Significant Overall Survival Benefit Research Articles

Abstract 3818: Sociodemographic, access to care and survival outcomes for patients with mantle cell lymphoma: A national cancer database analysis with focus on Hispanics

Abstract Background: Mantle cell lymphoma (MCL), represents 3% of new cases of non-Hodgkin’s lymphomas.(PMID 29348844) MCL affects mainly males; factors like ethnicity, age at presentation can have prognostic implications. Currently, it isn’t clear if Hispanics (HI) have a survival difference compared to Non-Hispanics (NH).(PMID 31029647, PMID 25315847). This National Cancer Database (NCDB) analysis aims to clarify how sociodemographic factors affect presentation and survival in HI vs NH patients with MCL. Methods: Data were analyzed on MCL patients in the United States reported to the NCDB 2004-2019. Demographic and treatment characteristics were compared between ethnic groups. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS). Multivariate analysis and propensity score matching was performed. Results: Of 32515 of MCL patients, 1729 were HI, and 29309 NH. Male gender and identification as white predominated for both. HI were diagnosed at a younger median age of 65 years (y) vs 68 y for NH, p<0.001. Most patients were diagnosed between years 2016-2019. Stage IV predominated for HI and NH, p<0.001. As to Charlson-Deyo Score ≥2, HI had 6% vs NH 8%. Government sponsored was the most prevalent primary payer, HI (54%) and NH (60%). HI had a higher percentage of unknown/uninsured, 13% vs 4% for NH, p<0.001. In relation to census median income (2008-2012), the most prevalent bracket for HI and for NH was >$63,000, 29% and 37% respectively. When analyzing median income of less than $38,000, HI were 22% vs 13% for NH, p<0.001. For median distance in miles (mi) between the patient’s residence and the hospital that reported the case (Great circle distance), HI lived at a median of 8.2mi, vs NH at median of 11.3mi. Most patients were treated at Academic/Research programs, 50% for HI and 39% for NH, p<0.001. On survival analysis, the survival probability at 2, 5 and 10 for HI was 74%, 57%, 44%, vs for NH was 72%, 54%, 36%, respectively. The median survival (MS) was 7.0 years for HI, vs 5.8 years for NH, with a statically significant difference in OS favoring HI, p=0.00015. On multivariate analysis, not insured status was independently associated with worse OS (HR 1.29, CI 1.08-1.55, p=0,01). The propensity matched analysis showed significant MS difference between HI vs NH (5.8 y vs. 5.6 y). Conclusion: In this analysis, MCL is a malignancy that presents at advanced stages, affecting mainly the elderly white males. HI compared to NH have a statically significant benefit in OS, which might be driven by a younger population with less comorbidities. Despite HI having limited access to insurance and lower income; sociodemographic differences don’t seem to be barriers for HI to access care at academic centers. Newer studies should focus on understanding what genetic and intrinsic disease factors cause HI to have an earlier presentation and a survival advantage over NH. Citation Format: Esteban Toro Velez, Carolina Velez-Mejia, Daniel Rosas, Qianqian Liu, Joel Michalek, Adolfo Enrique Diaz Duque. Sociodemographic, access to care and survival outcomes for patients with mantle cell lymphoma: A national cancer database analysis with focus on Hispanics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3818.

Abstract 6118: Sex-related disparity in immune checkpoint inhibitor benefit for patients with esophageal squamous cell carcinoma: A systematic review and meta-analysis

Abstract Sex-related dimorphism in cancer incidence and immune response is widely recognized, yet the impact of an individual's sex on the effectiveness of Immune Checkpoint Inhibitors (ICIs) for patients with advanced esophageal squamous cell carcinoma (ESCC) remains poorly understood. In this study, we conducted a comprehensive meta-analysis to evaluate the heterogeneity of ICIs in patients with advanced ESCC. We collected studies from PubMed, MEDLINE, Embase, and Scopus, spanning from the inception of the databases to September 30, 2023. These studies focused on phase III randomized trials comparing first-line ICIs (PD-1/PD-L1) plus chemotherapy with chemotherapy alone for advanced or metastatic ESCC. Additionally, we reviewed abstracts and presentations from AACR, ASCO, ESMO, and WCLC. Inclusion criteria mandated the reporting of overall survival (OS) data stratified by sex and nonselective baseline PD-L1 expression. The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The analysis included 6 randomized clinical trials comprising 3603 ESCC patients, of whom 3090 (85.8%) were male and 513 (14.2%) were female. A significant OS benefit was observed for ICIs plus chemotherapy in all patients (HR, 0.68; 95% CI, 0.62-0.74; P < 0.001). Similarly, ICIs plus chemotherapy correlated with a significantly prolonged OS in males (HR, 0.67; 95% CI, 0.61-0.74, P < 0.001). However, there was no significant OS benefit observed in females with ICIs plus chemotherapy (HR, 0.79; 95% CI, 0.58-1.09; P = 0.148). Females had a tendency toward less benefit than males (pooled HR, 1.18; 95% CI, 0.89-1.57; P = 0.245). Our findings suggest that there is no statistically significant association between patient sex and the efficacy of ICIs for ESCC patients. Importantly, we report, for the first time, a lack of survival benefit with the ICI plus chemotherapy regimen in the first-line setting compared to chemotherapy alone in female ESCC patients. Citation Format: Chaoqi Zhang, Peng Wu, Jingjing Liu, Dongyu Li, Nan Sun, Jie He. Sex-related disparity in immune checkpoint inhibitor benefit for patients with esophageal squamous cell carcinoma: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6118.

Impact of programmed cell death protein 1 inhibitor therapy on the survival of patients with advanced or recurrent uterine cancers: a meta-analysis.

No prior meta-analysis has investigated the impact of programmed cell death protein 1 (PD-1) inhibitor therapy on survival outcomes in patients with advanced or recurrent uterine cancers (including both corpus and cervical cancers). A comprehensive search of PubMed and Embase databases was conducted, covering the past 10 years (up to August 2023) and encompassing all clinical research related to uterine cancer. Five randomized controlled trials and one cohort study met the inclusion criteria and were included in the meta-analysis. Data on patient demographics, clinical characteristics, treatment regimens, and survival outcomes were extracted. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), as well as the relative risk of grade 3 or higher adverse events, were pooled using random-effects models. Patients receiving PD-1 inhibitors had better OS (HR, 0.65, 95% CI, 0.59-0.72; P<.001) and PFS (HR, 0.59, 95% CI, 0.49-0.70; P<.001) than those receiving variable non-PD-1 inhibitor therapies among 3452 uterine cancer patients. The leave-one-out meta-analysis of the HR of OS showed no individual study impact on the estimation of the overall effect size. Subgroup analysis revealed better OS in the PD-1 inhibitors use than the controls in cervical cancer (HR, 0.68, 95% CI, 0.59-0.79), endometrial cancer (HR, 0.62, 95% CI, 0.54-0.72), and pembrolizumab use (HR, 0.66, 95% CI, 0.57-0.75) subgroups. Patients with advanced cervical cancer, who had CPS > 1, receiving PD-1 inhibitors have statistically significant benefits in OS compared to controls (HR, 0.65, 95% CI, 0.53-0.80). The pooled HR for overall survival was 0.71 (95% CI, 0.60-0.82; P<.001) in patients who received PD-1 inhibitors as compared to those who did not receive PD-1 inhibitors in proficient mismatch repair (MMR) endometrial cancer patients. However, in deficient MMR patients, the HR was 0.30 (95% CI, 0.13-0.70). The relative risk of grade 3 or higher adverse events was not higher in the PD-1 inhibitor group (relative risk, 1.12, 95% CI, 0.98-1.27). Survival was significantly better using PD-1 inhibitor therapy than variable non-PD-1 inhibitor chemotherapies among patients with advanced or recurrent uterine cancers.

Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial

IntroductionExtensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC. MethodsRATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety. ResultsBetween July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range: 8.6–25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI): 0.61–0.93]; one-sided p = 0.0040; median: 15.5 [95% CI: 13.5–17.1] versus 13.5 mo [95% CI: 12.1–14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI: 0.52–0.78]; p < 0.0001; median: 4.7 [95% CI: 4.3–5.5] versus 4.3 mo [95% CI: 4.2–4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic. ConclusionsTislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC.

The Role of Systematic Lymphadenectomy in Low-Grade Serous Ovarian Cancer: A Systematic Review and Meta-Analysis.

To evaluate the role of systematic lymphadenectomy in low-grade serous ovarian cancer (LGSOC) and determine its impact on clinical outcomes in overall survival (OS) and disease-free survival (DFS) terms. A comprehensive, systematic computer literature search on PubMed was performed using the following Medical Subject Headings (MeSH) terms: "low grade serous ovarian cancer" AND/OR "lymphadenectomy" AND/OR "staging" AND/OR "ovarian cancer" AND/OR "cytoreduction". Separate searches were performed with MeSH terms on MEDLINE and EMBASE to extract all the relevant literature available. We included only patients with histologically confirmed LGSOC. Three studies were considered in the quantitative analysis. Systematic lymphadenectomy in LGSOC failed to provide a significant OS or PFS benefit in LGSOC when compared to no lymphadenectomy in the entire (all the stages) population (for OS: HR = 1.15, 95% CI [0.42, 3.18] I2 = 84% and for PFS: HR = 1.46, 95% CI [0.63, 3.41], I2 = 71%), nor did it in the subtype analysis regarding FIGO stages. For FIGO early-stage I-II LGSOC, the DFS data were pooled (HR = 1.48, 95% CI [0.58, 3.78], I2 = 75%). In patients with advanced-stage (FIGO II-IV), we also failed to prove survival benefit for lymphadenectomy in OS (HR = 1.74, 95% CI [0.87, 3.48], I2 = 11%) or DFS (HR = 1.48, 95% CI [0.58, 3.78], I2 = 75%) compared to no lymphadenectomy. More extensive prospective research is mandatory to understand the real impact of lymphadenectomy on survival in LGSOC. The existing literature does not provide strong evidence.

Treatment patterns and clinical outcomes of patients with resectable non–small cell lung cancer receiving neoadjuvant immunochemotherapy: A large-scale, multicenter, real-world study (NeoR-World)

BackgroundNeoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non–small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. MethodsNeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. ResultsA total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. ConclusionsThe study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.

Pathological response and tumor stroma immunogenic features predict long-term survival in non-small cell lung cancer after neoadjuvant chemotherapy.

Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined. We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS. Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17-0.77, p = 0.008) and DFS (HR = 0.59, 0.36-0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17-0.46, p < 0.001) and DFS (HR 0.44, 0.31-0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS. NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice.

Prognostic factors for anti-angiogenic treatment in patients with metastatic colorectal cancer: New insights for an old issue from a single institution experience.

206 Background: Anti-angiogenic drugs represent a cornerstone of metastatic colorectal cancer (mCRC) patients (pts) treatment. Currently, no prognostic/predictive biomarkers were validated to identify who is more likely to benefit from these agents. We performed at our Centre a retrospective research to assess potential prognostic/predictive factors in this population. Methods: We retrospectively collected laboratory, radiological and clinical data of mCRC pts receiving anti-angiogenic agents at the Medical Oncology Unit of Cagliari University Hospital (2018- 09/2023) in order to assess their correlation with overall survival (OS) and progression free survival (PFS) from the treatment start. Statistical analysis was performed with MedCalc (survival distribution: Kaplan-Meier; survival comparison: log-rank test; cut-off: ROC curves). Results: Globally, 32 mCRC pts were included in our research (19 male, 13 female; 12 RAS wild-type, 21 left-sided primary). 10 received anti-angiogenic drugs in the 1st-line, 12 in the 2nd-line (bevacizumab and aflibercept) and 10 in 1st-2nd line. Median OS was 34.8 months (m) (95%CI:24.7-41.6). We observed a statistically significant improve in OS (34.8 months [m] versus [vs] 8.2 m) in pts with higher monocyte count (&gt;0.3x103/μL; 95%CI 26.5-39.5 vs 95%CI 8.2-24.7, p=0.0103, HR 0.01), lower alcalin phosphatase (ALP; &lt;136 U/l; p=0.0001, HR=0.0001; 95%CI 12-39.5 vs 95% CI 8.2-10.4), lactate dehydrogenasis (LDH; &lt;365 U/l; p&lt;0,0001, HR=0.0000006; 95%CI 24.7-39.5 vs 95% CI 8.2-10.4) and platelet to lymphocyte ratio (PLR; ≤253; p&lt;0.0001, HR= 0.00000062; 95%CI 24.7-39.5 vs 95% CI 8.2-10.4). Median PFS was 14.9 m (95% CI 9.5-18.5). The same factors were significantly related to PFS, which was 18.3 m vs 2.7 m for higher monocyte count (95%CI 11.4-22.1 vs 95%CI 2.7-14, p=0.0386, HR=0.05), lower LDH (95%CI 11.4-22.1 vs 95%CI 2.7-8.9, p=0.0024, HR=0.004), lower PLR (95%CI 11.4-22.1 vs 95%CI 2.7-8.9, p=0.0024, HR=0.004) and 18.3 m vs 8.9 m for lower ALP (95%CI 11.4-23.3, p=0.0369, HR=0.04). Furthermore pts not developing bleeding during treatment showed a significant benefit in OS (39.5 m [95%CI 26.5-41.6] vs 8.2 m [95%CI 8.2-12], p&lt; 0.0001, HR 0.000001761) and improved PFS (17.9 m [95%CI 9.9-18.4] vs 2.4 m [95%CI 2.4-2.7]; p&lt;0.0001). Conclusions: Our findings showed a promising prognostic role of baseline monocytes, ALP, LDH and PLR and absence of bleeding occurrence in mCRC patients receiving anti-angiogenic drugs, even if in a limited population. Further larger prospective studies are encouraged for confirmation.

Characterization of outcomes and genomic alterations (GA) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA).

458 Background: Hepatobiliary cancers comprise a heterogeneous spectrum of invasive carcinomas involving the liver and bile ducts. Due to its rarity, the prognosis and clinical outcomes data are poorly understood. This study aims to provide insight into the response to therapeutic options and GA in patients (pts) with cHCC-CCA. Methods: We conducted a retrospective analysis of clinical outcomes data and GA at MD Anderson (MDA) from 2009 to 2023 in pts with cHCC-CCA. Pt characteristics were compared using Fisher’s exact test and Mann-Whitney U. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and the log-rank test. Results: 40 pts with cHCC-CCA were analyzed. Hepatitis B and C were the most common etiologies (Table). 25.0% had portal vein tumor thrombus and 72.0% had advanced disease (M1/N1) at diagnosis. Radiographic washout was seen in 55.9%. Elevation of CA19-9, AFP, and both was in 42.5, 57.5, and 30.0%. Cirrhosis at diagnosis was 35.0%. Pts who underwent surgery (n=10) had significant OS benefit (55.6 vs. 14.1 m, p&lt;0.001). Y90 (n=4)/radiation therapy (n=10) provided significant OS benefit in pts who did not undergo surgery (23.3 vs 10.9 m; p=0.012). 34 pts received 1st line systemic therapy: 10 pts received gemcitabine/cisplatin (GC) combined with immunotherapy (GCI): GC + nivolumab (n=5), durvalumab (n=3), or atezolizumab/bevacizumab (AB, n=2). GCI was compared to other regimens (OR, n=24) including chemotherapy alone (GC, FOLFIRI, FOLFOX), HCC-directed therapy alone (AB, lenvatinib, nivolumab), or chemotherapy plus lenvatinib or bevacizumab with mPFS of 7.0 vs. 2.9 m (p=0.014) showing significant PFS benefit. Pts who received GCI trended to better OS compared to OR (18.9 vs. 12.0 m, p=0.380). 2 pts treated with GC+AB had complete responses to date at 36.0 and 14.0 m. Of 31 pts who underwent GA testing, the 2 most frequent GAs were TP53 (38.7%) and TERT (35.5%) mutations. Neither impacted OS: TP53 15.8 vs. 17.6 m (p=0.746); TERT 9.8 vs. 23.3 m (p=0.355). Conclusions: GCI had survival benefit compared to OR in cHCC-CCA. Pts who present with early stage of disease should be evaluated early for surgical resection or maximize local therapy in the case of nonresectable disease to improve survival. [Table: see text]

Survival benefit and clinical characteristics of patients with metastatic colorectal cancer (mCRC) receiving pulmonary metastasectomy.

59 Background: The role of lung metastasectomy in mCRC remains a topic of particular controversy, being uncertain which patients benefit more from it and whether it leads to better survival outcomes. Our aim was to identify clinical and molecular differences and survival data in a cohort from a tertiary care hospital. Methods: We retrospectively analyzed 115 patients with lung metastases from colorectal cancer (CRC) in a tumor registry from 2015 to 2021, analyzing clinical and molecular characteristics, as well as overall survival (OS) data of patients who received lung metastasectomy versus patients who did not. Results: Among all patients, 36 (31.3%) received pulmonary metastases surgery. Patients undergoing metastases resection had more frequently ECOG 0 (51.4% vs 20.8%, p = 0.0011), resected primary tumor (100% vs 78.5%, p = 0.0026), metachronous metastatic disease (75% vs 46.8%, p = 0.0048) and a single metastatic location (79.4% vs 41%, p = 0.0002). In addition, none of them had BRAF mutation (0% vs 17.1%, p = 0.04); however, no statistically significant differences were found regarding KRAS, NRAS, PI3K, HER2 or presence of microsatellite instability (MSI). Patients who received lung metastasectomy had higher BMI (26.1 vs 24.4, p = 0.037) and lower mean levels of CEA (19.5 vs 142.9, p = 0.007), CA 19.9 (30.6 vs 244.9, p = 0.011) and LDH (159 vs 211.9, p = 0.018). We found an OS benefit in patients undergoing metastatic surgery (median not reached (NR) vs 41.4 months, HR for death 0.27, 95% CI, 0.14 - 0.53, p &lt; 0.000); a multivariate analysis confirmed that this benefit was independent from the characteristics mentioned above. The median progression-free survival (PFS) after metastases resection was 53.3 months. Conclusions: In our study, patients who were more likely to receive lung metastasectomy were those with ECOG 0, resected primary tumor, metachronous disseminated disease, a single metastatic location, native BRAF mutation status and low CEA, CA 19.9 and LDH levels, with a significant OS benefit associated.

Network meta-analysis of second line and beyond treatment options in metastatic clear cell renal cell carcinoma

IntroductionDeciding on the optimal second-line (2L) treatment for metastatic clear-cell renal cell carcinoma (ccRCC) remains challenging due to the limited information comparing each of the available options and the influence of the newly expanding first-line (1L) agents. Patients and MethodsWe identified phase II/III randomized controlled trials (RCTs) evaluating 2L treatments in metastatic ccRCC. This Network Meta-analysis (NMA) evaluates the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and severe adverse events (SAE). We used normal likelihood model to incorporate log hazard ratios (HRs), odds ratios (OR), and 95%-confidence-intervals (CI). Treatment p-scores were used for ranking. Data was analyzed in a fixed-effects model using the netmeta package in R v.1.5-0. ResultsAll therapies demonstrated some benefits over placebo. Lenvatinib + everolimus ranked first for OS (HR = 0.44; 95%CI = 0.24–0.82; p-score = 0.92), PFS (HR = 0.13; 95%CI = 0.07–0.24, p-score = 0.98), and ORR (OR = 35.95; 95%CI = 11.55–111.87; p-score = 0.93) compared to placebo, though with a higher SAE (OR = 5.27; p-score = 0.23). Cabozantinib ranked second for OS (HR = 0.57, p-score = 0.80), PFS (HR = 0.19; p-score = 0.86), and ORR (OR = 27.24, p-score = 0.84). Nivolumab was third for ORR (p-score = 0.79), fourth for OS (p-score = 0.69), fifth for PFS (p-score = 0.61), and last for SAE (p-score = 0.83). Lenvatinib monotherapy ranked worst SAE (OR = 5.89, p-score = 0.17) and third for OS and PFS. The latest drug, tivozanib, was sixth for PFS, OS, and ORR. The NMA matrix revealed no differential OS benefit between cabozantinib, lenvatinib + everolimus, and nivolumab. Other regimens had no significant OS benefit when compared to placebo. ConclusionBased on OS and PFS, the lenvtatinib + everolimus combination yielded superior, followed by cabozantinib and Lenvatinib monotherapies; all were limited by a worse SAE profile. Nivolumab and pazopanib had the lowest odds of SAEs.

Adjuvant chemotherapy on survival of patients with stage IB non‑small cell lung cancer: a comparison study with propensity score matching

BackgroundThis study aimed to investigate whether patients with stage IB NSCLC could benefit from adjuvant chemotherapy.MethodsIn the years 2010 to 2015, 1,829 NSCLC patients with stage IB disease were chosen from the SEER database. To equalize the baseline characteristics between the surgery plus adjuvant chemotherapy group (intervention) and the surgery alone group (control), propensity score matching (PSM) was used. The log-rank test plotted Kaplan–Meier survival curves to compare the overall survival (OS) and disease-specific survival (DSS). Cox proportional hazard regression was used to perform univariate and multivariate analysis on overall survival.ResultsOne hundred ninety-seven patients in each group with a mean follow-up period of 65.4 months were enrolled after PSM. A significant benefit in overall survival ([intervention vs. control] HR = 0.72; 95% CI: 0.54 to 0.94; P = 0.026) was detected in the intervention group before PSM. And there were significantly improved OS (HR = 0.63; 95% CI: 0.42 to 0.92; P = 0.036) and DSS (HR = 0.73; 95% CI: 0.52 to 0.95; P = 0.044) for the patients with visceral pleural invasion (VPI) in the intervention group compared with the control group. After PSM, the patients with VPI in the intervention group had better overall survival (HR = 0.69; 95% CI: 0.40 to 0.98; P = 0.048) than those in the control group. The Cox proportional hazard regression analysis showed that VPI (HR = 1.29; 95% CI: 1.11 to 1.54; P < 0.001) was also an independent prognostic factor.ConclusionStage IB NSCLC with VPI could benefit from adjuvant chemotherapy after R0 resection.

Neoadjuvant vs Adjuvant Chemoimmunotherapy for Stage II-IIIB Non-Small Cell Lung Cancer

BackgroundIn patients with resectable non-small cell lung cancer (NSCLC), recent trials demonstrate survival benefit of chemoimmunotherapy over chemotherapy alone in both the neoadjuvant and adjuvant settings. To date, there is no direct comparison between neoadjuvant and adjuvant protocols. We compared neoadjuvant vs adjuvant chemoimmunotherapy for resectable stage II-IIIB NSCLC. MethodsWe queried the National Cancer Database for patients who had undergone an operation for stage II-IIIB NSCLC and who had received neoadjuvant or adjuvant chemoimmunotherapy between 2015 and 2020. We used inverse probability weighting to adjust for confounding variables and used Kaplan-Meier survival curves and Cox regression to explore the relationship between treatment groups and overall survival (OS) at 3 years postoperatively. ResultsThe inverse probability-weighted cohort represented 2119 weighted patient cases (neoadjuvant, 1034; adjuvant, 1085). Kaplan-Meier analysis demonstrated a significant OS benefit for neoadjuvant chemoimmunotherapy compared with adjuvant chemoimmunotherapy in the weighted cohort (3-year OS: 77% [95% CI, 71%-83%] vs 68% [95% CI, 64%-72%]; P = .035). On adjusted Cox regression, neoadjuvant chemoimmunotherapy was associated with a significant OS benefit (hazard ratio, 0.70; 95% CI, 0.50-0.96; P = .027). Among patients for whom pathologic stage data were available, 25% of patients receiving neoadjuvant chemoimmunotherapy had a pathologic complete response, with an additional 32.5% being downstaged. ConclusionsNeoadjuvant chemoimmunotherapy confers a significant OS benefit over adjuvant chemoimmunotherapy for patients with resectable stage II-IIIB NSCLC. Although randomized trials are needed to confirm our findings, strong consideration should be given to administering neoadjuvant chemoimmunotherapy to patients who are predetermined to receive systemic treatment.

Postoperative Radiation Therapy for Thymic Carcinoma: An Analysis of the International Thymic Malignancy Interest Group/European Society of Thoracic Surgeons Database

IntroductionR0 resection and radiation therapy have been associated with improved overall survival (OS) in patients with thymic carcinoma (TC). Here, we analyzed which subgroups of patients derive the greatest benefit from postoperative radiation therapy (PORT). MethodsClinical, pathologic, treatment, and survival information of 462 patients with TC from the International Thymic Malignancy Interest Group/European Society of Thoracic Surgeons database were analyzed. Variables included age, sex, continent of treatment, paraneoplastic syndrome, carcinoma subtype, tumor size, pathologic Masaoka stage, resection status, and use of chemotherapy. OS was the primary end point using the Kaplan-Meier method. Time to recurrence (TTR) was the secondary end point using a competing risk analysis. A 3-month landmark analysis was performed. ResultsPORT was associated with a significant OS benefit (5-y OS 68% versus 53%, p = 0.002). In patients with R0 resection, PORT was associated with increased OS for advanced (stages III–IV, p = 0.04), but not early (stages I–II, p = 0.14) stage TC. In patients with an R1/2 resection of advanced-stage TC, PORT was associated with significantly longer OS (5-y OS 53% versus 38%; p < 0.001). Subset analyses did not reveal clear associations of PORT with TTR. On multivariable analysis, lower pathologic stage, PORT, and R0 resection status were associated with an OS benefit, whereas only higher age and lower pathologic stage had an association with longer TTR. ConclusionsIn the largest individual patient data set on patients with TC reported to date, PORT was associated with a meaningful OS benefit in patients with advanced-stage TC after an R0 or R1/2 resection.

Adjuvant chemotherapy in patients with clinically node-negative but pathologically node-positive rectal cancer in the Netherlands: A retrospective analysis

IntroductionAccurate clinical staging of rectal cancer is hampered by suboptimal sensitivity of MRI in the detection of regional lymph node metastases. Consequently, some patients may be understaged and have been withheld neoadjuvant (chemo)radiotherapy in retrospect. Although Dutch guidelines do not advocate adjuvant chemotherapy (ACT) in rectal cancer, some of these clinically understaged patients receive ACT according to local policy. We aim to assess the benefit of ACT in these patients. MethodsPopulation-based data from patients with clinically node-negative (cN0) but pathologically node-positive (pN+) rectal cancer that underwent total mesorectal excision (TME) without neoadjuvant treatment between 2008 and 2018 were obtained from the Netherlands Cancer Registry. Missing data were handled by multiple imputation. Stabilised inverse probability treatment weighting (sIPTW) was used to balance clinical characteristics. Overall survival (OS) was compared in ACT and non-ACT patients. ResultsOf 34,724 patients, 13,861 had cN0 disease of whom 3016 were pN+ (21.8%). 1466 (48.6%) of these patients underwent upfront TME and were included. Median follow-up was 84 months (95% confidence interval [CI] 76–97) versus 79 months (95% CI 77–81) in patients that did (n = 290, 19.8%) and did not (n = 1176, 80.2%) receive ACT, respectively. After sIPTW adjustment, ACT was associated with improved OS (hazard ratio 0.70; 95% CI 0.49–0.99; p = 0.04). The estimated 5-year OS rate was 74.2% versus 65.3%, respectively. ConclusionIn this population-based cohort of patients with cN0 but pN+ rectal cancer who underwent upfront TME, ACT was associated with a significant OS benefit. These data support to discuss ACT in this population.

Prognostic significance of lymph nodes assessment during pulmonary metastasectomy: a systematic review and meta-analysis.

Lung metastasectomy is an accepted treatment modality worldwide. Whether the addition of lymph node dissection to the procedure is useful remains, however, unknown. We performed a systematic review of the literature analyzing MEDLINE, Embase, until 31st October 2021. We included all studies which met the inclusion criteria aiming to determine if the addition of lymph node tissue dissection/sampling to lung metastasectomy offers survival benefits when compared to patients who do receive lymph node tissue dissection. Secondary outcomes were 3- and 5-year overall survival (OS) and disease-free survival (DFS). Each study was assessed for risk of bias. The data collected from the included studies were pooled using reconstruction of individual-level patient data and pooling of reported 5-year odds ratios (ORs). Interstudy heterogeneity was estimated with visual inspection of forest plots and calculation of the I2 inconsistency statistic. We found 11 eligible studies that included a total of 3,310 patients. The most common primary tumor type was colorectal cancer (1,740 patients) and the most commonly performed operative procedure was wedge resection (57%) followed by lobectomy (39%). When resection status was reported, R0 resection was achieved in 90% of the cases. Nine studies did not show a statistically significant effect of lymph nodes dissection or sampling on the 5-year OS with a pooled hazard ratio (HR) of 0.94 [95% confidence interval (CI): 0.82, 1.08; I2=26%; 95% prediction interval (PI): 0.70, 1.24]. Regarding DFS, the pooled HR 0.60 (95% CI: 0.44, 0.80; I2=31%; 95% PI: 0.12, 2.09). The addition of lymph node tissue dissection during lung metastasectomy was not associated with a significant benefit in OS and showed a slight tendency towards a better DFS.

Contralateral prophylactic mastectomy for unilateral breast cancer in Chinese female population: a retrospective cohort study.

Due to differences in socioeconomic and cultural backgrounds, the characteristics and prognosis of Asian female patients choosing contralateral prophylactic mastectomy (CPM) are likely to be different from Western patients. To fill the research gap of CPM in Asian populations, this study aims to explore the application trend, survival benefits, decision-making factors, and satisfaction of CPM based on the Chinese patients undergoing CPM. The 0-III stage unilateral breast cancer (UBC) patients who received breast surgery in the Chinese PLA General Hospital from 2005 to 2017 were selected. The surgical procedures included simple mastectomy (SM), nipple-sparing mastectomy (NSM), breast conserving surgery (BCS), and CPM. Cox proportional regression analyses and Kaplan-Meier (KM) curve were performed to compare the overall survival (OS) and disease-free survival (DFS) rates between CPM group and unilateral mastectomy (UM) group. Proportional propensity score matching (PSM) with a 1:1 ratio was used to match the two groups and secondary survival analysis was performed. Logistic regression models were used to test predictive factors related to patients' CPM surgical decision-making. Four thousand two hundred and seventy-six patients were included in the study, with 73 patients receiving CPM, 3,567 receiving SM, 151 receiving NSM, and 485 receiving BCS. CPM surgery was first used in 2007, with a peak application rate of 3.02% in 2016. Three thousand seven hundred and ninety-one patients were included in the survival analysis, with a median follow-up time of 66.60 months. Compared to UM patients, neither the KM survival curve nor Cox regression hazard analyses of CPM showed better OS (P=0.963; P=0.834). After PSM, CPM also did not exhibit significant survival benefits in OS (P=0.335) and DFS (P=0.409). The logistic regression analyses showed that NSM surgery and lower tumor-node-metastasis (TNM) stage were independent factors to promote the CPM decision-making of patients. The CPM group showed high overall satisfaction (84.9%) and relatively low appearance satisfaction (69.9%). CPM was practiced for the first time since 2007 in our hospital. CPM does not provide any OS and DFS benefits compared to UM and the appearance satisfaction procedure was relatively low. Therefore, clinicians should fully communicate with patients before surgery and be more cautious in giving CPM recommendations.

Updated Results from a Matching-Adjusted Indirect Comparison of Efficacy Outcomes for Isatuximab Plus Pomalidomide and Dexamethasone Versus Daratumumab Plus Pomalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma

Introduction: Findings from a previously conducted matching-adjusted indirect comparison (MAIC) between isatuximab plus pomalidomide and dexamethasone (IsaPd) and daratumumab plus pomalidomide and dexamethasone (DaraPd) among relapsed and/or refractory multiple myeloma (RRMM) patients receiving at least two prior lines of therapy (LoT) including lenalidomide and a proteasome inhibitor (PI) demonstrated a significantly better overall survival (OS) and a positive trend for progression-free survival (PFS), overall response rate (ORR), and very good partial response or better (≥VGPR) rates with IsaPd than that with DaraPd, with a similar safety profile for both treatments [Leleu X et al, Value in Health 2022;25(1):S39]. The present study used longer follow-up data from the phase 3 ICARIA trial (NCT02990338) to update the previous MAIC, evaluating the comparative efficacy of IsaPd versus DaraPd. Methods: A MAIC was performed with the latest available individual patient-level data (IPD) from the ICARIA trial (IsaPd arm, n = 154; Pd arm, n = 153), data cutoff of March 14, 2022, and aggregate data from study publications of the phase 3 APOLLO trial (DaraPd arm, n = 151; Pd arm, n = 153, NCT03180736) [Dimopoulos MA, et al. Blood 2022;140 (Suppl 1):7272-7274; Dimopoulos MA, et al. Lancet Oncol. 2021;22(6):801-812; Dimopoulos MA, et al. Blood 2020;136(Suppl 1):5-6]. To match patients with APOLLO, patients in ICARIA who did not meet the inclusion criteria of APOLLO were excluded. In APOLLO, 11% patients received only one prior LoT. As patients with one prior LoT were not enrolled in ICARIA, it was not feasible to match on this factor; however, the treatment effect of DaraPd versus Pd on PFS among these patients was similar to patients in APOLLO with ≥2 prior LoTs. Therefore, this difference in study populations is unlikely to bias the MAIC. Remaining patients in ICARIA were then weighted using standardized MAIC weights (mean value = 1.0) generated using the method of moments, with active treatment and control arms matched separately to ensure any residual imbalances between active and control arms in APOLLO were replicated in the matched ICARIA sample. Anchored MAICs for the hazard ratio (HR) for OS and PFS, odds ratio (OR) for ORR, and ≥VGPR for IsaPd versus DaraPd were calculated using the Bucher method [Bucher HC, et al. J Clin Epidemiol. 1997;50(6):683-691]. Results: MAIC weighting was able to match all characteristics included in the matching algorithm, with standardized mean difference (SMDs) &amp;lt;0.0001 after weighting. The effective sample size after weighting was 28.1 for IsaPd and 43.1 for Pd. Based on an anchored MAIC, OS was significantly better with IsaPd versus DaraPd (HR [95% CI]: 0.49 [0.24-0.98]; p = 0.04) (Figure 1). A numerical trend in favor of IsaPd versus DaraPd was observed for PFS, ORR, and ≥VGPR, although the differences were statistically non-significant (Table 1). Conclusions: This MAIC analysis demonstrated a significant benefit in OS and a positive trend in the improvement of PFS, ORR, and ≥VGPR in favor of IsaPd compared with DaraPd. These findings were consistent with the previous MAIC with a longer follow-up data (present analysis used a maximum follow-up of 4.5 years of OS data from both trials, whereas the previous analysis used a follow-up of 3 years from ICARIA and unknown from APOLLO), which highlights the therapeutic potential of IsaPd in RRMM, particularly for patients who become refractory to lenalidomide and a PI.

Differences in Molecular Alterations and Clinical Outcomes By Ethnicity for Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents and Venetoclax

Introduction: Clinical outcomes for non-Hispanic Black and Hispanic patients with acute myeloid leukemia (AML) have been reported to be worse compared with non-Hispanic white patients despite increasing therapy options. Socioeconomic factors play a large role in causing these disparities. However, whether specific molecular alterations are associated with a particular ethnic group is understudied in adult populations. Prior studies either involve the pediatric population or focus on a few selected ethnic groups. Our primary objective is to determine whether particular molecular alterations associated with specific ethnic groups are associated with higher mortality. Methodology: Retrospective data was collected for 142 patients with AML diagnosed from July 2018 to December 2022 and treated in the Northwell Health system with a hypomethylating agent (HMA) and venetoclax. Demographic information was manually obtained from the electronic medical record (EMR) and ethnicity was categorized as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, Asian, or other/multiracial. Overall survival (OS) was calculated as the time difference between date of definitive diagnosis prior to starting venetoclax to death or date of last contact. Molecular alterations were detected by next-generation sequencing (NGS) testing. We looked at the presence of TP53, TET2, RUNX1, NPM1, FLT3-ITD, IDH1, IDH2, and several other mutations/deletions. Kaplan-Meier analysis with log-rank (Mantel-Cox) testing was used to compare overall survival between ethnic groups. Results: Of 142 patients, 87 (61%) were NHW, 23 (16%) were NHB, 7 (5%) were Asian, 10 (7%) were Hispanic, and 15 (11%) were other/multiracial. Median age was 77 years. The most common molecular alterations were TP53 mutations/deletions (25%) for the NHW group, TET2 (27%) for the NHB group, NPM1 without FLT3-ITD (43%) for the Asian group, ASXL1 and RUNX1 (both 40%) for the Hispanic group, and RUNX1 (40%) in the other/multiracial group. The NHB group had a similar incidence of TP53 mutations/deletions (21%) as the NHW group did. Median number of cycles of HMA and venetoclax tolerated was 2 for NHW, 3 for NHB, 5 for Asians, 3 for Hispanics, and 4 for other/multiracial. Kaplan-Meier analysis comparing all groups simultaneously did not show a significant difference in OS, X 2 (4, N = 142) = 5.37, p = 0.25. Individual comparisons between the NHB (X 2 (1, N = 110) = 0.61, p = .43), Hispanic (X 2 (1, N = 97) = 0.27, p = .61), and other/multiracial (X 2 (1, N = 102) = 0.90, p = .34) groups with the NHW group did not show any significant difference either. Asians had better OS when compared individually with the NHW group (X 2 (1, N = 94) = 4.29, p = .038). However, no significant difference was observed when OS for Asians was compared with OS for any other group. Conclusions: In this cohort of patients, the only significant OS benefit was in favor of Asians compared with NHW group. Based on molecular alterations, this may reflect the increased incidence of NPM1 mutations without FLT3-ITD mutations and decreased incidence of TP53 mutations in Asian patients. Additionally, adverse molecular alterations (TP53, RUNX1) were increased in the non-Asian groups. Asians were able to tolerate more cycles of HMA and venetoclax than any other group. Though prior studies suggested that Asians have molecular alterations with favorable risk, the sample size in this study for the Asian group (N = 7) was too small to make any definitive conclusions. Future studies should build on these findings.

Diffuse Large B-Cell Lymphoma CNS Relapse Prophylaxis with Intrathecal or High-Dose Intravenous Methotrexate

Introduction: Central nervous system (CNS) relapse is a relatively infrequent but often fatal complication of the most common subtype of non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL). Median overall survival (OS) after DLBCL relapse in the CNS is about 4 months. Despite identifying patients at high risk of developing CNS relapse using the CNS international prognostic index (CNS-IPI) score, it has been difficult to validate any specific strategy. Various chemotherapies and administration methods have been tested. Thus far, only the addition of rituximab to chemotherapy has yielded significant results. Our objective is to determine if administering prophylactic chemotherapy is efficacious in preventing DLBCL relapse in the CNS. Methodology: We collected retrospective data for patients with newly diagnosed DLBCL treated with rituximab and anthracycline-based chemotherapy from 2010 to 2020 in the Northwell Health system to determine the efficacy of CNS prophylaxis. Patients with CNS disease at diagnosis, primary testicular lymphoma, primary mediastinal large B-cell lymphoma, and HIV-associated lymphoma were excluded from this study. CNS prophylaxis was defined as receiving at least two doses of prophylactic chemotherapy, whether intravenous or intrathecal. Follow up for at least one year after diagnosis was required for inclusion. Overall survival (OS) was defined as the time difference between the date of definitive diagnosis to death or last date of contact. Other potential prognostic factors including double hit status and cell of origin, germinal center B-cell (GCB) vs. non-germinal center B-cell (non-GCB), were also evaluated. Pearson's chi-square analysis was used to compare the rate of DLBCL relapse in the CNS based on whether patients received CNS prophylaxis. Low risk was defined as CNS-IPI score 0 to 3 and high risk as CNS-IPI score 4 to 6. Kaplan-Meier analysis with log-rank (Mantel-Cox) testing was used to determine if any significant OS benefit was observed for the low and high-risk groups based on CNS-IPI score. Results: Of the 437 charts reviewed, 127 were eligible for inclusion. Most patients were male (56.7%). Median age was 69 years and median Eastern Cooperative Oncology Group (ECOG) performance status was 1. Most cases were non-GCB (44.9%, as 25% of cases were missing data) and not double hit (85%). Of the 35 patients at high risk for CNS relapse, 27 (77%) received prophylaxis. Intrathecal methotrexate (IT MTX) was given to 26 patients (96%) and high dose intravenous methotrexate (HD MTX) was given to 1 patient. CNS relapse occurred in 6 patients, of which 5 had a low-risk CNS-IPI score. One of the five patients in the low-risk group and the one patient in the high-risk group that had CNS relapse received prophylaxis. No significant difference in overall relapse rates were observed based on whether prophylaxis was given, X 2 (1, N = 127) = 0.30, p = .59. Kaplan-Meier analysis showed no difference in OS after stratification of patients by CNS-IPI score into the high-risk ( p = .50) and low-risk ( p = .24) groups. HD MTX was not administered frequently enough to determine its efficacy. Neither cell of origin (X 2 (1, N = 95) = 2.95, p = .086) nor double hit status (X 2 (1, N = 127) = 1.512, p = .22) had any significant effect on OS. Conclusions: We did not observe any clear benefit for administering IT MTX to prevent DLBCL relapse in the CNS. Most of the CNS relapse events occurred in the low-risk group, even though 8 patients in the high-risk group did not receive any CNS prophylaxis. This study did not have sufficient power to make a definitive conclusion. As CNS relapse is a rare event, a much larger sample size is required to determine the true efficacy of CNS prophylaxis. Non-GCB cell origin and positive double hit status are not included in the CNS-IPI score but their potential association with risk of DLBCL relapse in the CNS is understudied. Future studies should build upon these findings.