), noninferiority of exposure (time-averaged serum concentration at Day 28 and trough serum concentration at steady state) and efficacy (objective response rate by BICR) were previously reported for NIVO SC 1200 mg + recombinant human hyaluronidase PH20 (rHuPH20) vs IV in patients with locally advanced/metastatic clear cell renal cell carcinoma. RELATIVITY-127 (NCT05625399) is ongoing to establish exposure noninferiority of NIVO + RELA + rHuPH20 FDC SC to IV in patients with previously untreated metastatic/unresectable melanoma. This phase 2, open-label study CA224-1044 (NCT06101134) assesses patient preference for NIVO SC or NIVO + RELA FDC SC vs IV formulations after transitioning from IV to SC in patients with melanoma and aims to further characterize the safety profile of immuno-oncology therapy during IV-to-SC switch. Methods: Cohort 1 includes adult patients with previously untreated stage III (unresectable) or stage IV (metastatic) melanoma who will receive NIVO + RELA FDC IV every 4 weeks (Q4W) for 2 cycles (28-day cycle) followed by NIVO + RELA + rHuPH20 FDC SC Q4W until disease progression, unacceptable toxicity, or a maximum total treatment duration of 2 years, whichever comes first. Cohort 2 includes adult patients with completely resected stage IIB/C, stage III or stage IV melanoma who will receive NIVO IV Q4W for 2 cycles (28-day cycle) followed by NIVO SC + rHuPH20 Q4W until disease recurrence, unacceptable toxicity, or a maximum total treatment duration of 1 year, whichever comes first. The primary endpoint is the proportion of participants preferring the SC route of administration based on question 7 of the Patient Experience and Preference Questionnaire after the Cycle 4 Day 1 dose. This question evaluates patient preference for IV or SC or no preference in treatment administration and was previously used in CheckMate 8KX. Secondary endpoints include safety outcomes such as adverse events (AEs), serious AEs, treatment-related AEs, AEs leading to discontinuation, immune-mediated AEs, other events of special interest, injection/infusion-related AEs, deaths, and laboratory abnormalities. Safety is assessed for IV period, SC period (8 weeks each) and overall study period. Exploratory endpoints include additional measures of patient experience and preference for IV vs SC. The study is recruiting to enroll 50 patients per cohort. Clinical trial information: NCT06101134 .

Health-related quality of life (HRQoL) results for adjuvant alectinib vs chemotherapy in patients with resected ALK+ non-small cell lung cancer (NSCLC): Data from ALINA.

8006 Background: ALINA (NCT03456076) is a global, open-label, phase 3, randomized trial evaluating the efficacy and safety of adjuvant alectinib versus chemotherapy in patients with resected stage IB (≥4 cm)–IIIA, ALK+ NSCLC. A significant disease-free survival benefit was observed with alectinib vs chemotherapy (HR 0.24, 95% CI: 0.13–0.43, p<0.0001; N=257 patients in the ITT). In the adjuvant setting, where patients have received surgery with curative intent, the impact of treatment on HRQoL is an important clinical consideration. We report HRQoL results from ALINA. Methods: Patients ≥18 years old with ECOG PS 0/1 and completely resected, stage IB–IIIA, ALK+ NSCLC (UICC/AJCC 7th edition) were randomized 1:1 to receive oral 600 mg alectinib twice-daily for 2 years, or four 21-day cycles of platinum-based chemotherapy. HRQoL was an exploratory endpoint measured using the Short Form-36 version 2 (SF-36v2) health survey, which assesses functional health and well-being across 8 domains and 2 aggregated summary scores: the physical (PCS) and mental (MCS) component summary scores. Patients completed the SF-36v2 at baseline, every 3 weeks to Week 12, then every 12 weeks until disease recurrence, withdrawal of consent, death, or Week 96 (or equivalent post-chemotherapy follow-up visit). SF-36v2 was scored using norm-based scoring relative to the 2009 US general population (mean ± standard deviation: 50 ± 10), with higher scores indicating better health. Within-group minimal important differences (MIDs) were used as benchmarks for each domain, MCS and PCS. Data cut-off: 26 June 2023. Results: Completion rates were generally high (>90%) throughout the study. At baseline, most mean scores were low (<50) and were similar between study arms. With alectinib, mean scores were ≥50 for the Bodily Pain, Mental Health and Vitality domains by Week 96, suggesting that patients functioned as well as the general population on these aspects. The mean change from baseline met or exceeded MIDs for 5 domains and MCS by Week 12, and exceeded MIDs for 6 domains, MCS and PCS by Week 96. In the chemotherapy arm, mean scores were low during treatment; mean change from baseline for General Health and Vitality exceeded negative MIDs, indicating worsening in these domains. Mean scores improved in the post-chemotherapy period; in the final assessment, mean scores were ≥50 for the Bodily Pain, Mental Health and Vitality domains, and MIDs were met or exceeded for MCS, PCS and 5 domains. Conclusions: Alectinib demonstrated an improvement in most domains of HRQoL by Week 12, followed by maintenance of HRQoL on all 8 domains, MCS and PCS to Week 96. With chemotherapy, HRQoL was low during treatment, but improved in the post-chemotherapy period. Together with the DFS benefit seen in ALINA, these data support alectinib as an important new adjuvant treatment for patients with resected ALK+ NSCLC. Clinical trial information: NCT03456076 .