Improvement In Disease-free Survival Research Articles

Systematic review on the efficacy and safety of ixabepilone-based chemotherapy regimen in triple-negative breast cancer

Context: Triple-negative breast cancer (TNBC) has poor prognosis, high mortality, and recurrence rates. Ixabepilone or ixempra could be a promising agent for TNBC, especially in the taxane- and/or anthracycline-resistant population. Aims: To evaluate the efficacy and safety of ixabepilone-based chemotherapy compared to ixabepilone-free chemotherapy in TNBC patients. Methods: This review followed the preferred reporting items for systematic reviews and meta-analysis guidelines. The eligibility criteria included randomized control trials (RCTs) in 2013-2023 comparing ixabepilone-based with ixabepilone-free chemotherapy regimen in TNBC. Results: This study identified four eligible RCTs. One study showed that patients treated with ixabepilone had a significant improvement in disease-free survival, had a better response, and a lower risk of disease recurrence compared to those treated with taxane-based regimen. However, two studies showed no differences in terms of overall survival (OS), disease-free survival, and pathological complete responses rates in both treatment arms. Ixabepilone addition to capecitabine significantly prolonged progression-free survival and objective response rate in TNBC patients, but did not significantly improve OS (n = 1). Conclusions: The effectiveness and safety of ixabepilone-based chemotherapy versus ixabepilone-free treatment for triple-negative breast cancer (TNBC) patients vary among studies. More research is needed to better understand the effectiveness and safety of ixabepilone-based chemotherapy versus ixabepilone-free treatment in TNBC patients.

Shifting Paradigms in TNBC Treatment: Emerging Alternatives to Capecitabine in the Post-Neoadjuvant Setting

Background: Triple-negative breast cancer (TNBC) remains a clinically challenging subtype due to its aggressive nature and limited treatment options post-neoadjuvant failure. Historically, capecitabine has been the cornerstone of adjuvant therapy for TNBC patients not achieving a pathological complete response (pCR). However, the integration of new modalities such as immunotherapy and PARP inhibitors has prompted a re-evaluation of traditional post-neoadjuvant approaches. Methods: This review synthesizes data from pivotal clinical trials and meta-analyses to evaluate the efficacy of emerging therapies in the post-neoadjuvant setting. We focus on the role of immune checkpoint inhibitors (ICIs), PARP inhibitors (PARPis), and antibody-drug conjugates (ADCs) alongside or in place of capecitabine in TNBC treatment paradigms. Results: The addition of ICIs like pembrolizumab to neoadjuvant regimens has shown increased pCR rates and improved event-free survival, posing new questions about optimal post-neoadjuvant therapies. Similarly, PARPis have demonstrated efficacy in BRCA-mutated TNBC populations, with significant improvements in disease-free survival (DFS) and overall survival (OS). Emerging studies on ADCs further complicate the adjuvant landscape, offering potentially efficacious alternatives to capecitabine, especially in patients with residual disease after neoadjuvant therapy. Discussion: The challenge remains to integrate these new treatments into clinical practice effectively, considering factors such as drug resistance, patient-specific characteristics, and socio-economic barriers. This review discusses the implications of these therapies and suggests a future direction focused on personalized medicine approaches in TNBC. Conclusions: As the treatment landscape for TNBC evolves, the role of capecitabine is being critically examined. While it remains a viable option for certain patient groups, the introduction of ICIs, PARPis, and ADCs offers promising alternatives that could redefine adjuvant therapy standards. Ongoing and future trials will be pivotal in determining the optimal therapeutic strategies for TNBC patients with residual disease post-neoadjuvant therapy.

Reduced intensity conditioning regimen of fludarabine, busulfan, ATG based haploidentical stem cell transplantation for older or unfit patients.

Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of anti-thymocyte globulin (ATG) based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG-based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in older or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG-based haploidentical HSCT. We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30mg/m²/kg 6 days combined with busulfan 3.2mg/kg 2 days (Bu2) or 3 days (Bu3). ATG-Fresenius (ATG-F) was administered 10mg/kg in total, ATG-thymoglobulin (ATG-T) was administered 6mg/kg in total. The median age of patients in the entire cohort was 60 (32-67) years with a median follow-up of 496 (83-2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. A total of 32 patients underwent Bu2 RIC haplo-HSCT and 31 patients were treated with Bu3 RIC haplo-HSCT. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8 - 85.1%) and 61.4% (95% CI, 48.8 - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8% (95% CI, 4.8 - 19.6%) and 9.7% (95% CI, 0.0 - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9 - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5 - 33.7%) and 11.6% (95% CI, 2.2 - 21.9%) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5-85.3%) in Bu2 and 85.5%(95% CI:73.0-100%) in Bu3 group respectively(P = 0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0-74.8%) in Bu2 and 72.6% (95% CI:55.5-95.5%) in Bu3 group respectively (P = 0.045). The 2-year IR of Bu2group was significantly higher than Bu3group(P = 0.045). However, the2-year NRM were not significantly different between Bu2 and Bu3 group(P > 0.05). In multivariable analysis, RIC regimen of Bu3 had superior OS and DFS than Bu2 group respectively [HR 0.42, 95% CI 0.18-0.98; P = 0.044; HR 0.34, 95% CI 0.14-0.86; P = 0.022]. Besides, RIC regimen of Bu3 had lower IR than Bu2 group [HR 0.34, 95% CI 0.13-0.89; P = 0.029]. The RIC regimen of ATG-based haploidentical HSCT is a safe and effective treatment option for patients who are older or have poor functional status. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in OS and DFS, thus providing more favorable post-transplantation clinical outcomes.

Molecular residual disease (MRD) analysis from the ADAURA trial of adjuvant (adj) osimertinib in patients (pts) with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC).

8005 Background: Osimertinib (osi) is a third-generation, central nervous system-active EGFR-TKI, that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations. Adj osi (3 years [yrs]) is recommended for resected EGFRm stage IB–IIIA NSCLC, based on significant improvements in disease-free survival (DFS) and overall survival (OS) in the Phase III ADAURA study (NCT02511106). A trend towards an increased DFS event rate beyond 3 yrs suggests some pts may benefit from longer adj osi treatment (tx). We explored if plasma ctDNA-based, tumor-informed MRD could predict disease recurrence. Methods: Eligible pts (≥18 yrs [≥20 in Japan/Taiwan], WHO PS 0/1 with completely resected EGFRm [Ex19del/L858R] stage IB, II or IIIA [AJCC 7th edition] NSCLC) were randomized 1:1 to osi 80 mg once daily or placebo (pbo) until disease recurrence, tx completion (up to 3 yrs), or a discontinuation criterion was met. Personalized MRD panels (RaDaR, NeoGenomics) were used, comprised of ≤50 tumor-specific variants, based on whole exome sequencing of resected tumor tissue (variants identified in germline DNA removed). Plasma sample collection: baseline (BL; at randomization surgery and adj Ctx, if received), on tx (every 12 weeks [wks]), tx discontinuation, and post-tx completion (wk 12, wk 24, then every 24 wks until 5 yrs). Plasma samples were analyzed for detection of ctDNA (MRD+). Molecular recurrence or DFS (MRD/DFS) was defined as time from randomization to post-BL MRD+, disease recurrence, or death and was compared across arms. DFS was investigator-assessed. Results: Of 682 pts randomized, 245 (36%) had samples required to produce MRD panels, which were evaluable for 220 (32%) pts across both arms. In the osi vs pbo arms, 5/112 (4%) vs 13/108 (12%) pts were MRD+ at BL; 4/5 pts became MRD– during osi tx vs 0/13 pts on pbo. On tx, MRD detection had clinical sensitivity of 65% (62 MRD+/96 DFS+), specificity of 95% (118 MRD–/124 DFS–) and preceded a DFS event by a median (95% CI) of 4.7 (2.2, 5.6) months (mos) across both arms. Median follow-up time from randomization was 44.2 (95% CI 42.4, 49.1) and 19.1 (95% CI 11.1, 28.3) mos for osi and pbo arms, respectively. Overall, 86% (95% CI 78, 92) vs 36% (95% CI 27, 45) pts in the osi vs pbo arms were MRD/DFS event free at 36 mos (HR: 0.23; 95% CI 0.15, 0.36). MRD/DFS events in the osi arm were detected at any time post-BL in 28 (25%) pts, of whom 19/28 (68%) had events post-adj osi. Most (11/19 [58%]) MRD/DFS events detected occurred within 12 mos of osi tx completion. Conclusions: MRD+ preceded DFS events in most pts with a median lead time of 4.7 mos across both arms. MRD– was maintained for most pts during adj osi tx with the majority of MRD/DFS events occurring after osi tx completion. MRD detection could potentially identify a subset of pts likely to benefit from longer adj osi. Clinical trial information: NCT02511106 .

Tislelizumab plus tyrosine kinase inhibitor versus active surveillance in patients with ablated high-risk hepatocellular carcinoma: An open-label, parallel controlled, prospective cohort study.

e16238 Background: In IMbrave050, adjuvant atezolizumab plus bevacizumab demonstrated improvement in recurrence-free survival vs active surveillance in patients at high risk of hepatocellular carcinoma (HCC) recurrence following resection or ablation with curative intent. However, there is limited study on programmed cell death protein 1 (PD-1) inhibitor plus tyrosine kinase inhibitor (TKI) as postoperative adjuvant therapy for HCC. We aimed to assess the safety and efficacy of tislelizumab (a PD-1 inhibitor) plus TKI as adjuvant therapy versus active surveillance in patients at high risk of HCC recurrence after curative ablation. Methods: This study enrolled patients with HCC at high risk of recurrence following curative ablation. Patients were paralleled to Arm A (tislelizumab plus TKI) or Arm B (active surveillance). Patients in Arm A received tislelizumab (200 mg, IV, q3w) plus TKI for three months (4 cycles) following curative ablation, while those patients in Arm B underwent active surveillance. Primary endpoints were safety and tumor recurrence rate. Secondary endpoint was disease free survival (DFS). Exploratory endpoints included biomarkers related to the recurrence. Results: A total of 48 patients were enrolled with a median follow-up time of 283 days (IQR: 123-460 days, clinical cutoff date: 1 Jan 2024). Nine patients (37.5%) reported at least one adverse event of any degree in Arm A and three patients (12.5%) reported in arm B, most of which were mild. Only one patient in arm A experienced a grade 3 treatment-related adverse event, which improved after administration of symptomatic treatment. The recurrence rate of patients in arm A was 20.83%, which was significantly lower than the 58.3% in arm B (OR = 0.188 [95% CI: 0.052 - 0.674], P = 0.017). Four cycles of adjuvant tislelizumab plus TKI therapy was associated with significantly improved DFS (median, not evaluable [NE]) compared with active surveillance (median, 188 days [95% CI: 78.4 - 297.6 days]; HR = 0.396 [95% CI: 0161 - 0.973], P = 0.044). The absence of tislelizumab treatment (OR = 4.823 [95% CI: 1.091 - 21.329], P = 0.038) and multiple tumor lesions (OR = 7.651 [95% CI: 1.270 - 46.114], P = 0.026) were risk factors for recurrence of HCC after curative ablation. Conclusions: The safety of tislelizumab plus TKI combination therapy were generally manageable. Statistically significant and clinically meaningful improvement in tumor recurrence rate and DFS were seen in patients receiving combination therapy vs active surveillance. This study was a positive attempt to undergo short-course PD-1 inhibitor plus TKI combination therapy in patients with HCC at high risk of recurrence following curative ablation, showing promising efficacy in preventing HCC recurrence. Clinical trial information: NCT06059885 .

Abstract A008: Racial differences in characteristics and outcomes of adjuvant nivolumab for muscle-invasive urothelial carcinoma (MIUC) in the real-world setting

Abstract Objectives: Historically, African-American/Black patients with bladder cancer have worse clinical outcomes compared with White/Caucasian patients. In the CheckMate 274 trial, nivolumab demonstrated a significant improvement in disease-free survival compared with placebo among patients with MIUC at high risk of recurrence following radical surgery; however, African-American/Black patients were underrepresented (< 1%). The objective of this analysis was to describe the characteristics and outcomes of MIUC patients treated with adjuvant nivolumab across different racial subgroups in a real-world setting. Methods: This US retrospective medical chart review included African-American/Black and White/Caucasian patients with MIUC treated with adjuvant nivolumab following radical resection between 01-Sep-2021 and 10-Sep-2022. Patient characteristics and outcomes were abstracted from the medical charts by treating oncologists. Patient characteristics and landmark survival estimates based on Kaplan-Meier analyses were summarized descriptively. Results: The analysis included 223 patients (African-American/Black: 62; White/Caucasian: 161). A numerically higher proportion of African-American/Black vs White/Caucasian patients, respectively, was male (74.2% vs 66.5%), less than 60 years old (27.4% vs 20.5%), unemployed (16.1% vs 5.6%), and had Medicaid at therapy initiation (14.5% vs 6.2%). Similar proportions in both groups had ECOG performance status 0-1 (82.3% vs 82.6%), received neoadjuvant therapy (58.1% vs 56.5%), and completed adjuvant therapy (67.7% vs 66.5%). The median follow-up time (12.5 months vs 13.1 months) and median duration of adjuvant therapy (11.0 months vs 11.3 months) were comparable. Similar estimates were observed for 12-month overall survival (96.7% vs 91.4%), 12-month disease-free survival (88.3% vs 88.4%), and 12-month distant metastasis-free survival (88.3% vs 88.4%). Conclusions: Despite higher rates of socio-economic risk factors among African-American/Black patients, this real-world study suggests similar effectiveness of adjuvant nivolumab among MIUC patients across African-American/Black and White/Caucasian patient populations. Citation Format: Regina Barragan-Carrillo, Alexander Chehrazi-Raffle, Bruce Feinberg, William S. John, Taavy A. Miller, Sarah Lucht, Prathamesh Pathak, Emily Bland, Sarah Gordon, JaLyna Laney, Andrew J. Klink, Hedyeh Ebrahimi, Nisha Singh, Carmelo Alonso, Miraj Patel, Lisa Rosenblatt, Xin Yin. Racial differences in characteristics and outcomes of adjuvant nivolumab for muscle-invasive urothelial carcinoma (MIUC) in the real-world setting [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A008.

Preferences of physicians for treatment-related toxicity vs. recurrence in melanoma (GERMELATOX-A): the doctors’ perspective

IntroductionAdjuvant treatment with immune checkpoint inhibitors, such as PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT), has shown a significant improvement in disease-free survival (DFS) for high-risk melanoma patients. However, due to specific side effects, the choice of treatment is often influenced by the risk of toxicity. Therefore, the role of physicians in treatment decisions of patients is crucial. This study investigated for the first time in a multicenter setting the attitudes and preferences of dermatooncologists in Germany and Switzerland regarding adjuvant treatment with (c)ICI and TT.MethodsIn the GERMELATOX-A study, 108 physicians (median age: 32 yrs, 67.6% female) from 11 skin cancer centers were surveyed to rate typical side effect scenarios of (c)ICI and TT treatments and then compared to patients’ ratings evaluated in a previous analysis from the same centers. The scenarios described mild-to-moderate or severe toxicity and included melanoma relapse leading to death. The physicians were asked about the level of side effects they would tolerate in exchange for a reduction in melanoma relapse and an increase in survival at 5 years.ResultsThe preferences of physicians and patients revealed significant differences regarding adjuvant melanoma treatment with (c)ICI and TT (p < 0.05). Compared to patients, physicians tend to value a melanoma relapse less severe, according to a visual analog scale. They were also less threatened by all scenarios of side effects during adjuvant treatment with (c)ICI or TT, compared to patients. Physicians required lower risk reductions for disease-free survival (DFS) and overall survival (OS) for both ICI and TT and their drug-related side effects to accept these treatments. In case of severe side effects, physicians required similar 5-year DFS rates for ICI and TT (60–65%), while patients needed a 15% improvement of 5-year DFS for ICI compared to TT (80%/65%). For survival, physicians expected an OS improvement of + 10% for all three treatment modalities, whereas patients required a higher increase: + 18–22% for ICI and + 15% for TT.ConclusionOur study highlights the importance of understanding the patient’s perspective and a potential difference to the doctor’s view when making decisions about adjuvant melanoma treatment with (c)ICI and TT, especially as these treatments are increasingly being implemented in earlier stages.

Abstract PO1-17-08: Post-approval treatment patterns and tolerability of neratinib in HER2+ early-stage breast cancer

Abstract Background: While the approval status for neratinib in HER2+ early-stage breast cancer (EBC) allows its use following any trastuzumab-based therapy, the phase 3 ExteNET trial (NCT00878709), which yielded an improvement in disease-free survival, was conducted when single-agent adjuvant trastuzumab was standard of care (SOC) and before approvals of adjuvant pertuzumab + trastuzumab (FDA-approved 2017) or trastuzumab emtansine (T-DM1; FDA-approved 2019). Given recent changes in SOC for HER2+ EBC, health care professionals may seek contemporary and real-world information regarding treatment patterns and tolerability of neratinib. Methods: A literature review was performed to identify studies that characterized trends in use of extended adjuvant neratinib in HER2+ EBC. Due to differences in study design (interventional, observational, claims data) and populations studied, a descriptive summary of data is presented in lieu of statistical cross-study comparisons. Results: Following FDA approval of neratinib in HER2+ EBC in 2017, five studies have reported treatment patterns of extended adjuvant neratinib in a clinical trial or real-world setting; three studies included safety data (Table 1). In the phase 2 CONTROL trial (NCT02400476; N=563; 2015–2021), approx. 82%, 17%, and 1% of neratinib-treated pts received prior adjuvant trastuzumab, pertuzumab, or T-DM1, respectively, and prior neoadjuvant/adjuvant pertuzumab did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration.1 In an interim analysis of the observational ELEANOR study (NCT04388384; N=187; 2020–ongoing), approx. 41%, 33%, and 19% of neratinib-treated pts received prior adjuvant trastuzumab (as their only anti-HER2 treatment), pertuzumab + trastuzumab, or T-DM1, respectively; corresponding rates of grade ≥3 diarrhea were 19%, 25%, and 14%, respectively, with no new safety signals reported.2 In a chart review from the US Oncology Network (N=166; 2017–2020), approx. 99%, 43%, and 2% of neratinib-treated pts received prior adjuvant trastuzumab (56% as their sole anti-HER2 treatment), pertuzumab, or T-DM1, respectively.3 Diarrhea was mainly moderate (29%; n=43/150) or mild (22%; n=33/150), with few severe cases (1%; n=2/150).3 In a retrospective analysis employing the IQVIA claims database (N=385; 2017–2021), prior use of recently approved adjuvant agents increased over time, with rates of prior pertuzumab + trastuzumab or prior T-DM1 as high as 52% and 14%, respectively, in 2020.4 In the Neat-HER virtual registry (N=46; 2018–2021), approx. 41% and 11% of neratinib-treated pts received prior adjuvant pertuzumab or T-DM1, respectively.5 Conclusions: Recent studies have observed neratinib use in clinical practice following adjuvant trastuzumab-based therapy including pertuzumab + trastuzumab or T-DM1. Preliminary data suggest a similar safety profile for pts with/without prior pertuzumab. These datasets are limited by the fact that: (1) some pts were enrolled in the CONTROL trial prior to launch of adjuvant T-DM1 and pertuzumab; (2) the interval between T-DM1 launch in Europe and start of the ELEANOR study was relatively short; and (3) not all toxicity measures were formally graded. A summary of available safety and effectiveness results is forthcoming. Additional interventional and non-interventional studies will continue to evaluate the safety and effectiveness of neratinib following current SOC adjuvant therapy in HER2+ EBC. Table 1. Treatment patterns of HER2-targeted adjuvant agents preceding neratinib use in HER2+ EBC ITT, intent-to-treat; T-DM1, ado-trastuzumab emtansine. aTherapies were recorded as used for adjuvant therapy in CONTROL, ELEANOR, US Oncology, and Neat-HER. CONTROL includes unpublished data. In the IQVIA claims analysis, HER2-targeted agent(s) used within 12 months prior to neratinib initiation were assumed to be adjuvant therapies. Pertuzumab use was generally taken in combination with trastuzumab as dual HER2 blockade and some pts received more than one anti-HER2 adjuvant treatment, for example T-DM1 in addition to pertuzumab plus trastuzumab. bAdjuvant trastuzumab monotherapy or in combination with chemotherapy unless noted otherwise. cThe proportion of patients who took at least one tablet of neratinib for ≥75% of the prescribed treatment days and did not take neratinib on days when neratinib was not prescribed. dData forthcoming. eIncludes prior trastuzumab monotherapy and trastuzumab used in combination with pertuzumab; 93/166 pts (56%) received trastuzumab as their only anti-HER2 agent (monotherapy or in combination with chemotherapy; unpublished data). fIncludes prior trastuzumab monotherapy as well as trastuzumab used in combination with pertuzumab. References Citation Format: Kelly McCann, Nadia Harbeck, Debu Tripathy, Arlene Chan, Jay Andersen, Joyce O'Shaughnessy, Gregory Vidal. Post-approval treatment patterns and tolerability of neratinib in HER2+ early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-08.

Abstract Db1-01: Anthracyclines …to give or not to give? “For” argument

Abstract Anthracyclines have been one of the mainstays of early breast cancer treatment for decades. In a recent patient-level meta-analysis including data from over 18,000 patients, anthracycline-containing regimens were associated with improvements in disease-free survival and overall survival, regardless of estrogen receptor or nodal status. Importantly, trials specifically designed and powered to assess the safety of anthracyclines omission failed to demonstrate the non-inferiority of taxane-based anthracycline-free regimens and confirmed the benefit of these agents, particularly in patients with node-positive and hormone receptor-negative breast cancer. Several therapies incorporated into the management of early breast cancer were studied in populations largely treated with anthracycline-based chemotherapy backbones in both HER2-negative (i.e., perioperative pembrolizumab, post neoadjuvant olaparib and capecitabine) and HER2-positive disease (i.e., dual HER2 blockade, adjuvant T-DM1). It is uncertain whether the benefits demonstrated by these strategies would be maintained if anthracyclines were omitted. While anthracyclines are associated with some long-term toxicities, particularly with an increased risk of lymphoproliferative malignancies and dose-dependent cardiotoxicity, these adverse events are not associated with an increased risk of death (including deaths from cardiovascular causes) when compared to anthracycline-free regimens. The identification of risk factors for cardiotoxicity, combined with improvements in monitoring strategies, allows improvements in patient selection, early detection of myocardial damage and, possibly, implementation of cardioprotective interventions, leading to improved cardiovascular outcomes. Until high-quality evidence demonstrates the safety of omitting anthracyclines in high-risk populations, these agents should continue to be used in carefully selected patients after individual risk versus benefit assessment to be shared with the patient. Citation Format: Martine Piccart, Guilherme Nader-Marta. Anthracyclines …to give or not to give? “For” argument [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Db1-01.

Abstract CT239: IMpower010: Updated overall survival and safety results from Asian patients in a Phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA NSCLC

Abstract Background The Phase III IMpower010 study (NCT02486718) met its primary endpoint at the disease-free survival (DFS) interim analysis (IA; clinical cutoff: Jan 21, 2021), demonstrating significant DFS improvement with atezolizumab (atezo) vs best supportive care (BSC) after adjuvant chemotherapy (chemo) in patients with resected stage II-IIIA NSCLC, including those with PD-L1 TC ≥1%. Based on these findings, atezo was approved as adjuvant therapy after platinum-based chemo in patients with completely resected PD-L1 TC ≥1% stage II-IIIA NSCLC in the US, China and other countries, and in patients with completely resected PD-L1 TC ≥50% stage II-IIIA NSCLC in the EU and other countries. In a previous exploratory analysis at the time of the DFS IA, the IMpower010 Asian subpopulation showed efficacy and safety outcomes that were consistent with those of the global population (Kenmotsu et al. JSMO 2021). Here we report updated data from the IMpower010 Asian subpopulation at the first overall survival (OS) IA. Methods The IMpower010 study design and DFS IA have been previously reported (Felip et al. Lancet 2021). Eligible patients with completely resected stage IB (≥4 cm)-IIIA NSCLC (AJCC/UICC v7) received one to four 21-day cycles of cisplatin-based doublet chemo and were subsequently randomized 1:1 to receive atezo 1200 mg q3w (16 cycles) or BSC. The first pre-specified OS IA was conducted at the clinical cutoff date of Apr 18, 2022. OS in the intention-to-treat (ITT) population will be formally tested if DFS in the ITT population reaches statistical significance at the final DFS analysis. Exploratory OS and updated safety outcomes were evaluated in the Asian subpopulation. Results The Asian ITT population included 233 patients recruited from Japan, mainland China, Taiwan, Korea and Hong Kong. At data cutoff (Apr 18, 2022), the unstratified OS HR was 0.73 (95% CI: 0.28, 1.88) in favor of atezo in the PD-L1 TC ≥1% (SP263) stage II-IIIA population (n=129). The Asian safety-evaluable population included 229 patients (atezo, n=122; BSC, n=107). Any-grade adverse events (AEs) were reported in 95.1% (atezo) and 72.0% (BSC) of safety-evaluable patients; events were Grade 3/4 in 24.6% and 13.1%, respectively. Grade 5 treatment-related AEs occurred in 1 patient in the atezo arm. AEs leading to atezo discontinuation occurred in 21.3% of patients treated with atezo. Conclusions The IMpower010 Asian subpopulation showed an OS trend favoring atezo vs BSC in the PD-L1 TC ≥1% stage II-IIIA population, as was observed in the global population, although OS data were not formally tested in either population at the first OS IA. With longer follow-up, the safety findings for atezo in the IMpower010 Asian subpopulation remained broadly unchanged, were consistent with those of the global IMpower010 population and were in line with the known safety profile of atezo. Medical writing support for this abstract was provided by Kia C. E. Walcott, PhD, of Nucleus Global, an Inizio Company, and funded by F. Hoffmann-La Roche, Ltd. Citation Format: Jie Wang, Yun Fan, Jian Fang, Jianxing He, Yunpeng Liu, Min Tao, Nasser Altorki, Enriqueta Felip, Heather Wakelee, Eric Vallieres, Rossella Belleli, Virginia McNally, Elizabeth Bennett, Barbara J. Gitlitz, Caicun Zhou. IMpower010: Updated overall survival and safety results from Asian patients in a Phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT239.

Neoadjuvant Chemotherapy in Patients with HER2-Negative Breast Cancer: A Report from Clinical Breast Cancer Registry of Iran.

Neoadjuvant chemotherapy (NCT) has become an increasingly popular approach in management of breast cancer (BC). This study was conducted to evaluate the pathologic response and 36-month recurrence and survival rates of patients with human epidermal growth factor receptor 2 (HER2)-negative BC treated with different NCT regimens. A total of 163 female patients with HER2-negative BC who received NCT during 2017-2020 were identified from the Clinical Breast Cancer Registry of Iran and entered the study. The prescribed NCT regimens included 4 cycles of doxorubicin plus cyclophosphamide, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of paclitaxel, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of docetaxel or 6 cycles of doxorubicin plus cyclophosphamide plus docetaxel (TAC). Thirty-two patients (19.6%) experienced pathologic complete response (pCR). TAC regimen, triple negative-BC and ki67>10% were significantly associated with increased pCR. The recurrence, overall survival (OS) and disease-free survival (DFS) rate at 36 months for all patients were 16.6%, 84.7% and 79.8%, respectively. Type of neoadjuvant regimen as well as age, hormone receptor status, Ki67, grade, clinical stage, type of surgery and pathologic response to chemotherapy did not significantly influence the survival and recurrence; however, TAC results in improved recurrence, OS and DFS rates. This study provides further evidence that NCT is a viable treatment option for patients with HER2-negative BC. The TAC regimen resulted in a significantly higher pCR rate compared to other regimens, but did not result in a significant improvement in recurrence, OS and DFS and rates.

Randomized, Double-Blind Phase III Study of Pazopanib Versus Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease After Metastasectomy: ECOG-ACRIN E2810.

Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy. Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate. From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; Pone-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo (Ptwo-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period. Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.

AMBASSADOR Alliance A031501: Phase III randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (MIUC) vs observation.

LBA531 Background: Muscle-invasive urothelial carcinoma (MIUC) is an aggressive disease with high relapse rates. Neoadjuvant platinum-based chemotherapy (NAC) is the standard of care in patients (pts) who are cisplatin (Cis)-eligible. However, many pts are Cis-ineligible or have persistent muscle-invasive disease after NAC and surgery. We evaluated pembrolizumab (Pembro) as adjuvant therapy in pts with high-risk MIUC following surgical resection. Methods: The AMBASSADOR study is an open-label, randomized, phase III trial that enrolled pts with histologically confirmed MIUC of the bladder, upper tract, or urethra who (1) had ≥ pT2 and/or pN+ or margins+ at surgery (radical cystectomy, nephrectomy, nephroureterectomy, or ureterectomy) following NAC or (2) ≥ pT3 and/or pN+ or margins+ at surgery without NAC and were either Cis-ineligible or declined adjuvant Cis-based therapy. Pts were registered ≥4 to 16 weeks after surgery and randomized 1:1 to receive Pembro 200 mg every 3 weeks for 1 year or observation (Obs). Randomization was stratified by pathologic stage, centrally tested PD-L1 status, and prior NAC. The dual primary endpoints were disease-free survival (DFS) and overall survival (OS) with a target sample size of 739 pts and required 387 DFS and 320 OS events for final analysis. Secondary objectives included evaluation of DFS and OS in PD-L1-positive and -negative pts and assessing safety. Here we present the interim DFS and OS results. Results: Between 09/2017 and 08/2021 a total of 702 pts were randomized prior to early closure due to US FDA approval of nivolumab for MIUC pts: 354 pts to Pembro and 348 pts to Obs; 13.0% vs 21.6% withdrew from study without event in the Pembro vs Obs arms, respectively. 74 pts (21%) in the Obs arm received an immune checkpoint inhibitor. Median follow-up was 22.3 months (mos) for DFS and 36.9 mos for OS. The DFS endpoint (based on 319 events needed for interim analysis) crossed the efficacy boundary. Median DFS was 29.0 months (95% confidence interval (CI) 21.8‒not evaluable (NE)) with Pembro and 14.0 months (95% CI 9.7‒20.20) with Obs (hazard ratio (HR) 0.69 [95% CI 0.55–0.87]; p=0.0013). At the interim analysis (n = 257 events), median OS was 50.9 months (95% CI 43.9‒NE) with Pembro and 55.8 months (95% CI 53.3‒NE) with Obs (HR 0.98 [95% CI 0.76–1.26]; p=0.88). Grade 3+ adverse events occurred in 48.4% and 31.8% of pts in the Pembro and Obs arms, respectively. Conclusions: Adjuvant Pembro demonstrated a statistically significant and clinically meaningful improvement in DFS vs Obs for high-risk MIUC pts after radical surgery. The OS endpoint may have been impacted by pts on the Obs arm receiving a checkpoint inhibitor. Pembro was tolerable with no new safety signals. These results support adjuvant Pembro as a new therapeutic option for pts with MIUC with high risk for recurrence. Additional follow-up is ongoing for the final DFS/OS, PD-L1 subgroups, and ctDNA analyses. Clinical trial information: NCT03244384 .

Prognostic factors in surgically treated tongue squamous cell carcinoma in stage T1-2N0-1M0: A retrospective analysis.

The study aimed to retrospectively identify the prognostic factors of surgically treated primary tongue squamous cell carcinoma (TSCC) cases and assess the benefits of surgical neck lymph node dissection (LND) in early-stage cancer. Patients with primary TSCC with pT1-2N0-1M0 stage without distant metastasis who were treated with surgery during 2014-2016 at Xiangya Hospital, Central South University were included. Univariate and multivariate Cox models were constructed to explore prognostic factors of overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS). Sub-group analysis was used to assess the effect of adjuvant therapy and the prognostic value of LND for the early-stage patients. In total, 440 patients met the inclusion criteria. During the follow-up period, the 5-year OS, DFS, were 84.4% and 70.0%, respectively. Univariate analysis showed that TNM stage, lymphovascular invasion (LVI), and/or perineural invasion (PNI), pathological differentiation, etc. were significant predictors of OS and DFS. Multivariate analysis showed that TNM stage and the degree of pathological differentiation were independent prognostic factors for all outcomes. Besides, the number of cervical LND could independently predict both DFS and LRFS while LVI/PNI were associated with DFS. And high-quality neck LND (≥30) significantly improved DFS and LRFS for patients of pT1cN0M0 or stage I as compared to those without LND. TNM stage and pathological differentiation were crucial prognostic factors for postoperative patients with TSCC. Notably, high-quality cervical LND was beneficial for the improvement of DFS and LRFS for patients of pT1cN0M0 or stage I.

Effect of adjuvant chemotherapy on the oncological outcome of rectal cancer patients with pathological complete response

BackgroundLocally advanced rectal cancer is typically treated using a combination of neoadjuvant chemoradiotherapy and total mesorectal resection. While achieving pathological complete response following neoadjuvant chemoradiotherapy has been recognized as a positive prognostic factor in oncology, the necessity of adjuvant chemotherapy for locally advanced rectal cancer patients with pathological complete response after surgery remains uncertain. The objective of this meta-analysis was to examine the impact of adjuvant chemotherapy on the oncological outcomes of rectal cancer patients who attain pathological complete response after neoadjuvant chemoradiotherapy.MethodsThis meta-analysis followed the guidelines outlined in the preferred reporting items for systematic review and meta-analysis (PRISMA). The Web of Science, PubMed, and Cochrane Library databases were systematically searched to identify relevant literature.ResultsA total of 34 retrospective studies, including 9 studies from the NCBD database, involving 31,558 patients with pathological complete response rectal cancer, were included in the meta-analysis. The included studies were published between 2008 and 2023. The pooled analysis demonstrated that adjuvant chemotherapy significantly improved overall survival (HR = 0.803, 95% CI 0.678–0.952, P = 0.011), and no heterogeneity was observed (I2 = 0%). Locally advanced rectal cancer patients with pathological complete response who underwent adjuvant chemotherapy exhibited a higher 5-year overall survival rate compared to those who did not receive adjuvant chemotherapy (OR = 1.605, 95% CI 1.183–2.177, P = 0.002). However, the analysis also revealed that postoperative ACT did not lead to improvements in disease-free survival and recurrence-free survival within the same patient population. Subgroup analysis indicated that pathological complete response patients with clinical stage T3/T4, lymph node positivity, and younger than 70 years of age may benefit from adjuvant chemotherapy in terms of overall survival.ConclusionsThe findings of this meta-analysis suggest that adjuvant chemotherapy has a beneficial effect on improving overall survival among rectal cancer patients with pathological complete response. However, no such association was observed in terms of disease-free survival and recurrence-free survival.

Treatment decision for recurrences in non-small cell lung cancer during or after adjuvant osimertinib: an international Delphi consensus report.

Osimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence. To reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy. Panellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made. This study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment.

(Neo)adjuvant approaches in lung cancer—paving the road to a cure

SummaryImmune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of metastatic non-small-cell lung cancer (NSCLC). During the past few years the focus of research has shifted toward examining these therapies in patients with early-stage NSCLC to improve long-term overall survival and cure rates. As recurrence rates are high and the relapse pattern in patients with completely resected early-stage NSCLC is predominantly systemic, high expectations rest on the integration of ICI therapy in their treatment approach. A large number of studies with adjuvant or neo-adjuvant ICI are ongoing. The first data from phase III studies have demonstrated improvements in disease-free survival and pathologic remissions, but overall survival data are mostly immature. Additionally, targeted therapies have also been explored in early-stage NSCLC. The first very promising results are available from EGFR-mutant and ALK-translocated NSCLC and have already changed our clinical practice for some patient subgroups. This review discusses the most recent results of phase III trials in the neoadjuvant, perioperative, and adjuvant setting for ICI and targeted therapies in early-stage resectable NSCLC.

Adjuvant Osimertinib in Patients With Stage IB to IIIA EGFR Mutation-Positive NSCLC After Complete Tumor Resection: ADAURA China Subgroup Analysis

IntroductionIn Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People’s Republic of China from ADAURA. MethodsIn ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. ResultsOf 682 patients enrolled globally, 159 patients in the People’s Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13–0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17–0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21–1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. ConclusionsIn this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

Gene expression alterations predict the pathological complete response in triple-negative breast cancer exploratory analysis of the NACATRINE trial

This exploratory analysis of the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE) study aimed to identify the biomarkers of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC) within the context of a clinical trial. The NACATRINE trial is a phase II, single-center, randomized, open-label clinical trial that investigated the addition of carboplatin to sequential anthracycline- and taxane-based NAC for TNBC. We evaluated the gene expression in untreated samples to investigate its association with pCR, overall survival (OS), and disease-free survival (DFS). RNA was extracted from the tissue biopsy, and the nCounter Breast Cancer panel was used to analyze gene expression. Of the 66 patients included in the gene expression profiling analysis, 24 (36.4%) achieved pCR and 42 (63.6%) had residual disease. In unsupervised hierarchical clustering analyses, differentially expressed genes between patients with and without pCR were identified irrespective of the treatment (24 genes), carboplatin (37 genes), and non-carboplatin (27 genes) arms. In receiver operating characteristic (ROC) curve analysis, 10 genes in the carboplatin arm (area under the ROC curve [AUC], 0.936) and three genes in the non-carboplatin arm (AUC, 0.939) were considered to be potential pCR-associated biomarkers. We identified genes that were associated with improvements in OS and DFS in addition to being related to pCR. We successfully identified gene expression signatures associated with pCR in pretreatment samples of patients with TNBC treated with NAC. Further investigation of these biomarkers is warranted.

Reduced Intensity Condition of ATG Based Haploidentical Hematopoietic Stem Cell Transplantation in Elderly or Unfit Patients

Aims: Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of ATG based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in elderly or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG based haploidentical HSCT. Methods: We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30mg/m²/kg 6 days combined with busulfan 3.2mg/kg 2 days (Bu2) or 3 days (Bu3). Results: The median age of patients in the entire cohort was 60 (32 - 67) years with a median follow-up of 496 (83 - 2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8% - 85.1%) and 61.4% (95% CI, 48.8% - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8 % (95% CI, 4.8% - 19.6%) and 9.7 % (95% CI, 0.0% - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9% - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5% - 33.7%) and 11.6% (95% CI, 2.2% - 21.9 %) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5%-85.3%) in Bu2 and 85.5%（95% CI:73.0%-100%) in Bu3 group respectively(P=0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0%-74.8%) in Bu2 and 72.6% (95% CI:55.5%-95.5%) in Bu3 group respectively (P=0.045). The 2-year IR or 2-year NRM were not significantly different between Bu2 and Bu3 group(P&amp;gt;0.05). In multivariable analysis, RIC regimen of Bu3 had superior DFS and lower RI than Bu2 group respectively [HR 0.41, 95% CI 0.16-1.01; P=0.05; HR 0.33, 95% CI 0.11-0.99; P=0.047]. Conclusion: The RIC regime of ATG based haploidentical HSCT is a safe and effective treatment option for patients who are elderly or have poor functional status, making them unable to tolerate intensive chemotherapy. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in DFS, thus providing more favorable post-transplantation clinical outcomes.