Disease-free Survival Benefit Research Articles

A real-world retrospective study to assess efficacy and safety of alectinib as adjuvant therapy in IB-IIIB NSCLC patients harboring ALK rearrangement

BackgroundAlectinib has demonstrated promising disease-free survival (DFS) benefit for early-stage non-small cell lung cancer (NSCLC) patients with ALK rearrangement positive in phase 3 ALINA trial. However, real-world evidence for the efficacy and safety of alectinib in early-stage ALK-positive NSCLC is limited.Materials and methodsWe retrospectively reviewed 68 patients with stage IB-IIIB ALK-positive NSCLC who underwent complete pulmonary resections from April 2010 to July 2023 at a single institution. 38 (55.9%) enrolled patients had N2 lymph node metastasis, and 17 (24.9%) patients had multi-station N2 metastasis. Patients were stratified into two groups according to the adjuvant treatment regimen, with 19 patients in the alectinib group and 49 patients in the chemotherapy group. There were no significant differences in clinicopathological characteristics between the two groups. After curative resection surgery, patients in alectinib group received oral alectinib at a dose of 600 mg twice daily and patients in chemotherapy group received platinum-based doublet chemotherapy regimen every 3 weeks for 4 cycles. The primary endpoint was 3-year DFS. The Kaplan-Meier method was used to estimate DFS and overall survival (OS). Safety analyses were conducted by comparing the incidence of adverse events between the two groups.ResultsAt the last follow-up date (January 22th, 2024), A total of 1 (5.3%) and 28 (57.1%) DFS events were observed in alectinib group and chemotherapy group respectively. The 3-year DFS showed significant improvement in the alectinib group compared with chemotherapy group (91.7% vs 60.7%, P=0.051). In the IIIAN2 subgroup, the 3-year DFS rate in the alectinib group reached a satisfactory 87.5%. In both groups, the majority of AEs were graded as level 1 or 2, No grade 3-4 AEs were observed in alectinib group.ConclusionAlectinib, as adjuvant therapy, demonstrated favorable efficacy and manageable safety in patients with completely resected ALK-positive stage I B-IIIB non-small cell lung cancer. A limitation of this study is the small sample size, and a larger-scale real-world sample study is needed to further evaluate the efficacy and safety of alectinib as adjuvant therapy.

Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.CheckMate 274 is a phase III, randomized, double-blind trial of adjuvant nivolumab versus placebo for muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence after radical resection. The primary end points of disease-free survival (DFS) in intent-to-treat (ITT) and tumor PD-L1 expression ≥1% populations were met. We report results at an extended median follow-up of 36.1 months in the ITT population. In addition, we report interim overall survival (OS) data for the first time and an exploratory analysis among patients with bladder primary tumors (muscle-invasive bladder cancer [MIBC]). Consistent DFS benefit with nivolumab versus placebo was observed in both the ITT (hazard ratio [HR], 0.71 [95% CI, 0.58 to 0.86]) and PD-L1 ≥1% (HR, 0.52 [95% CI, 0.37 to 0.72]) patients. The HR for OS with nivolumab versus placebo was 0.76 (95% CI, 0.61 to 0.96) in the ITT population and 0.56 (95% CI, 0.36 to 0.86) in the PD-L1 ≥1 population. Continuous benefit in nonurothelial tract recurrence-free survival and distant metastasis-free survival was also observed in both patient populations. The exploratory analysis of patients with MIBC also showed continued efficacy benefits, irrespective of PD-L1 status. No new safety signals were reported. Overall, these results further support adjuvant nivolumab as a standard of care for high-risk MIUC after radical resection.

Retrospective analysis of multiparametric MRI in predicting complete pathologic response of neo-adjuvant chemotherapy in bladder cancer

BackgroundMuscle invasive bladder cancer (MIBC) treatment combines systemic therapy and radical cystectomy (RC) or local (chemo-)radiotherapy. Response to systemic therapy is an important outcome predictor but is difficult to assess pre-operatively.MethodsWe analyzed multiparametric MRI (mpMRI) in consecutive MIBC patients receiving cisplatin-based neo-adjuvant chemotherapy at our institution. Two readers, blinded for pathological outcome, independently scored mpMRI before and after 2 and 4 cycles using both a qualitative 3-step method and nacVI-RADS. We analyzed accuracy of mpMRI scores to predict pathologic complete response (pCR) and inter-observer agreement.ResultsWe analyzed 46 patients receiving NAC, 6 patients did not undergo RC after NAC and were excluded. Eleven out of 40 (28%) patients showed a pCR. mpMRI could be assessed in over 90% of patients. Radiologic complete response (rCR) using both methods was significantly associated with pCR, with an overall specificity of 96% and sensitivity of 36% and a high inter-observer agreement. rCR as assessed by the 3-step score was significantly associated with disease free survival (DFS) benefit.ConclusionThe use of nacVI-RADS can predict pCR after NAC with high specificity but low sensitivity and a high inter-observer agreement. A 3-step score adds value in determining local residual disease, rCR assessed by this method could correlate with DFS benefit. mpMRI scores should be prospectively assessed in future trials of multimodal management of MIBC and can be a predictive asset in routine clinical management.

Stratifying the Risk of Disease Progression among Surgically Treated Muscle-Invasive Bladder Cancer Eligible for Adjuvant Nivolumab.

Background: Check-Mate 274 has demonstrated the disease-free survival (DFS) benefit of adjuvant nivolumab in surgically treated muscle-invasive bladder cancer (MIBC). Since immunotherapy represents an expensive treatment with potential side effects, a better understanding of patient-specific risks of disease progression might be useful for clinicians when weighing the indication for adjuvant nivolumab. Objective: To identify the criteria for risk stratification of disease progression among MIBC patients eligible for adjuvant nivolumab. Materials and methods: A single-institution, prospectively maintained database was queried to identify patients eligible for adjuvant nivolumab according to Check-Mate 274 criteria. To account for immortal bias, patients who died or were lost to follow-up within 3 months of undergoing a radical cystectomy (RC) were excluded. Kaplan-Meier and Cox regression analyses addressed DFS, defined as the time frame from diagnosis to the first documented recurrence or death from any cause, whichever occurred first. Regression tree analysis was implemented to identify criteria for risk stratification. Results: Between 2011 and 2022, 304 patients were identified, with a median follow-up of 50 (IQR 24-72) months. After multivariable adjustment, including NAC as a potential confounder, higher CCI (HR 1.56, 95%CI 1.10-2.21, p = 0.013), T stage (HR 2.06, 95%CI 1.01-4.17, p = 0.046), N stage (HR 1.73, 95%CI 1.26-2.38, p = 0.001) and presence of LVI (HR 1.52, 95%CI 1.07-2.15, p = 0.019) increased the risk of disease recurrence or death. Finally, a two-tier classification was developed. Here, five-year DFS rates were 56.1% vs. 18.1 for low vs. high risk (HR: 2.54, 95%CI 1.79-3.62, p < 0.001). Conclusions: The current risk classification, if externally validated on larger samples, may be useful when weighing the risk and benefit of adjuvant nivolumab treatment and making patients more aware about their disease and about the need for additional treatment after RC.

Neoadjuvant chemoradiotherapy for T3N0M0 esophageal squamous cell carcinoma

The optimal treatment for patients with pretreatment T3N0M0 (pre-T3N0M0) esophageal squamous cell carcinoma (ESCC) remains controversial. This study evaluated the impact of neoadjuvant chemoradiotherapy (NCRT) on the survival outcomes of individuals diagnosed with pre-T3N0M0 ESCC. A total of 443 patients with pre-T3N0M0 ESCC who underwent either NCRT plus surgery (NCRT + S) or surgery alone were included in the study. In the surgery group, patients with post-operative staging of pathological T3N0M0 (pT3N0M0) were classified as pre-T3N0M0. In the NCRT + S group, due to tumor downstaging after NCRT, patients with pre-treatment clinical T3 and post-operative pathology indicating lymph nodes without evidence of tumor involvement or regression were considered to have pre-T3N0M0. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors influencing overall survival (OS) in pre-T3N0M0 patients. Kaplan&amp;ndash;Meier curves were employed to assess disparities in OS and disease-free survival (DFS) between the two groups. Compared to surgery alone, NCRT + S significantly enhanced the OS (Hazard ratio [HR] = 0.572, 95% Confidence interval [CI] = 0.407 &amp;ndash; 0.804; P = 0.0059); however, it did not show a significant benefit in DFS (HR = 0.784, 95% CI = 0.564 &amp;ndash; 1.09; P = 0.17). Compared with the surgery group, patients who achieved a pathologically complete response (pCR) after NCRT showed significantly improved OS (HR = 0.522, 95% CI = 0.339 &amp;ndash; 0.804; P = 0.019). The overall and locoregional recurrence rates were significantly lower in the NCRT + S group than in the surgery group. Compared with surgery alone, NCRT + S significantly improved OS in patients with pre-T3N0M0 stage disease, especially in those who achieved pCR after NCRT.

Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: subgroup analysis from CIRCULATE-Japan GALAXY

The prognostic role of circulating-tumor DNA (ctDNA)-based molecular residual disease (MRD) detection and its utility for postsurgical risk-stratification has been reported in colorectal cancer. In this study, we explored the use of ctDNA-based MRD detection in patients with colorectal liver metastases (CLM), for whom the survival benefit of adjuvant chemotherapy (ACT) after surgical resection remains unclear. Patients with CLM without extrahepatic disease from GALAXY study (UMIN000039205) were included. The disease-free survival (DFS) benefit of ACT was evaluated in MRD-positive and -negative groups after adjusting for age, gender, number and size of liver metastases, RAS status, and previous history of oxaliplatin for primary cancer. ctDNA was detected using a personalized, tumor-informed 16-plex mPCR-NGS assay. ctDNA-based MRD status was evaluated 2 to 10 weeks after curative surgery, before the start of ACT. Among 6,061 patients registered in GALAXY, 190 surgically resected CLM patients without any preoperative chemotherapy were included with a median follow-up of 24 (1-48) months. ctDNA positivity in the MRD window was 32.1% (61/190). ACT was administered to 25.1% (48/190) of patients. In the MRD-positive group, 24-month DFS was higher for patients treated with ACT (33.3% vs. not reached, adjusted HR: 0.07, P <0.0001); whereas no benefit of ACT was seen in the MRD-negative group (24-month DFS: 72.3% vs. 62.2%, adjusted HR: 0.68, P =0.371). Multivariate analysis showed that the size of liver metastases (HR: 3.94, P =0.031) was prognostic of DFS in the MRD-positive group. However, in the MRD-negative group, none of the clinicopathological factors were prognostic of DFS. Our data suggest that ACT may offer notable clinical benefits in MRD-positive patients with CLM. MRD status-based risk-stratification could be potentially incorporated in future clinical trials for CLM.

Total Body Irradiation and Fludarabine with Post-Transplantation Cyclophosphamide for Mismatched Related or Unrelated Donor Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (HCT) remains the sole curative treatment for most patients with hematologic malignancies. A well-matched donor (related or unrelated) remains the preferred donor for patients undergoing allogeneic HCT; however, a large number of patients rely on alternative donor choices of mismatched related (haploidentical) or unrelated donors to access HCT. In this retrospective study, we investigated outcomes of patients who underwent mismatched donor (related or unrelated) HCT with a radiation-based myeloablative conditioning MAC regimen in combination with fludarabine, and post-transplantation cyclophosphamide (PTCy) as higher-intensity graft-versus-host disease (GVHD) prophylaxis. We retrospectively assessed HCT outcomes in 155 patients who underwent mismatched donor HCT (related/haploidentical versus unrelated [MMUD]) with fractionated-total body irradiation (fTBI) plus fludarabine and PTCy as GVHD prophylaxis at City of Hope from 2015 to 2021. Diagnoses included acute lymphoblastic leukemia (46.5%), acute myelogenous leukemia (36.1%), and myelodysplastic syndrome (6.5%). The median age at HCT was 38 years, and 126 patients (81.3%) were an ethnic minority. The Hematopoietic Stem Cell Transplantation Comorbidity Index was ≥3 in 36.1% of the patients, and 29% had a Disease Risk Index (DRI) of high/very high. The donor type was haploidentical in 67.1% of cases and MMUD in 32.9%. At 2 years post-HCT, disease-free survival (DFS) was 75.4% and overall survival (OS) was 80.6% for all subjects. Donor type did not impact OS (hazard ratio [HR], .72; 95% confidence interval [CI], .35 to 1.49; P = .37) and DFS (HR, .78; 95% CI, .41 to 1.48; P = .44), but younger donors was associated with less grade III-IV acute GVHD (HR, 6.60; 95% CI, 1.80 to 24.19; P = .004) and less moderate or severe chronic GVHD (HR, 3.53; 95% CI, 1.70 to 7.34; P < .001), with a trend toward better survival (P = .099). The use of an MMUD was associated with significantly faster neutrophil recovery (median, 15 days versus 16 days; P = .014) and platelet recovery (median, 18 days versus 24 days; P = .029); however, there was no difference in GVHD outcomes between the haploidentical donor and MMUD groups. Nonrelapse mortality (HR, .86; 95% CI, .34 to 2.20; P = .76) and relapse risk (HR, .78; 95% CI, .33 to 1.85; P = .57) were comparable in the 2 groups. Patient age <40 years and low-intermediate DRI showed a DFS benefit (P = .004 and .029, respectively). High or very high DRI was the only predictor of increased relapse (HR, 2.89; 95% CI, 1.32 to 6.34; P = .008). In conclusion, fludarabine/fTBI with PTCy was well-tolerated in mismatched donor HCT, regardless of donor relationship to the patient, provided promising results, and increased access to HCT for patients without a matched donor, especially patients from ethnic minorities and patients of mixed race.

Preoperative imaging of colorectal liver metastases: what the radiologist and the multidisciplinary team need to know.

The management of patients with colorectal liver metastases (CRLM) has transformed over the past 2 decades. Advances in surgical techniques, systemic therapies, and local treatments have resulted in a paradigm shift. Disease that would once have been considered terminal is now frequently treated aggressively with both a disease-free and overall survival benefit. In line with the expanding range of treatment options, there has been an increase in the volume and complexity of imaging required in the management of these patients to ensure optimal patient selection and outcome. The radiologist plays a pivotal role in interpreting these studies, conveying the relevant information and informing the discussion at multidisciplinary team meetings. The purpose of this review is to provide an update for radiologists on the current surgical management of patients with CRLM highlighting specific imaging information that is required by the multidisciplinary team when assessing resectability and/or the need for additional liver-directed therapies.

Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial

The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P= 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P= 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P= 0.033). The safety profile remained unchanged since the previous analysis. Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients.

Approaches to Treating High Risk and Advanced Renal Cell Carcinoma (RCC): Key Trial Data That Impacts Treatment Decisions in the Clinic.

The treatment paradigm for high risk localized and advanced kidney cancer has been characterized by ongoing changes, with the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and later with immune checkpoint blockade. In this article, we review how current evidence informs our decision-making on post-checkpoint inhibitor systemic therapies, the role of adjuvant and/or neoadjuvant therapies, and the role of cytoreductive nephrectomy in the evolving systemic therapy landscape. While some studies support a post-checkpoint inhibitor benefit from the VEGFR TKIs cabozantinib or axitinib, the benefit of doublet therapies including a VEGF receptor inhibitor and a checkpoint inhibitor remains an area of active investigation, with the combination of lenvatinib plus pembrolizumab showing promise but with a Phase III trial of the combination of atezolizumab plus cabozantinib showing no benefit over cabozantinib alone. The role of adjuvant therapy in patients with high-risk disease who have undergone cytoreductive nephrectomy and potentially metastasectomy is also an area of continuing interest. While the S-TRAC study demonstrated a disease-free survival benefit for adjuvant sunitinib, no overall survival benefit was shown, and multiple other studies of adjuvant VEGFR TKI therapy have been negative. Subsequently, adjuvant pembrolizumab has shown a benefit in overall survival, whereas trials of neoadjuvant and adjuvant nivolumab, adjuvant atezolizumab, and adjuvant ipilimumab plus nivolumab have all been negative. Finally, the role for cytoreductive nephrectomy continues to be an area of active debate. The CARMENA study raised important questions about the role of cytoreductive nephrectomy given the advances in VEGFR TKI therapy but was characterized by accrual difficulties and a significant number of patients not receiving treatment according to the study protocol. Two ongoing studies (NORDIC-SUN and PROBE) seek to further address the role of cytoreductive nephrectomy in the doublet therapy era.

Adjuvant Treatment of Stage I-II Serous Endometrial Cancer: A Single Institution 20-Year Experience.

Background: Serous endometrial carcinoma (SEC) is a high-risk subtype of endometrial cancer. The effectiveness of multiple adjuvant therapies, namely chemotherapy (CT), radiotherapy (RT), and sequential/concurrent chemotherapy with radiotherapy (CRT), have previously been investigated. However, optimal management of early-stage SEC remains unclarified. Methods: All cases of early-stage SEC (FIGO 2009 stages I-II) treated in our institution from 2002 to 2019 were identified. Patient data were documented until September 2023. Overall survival (OS) and disease-free survival (DFS) were computed using Kaplan-Meier estimates and Cox's proportional hazard model; descriptive statistical analysis was performed. Results: A total of 50 patients underwent total hysterectomy-bilateral salpingo-oophorectomy and omentectomy, displaying stage IA (60%), IB (24%), and II (16%) disease. The median follow-up was 90.9 months. Patients underwent adjuvant CRT (n = 36, 72%), CT (n = 6, 12%), or RT (n = 6, 12%). Two patients were observed and excluded from analyses. The 42 patients who received radiotherapy had pelvic external beam radiotherapy (n = 10), vaginal brachytherapy (n = 21), or both (n = 11). CRT had better OS (HR 0.14, 95%CI 0.04-0.52, p < 0.005) and DFS (HR 0.25, 95%CI 0.07-0.97, p = 0.05) than CT alone. RT displayed no OS or DFS benefits compared to CT/CRT. Recurrences were mostly distant. Acute and late G3-4 toxicities were primarily hematologic. Conclusions: Our data underline the challenge of treating SEC. CRT appears to be superior to CT alone but not to RT. Most recurrences were distant, highlighting the need for optimized systemic treatment options.

IMpower010: Final disease-free survival (DFS) and second overall survival (OS) interim results after ≥5 years of follow up of a phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA non-small cell lung cancer (NSCLC).

LBA8035 Background: IMpower010 (NCT02486718) met its primary endpoint of significant DFS improvement with atezo vs BSC after adj chemotherapy in resected NSCLC in the PD-L1 TC ≥1% and all-randomized stage II-IIIA populations, leading to worldwide approval of adj atezo for PD-L1 TC ≥1% or PD-L1 TC ≥50% stage II-IIIA NSCLC. At OS IA1, a trend favoring atezo was seen in the PD-L1 TC ≥1% stage II-IIIA population. Here we report findings from the DFS FA and OS IA2. Methods: The IMpower010 study design has been previously described (Felip et al, Lancet 2021). The primary DFS and secondary OS endpoints were tested hierarchically: DFS in the PD-L1 TC ≥1% (SP263) stage II-IIIA, then in the all-randomized stage II-IIIA, and then in the intent-to-treat (ITT; stage IB-IIIA) populations, followed by OS in the ITT population. Secondary endpoints included 3- and 5-y DFS and DFS in the PD-L1 TC ≥50% (SP263) stage II-IIIA population. OS in the ITT population could only be formally tested if the significance boundary for DFS in that population was crossed. Results: At the DFS FA and OS IA2 (clinical cutoff date: Jan 26, 2024), with a minimum follow-up of 60 mo, DFS and OS for the PD-L1 TC ≥1% and TC ≥50% stage II-IIIA populations were consistent with previously observed benefit; the difference in median (m) DFS between arms in the PD-L1 TC ≥1% population was 31.2 mo (Table). In the ITT population, the significance boundary for DFS was not crossed and OS was similar between arms, although data were immature. The safety profile of atezo was consistent with prior analyses. Conclusions: These results provide the first cancer immunotherapy data with ≥5 y of follow-up from a Phase III study in resectable NSCLC. Although the statistical boundary for the ITT population was not crossed, DFS benefit with adj atezo continues to translate into a positive OS trend vs BSC in the PD-L1 TC ≥1% and TC ≥50% stage II-IIIA populations. These results further support the use of adj atezo in PD-L1–selected populations. Clinical trial information: NCT02486718 . [Table: see text]

Is there a correlation between estrogen receptor expression level and early breast cancer survival? A retrospective study.

e12574 Background: The optimal cut-off of estrogen receptor (ER) positivity is still debatable; however, adjuvant hormonal therapy is usually given if ER expression is ≥ 1%. The present study aims to assess the clinicopathological features and survival outcomes of patients with low compared to high ER expression levels. Methods: In this retrospective, we checked non-metastatic hormonal receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who presented to three hospitals in Egypt and Saudi Arabia between 2016 and 2019. Different clinicopathological factors and data on relapse were checked in patients’ medical records. These data were compared in patients with ER-Low (1–10%) vs. ER-High (&gt;10%) expression levels. Results: We included 419 patients who met the eligibility criteria for the study. Only 3.3% of patients had ER-Low. Compared to the ER-high group, the ER-low expression group was more likely to have grade 3 tumours (64.3% vs. 21.0%, p = &lt;0.0001) and PR-negative tumors (64.3% vs. 16.3%, p = &lt;0.0001). Furthermore, younger age (≤ 50 years) was more frequent in the ER-Low group compared to ER-High patients (71.4% vs. 42.5%, respectively, p = 0.032). Likewise, ER-high patients were more likely to have high ER-staining intensity (74.1% vs. 0.0%, p&lt;0.0001). Disease-free survival (DFS) was numerically improved in patients with ER-high, but without statistical significance. After adjustment of different clinicopathological prognostic factors, the DFS benefit in the ER-high group was more definite (hazard ratio (HR) = 3.59, 95%, confidence interval (CI) = 1.11–11.55, and p value = 0.032). Conclusions: A lower estrogen receptor expression level (varying from 1 to 10%) in hormone-positive early breast cancer patients is an uncommon pattern associated with more aggressive disease features at diagnosis. This group of patients had a lower DFS than those with a higher degree of estrogen receptor expression, although there was no statistically significant difference in OS.

Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small-cell lung cancer (ICTAN, GASTO1002): A randomized phase 3 trial.

8004 Background: The efficacy, safety and ideal treatment duration of adjuvant icotinib (first-generation EGFR tyrosine kinase inhibitor) for patients with completely resected EGFR-mutated non-small-cell lung cancer (NSCLC) after adjuvant chemotherapy were not known in 2014, when this study was initiated. This phase 3 trial investigated whether icotinib following adjuvant chemotherapy improves clinical outcomes compared with observation in stage II-IIIA NSCLC harboring EGFR mutation. Methods: This is a multicenter, randomized, open-label, phase 3 trial. From July 2014 to December 2021, patients with completely resected, EGFR-mutated, stage II-IIIA NSCLC after platinum-based adjuvant chemotherapy were enrolled. Patients were assigned in a 1:1:1 ratio to receive icotinib (125mg, three times daily) for 12 months, icotinib for 6 months or to observation. The primary endpoint was disease-free survival (DFS) in the intention-to-treat population. Results: This trial was terminated early due to slow accrual.A total of 251 patients were randomized, with 84 patients in the 12-month icotinib group, 84 patients in the 6-month icotinib group, and 83 patients in the observation group. Baseline characteristics were balanced between the groups. After a median follow-up of 61.4 months, 6 months of icotinib significantly improved DFS (HR: 0.41, 95% CI, 0.27-0.62; P = 0.000025) and overall survival (OS, HR: 0.56, 95% CI, 0.32-0.98; P = 0.041) compared with observation. Adjuvant icotinib of 12 months also significantly improved DFS (HR: 0.40, 95% CI, 0.27-0.61; P = 0.000014) and OS (HR: 0.55, 95% CI, 0.32-0.96; P = 0.035) compared with observation. Adjuvant icotinib of 12 months did not improve DFS (HR: 0.97; P = 0.89) and OS (HR: 1.00; P = 0.99) compared with 6 months of this drug. Median DFS was 61.8 months (95% CI, 43.3 to 80.3) for the 12-month icotinib group, 63.2 months (95% CI, 44.8 to 81.6) for the 6-month icotinib group compared with 23.7 months (95% CI, 16.5 to 30.9) for the observation group. The 5-year DFS and OS for the 12-month icotinib, 6-month icotinib and observation groups were 51.3%, 50.1% and 24.8%; and 74.5%, 74.0% and 65.1%; respectively. No differences in efficacy pertaining to icotinib duration were found in any of the subgroups. Rates of adverse events of grade 3 or higher were 8.3%, 5.9% and 2.4% for the 12-month icotinib, 6-month icotinib and observation groups, respectively. The safety profile remained similar to the previous reports for icotinib. Conclusions: Adjuvant icotinib for 12 months and 6 months provide a significant DFS and OS benefit compared with observation in patients with completely resected EGFR-mutated stage II-IIIA NSCLC with a manageable safety profile. Nevertheless, 12 months of icotinib had no additional benefit compared with 6 months. Clinical trial information: NCT01996098 .

Baseline (BL) characteristics and efficacy endpoints for patients (pts) with node-negative (N0) HR+/HER2− early breast cancer (EBC): NATALEE trial.

512 Background: NATALEE assessed ribociclib (RIB) + non-steroidal aromatase inhibitor (NSAI) vs NSAI alone in pts with HR+/HER2− EBC at increased risk of recurrence, including pts with N0 disease, and showed a statistically significant invasive disease-free survival (iDFS) benefit. We report BL characteristics, efficacy, and safety for the N0 subgroup. Methods: Pts with stage II/III HR+/HER2− EBC were randomized (R) 1:1 to RIB 400 mg/d (3 wk on/1 wk off for 36 mo) + NSAI (letrozole or anastrozole for ≥60 mo) or NSAI alone. Men and premenopausal women received goserelin. Pts could receive any standard (neo)adjuvant endocrine therapy (ET) ≤12 mo before randomization. In the intent-to-treat (ITT) population, 78% of pts completed 3y of RIB treatment (tx) or discontinued early with 21% still on tx at the time of this analysis (data cutoff: July 21, 2023; median follow up, 33 mo). The N0 subgroup included pts with T2N0 (stage IIA; with grade [G]3, or G2 disease and Ki-67 ≥20% or high genomic risk [HGR]), T3N0 (stage IIB), and T4N0 (stage IIIB); T1N0 was excluded. Results: Of 2549 pts R to RIB + NSAI and 2552 to NSAI alone, 285 (11%) and 328 (13%) had N0 disease, respectively. BL characteristics for the N0 subgroup were balanced across arms. Most pts were premenopausal (RIB + NSAI: 67% vs NSAI alone: 63%). Pts with N0 disease had anatomic stage IIA (RIB + NSAI: 74% vs NSAI alone: 73%), stage IIB (17% vs 13%), or stage IIIB (9% vs 12%) disease (Table). Most pts received prior chemotherapy (RIB + NSAI: 72% vs NSAI alone: 71%); prior ET was received by 59% vs 62% of pts with RIB + NSAI vs NSAI alone. For pts with T2N0 disease treated with RIB + NSAI vs NSAI alone, 49% vs 45% had G3 disease and 49% vs 53% had G2 disease (54% vs 56% with T2N0, G2 &amp; Ki-67 &gt; 20%; 13% vs 23% with T2N0, G2, Ki-67 ≤20%/missing &amp; HGR). Consistent with the ITT population, RIB + NSAI improved iDFS (HR, 0.72; 95% CI, 0.41-1.27; 3y rate with RIB + NSAI vs NSAI alone, 93.2% vs 90.6%), distant disease–free survival (DDFS; HR, 0.70; 95% CI, 0.38-1.29; 3y rate, 94.3% vs 91.5%), and distant recurrence–free survival (DRFS; HR, 0.58; 95% CI, 0.29-1.17; 3y rate, 96.3% vs 92.5%) in pts with high-risk N0 disease. The safety profile of RIB in the N0 subgroup was consistent with the ITT population. The rate of discontinuation due to all grade adverse events was 24% vs 8% with RIB + NSAI vs NSAI alone. Conclusions: This analysis showed a consistent efficacy benefit and manageable safety profile of RIB + NSAI vs NSAI alone in pts with N0 disease in NATALEE. The 3y iDFS, DDFS, and DRFS rates in the control arm at this early follow-up underscore the risk of recurrence for the N0 subgroup. These findings support the use of RIB in pts with HR+/HER2− EBC at increased risk of recurrence, including pts with N0 disease. Clinical trial information: NCT03701334 . [Table: see text]

Correlation of serum anti-Müllerian hormone (AMH) levels on identification of premenopausal patients (pts) with hormone receptor positive (HR+), HER2-negative, node-positive breast cancer most likely to benefit from adjuvant chemotherapy in SWOG S1007 (RxPONDER).

505 Background: SWOG S1007 was a phase 3 randomized trial to evaluate the benefit of endocrine therapy alone (ET) or with chemotherapy (CET) in pts with HR+/HER2- invasive breast cancer with recurrence score (RS) ≤ 25. There was no invasive disease-free survival (IDFS) benefit for CET compared to ET in postmenopausal women However, in premenopausal women CET had an IDFS improvement compared to ET (HR=0.60; 95% 0.43-0.83). The objective was to further refine patient subgroups who benefit from CET, we measured baseline hormone levels in S1007 pts to quantify their menstrual status by serum hormone levels and associated clinical outcomes. Methods: Serum estradiol (E), progesterone (P), follicular stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and inhibin B (IB) were assessed on baseline serum samples from 1,015 pts who self-reported being premenopausal and age &lt; 55. Magnetic fluorescent bead-based immunoassays ( i.e., Luminex assays) or colorimetric ELISAs were performed at the Biomarker Discovery Laboratory at the University of Kansas Medical Center to measure hormone levels. Associations of the markers (both continuous and dichotomized) with IDFS and distant relapse-free survival (DRFS) were tested for prognosis and prediction of CET benefit using Cox regression. Results: Single baseline measurement of IB, P, E, LH, FSH, or combination of E/LH/FSH, was not prognostic for IDFS or predictive for chemotherapy benefit. However, AMH levels (≥10 pg/mL) showed significant interaction with chemotherapy benefit (p=0.019), and risk increased with continuous AMH with ET alone, but not CET (p=0.03). Compared to ET alone, CET was beneficial in the 79% of premenopausal patients with AMH levels ≥10 pg/mL, a standard cutoff to define normal ovarian reserve (HR=0.48; 95% 0.33-0.69, adjusting for RS). CET was not beneficial in the 21% with AMH &lt; 10 (HR=1.21; 95% 0.60-2.43). Absolute 5-year IDFS benefit of CET for RS ≤ 25 was 7.8% (95.2%-87.4%) for AMH ≥ 10 vs. -1.7% (89.1%-90.8%) for AMH &lt; 10. DRFS showed a similar pattern with CET benefit in AMH ≥10 pg/mL (5-year DRFS benefit: 4.4%; HR=0.41; 95% 0.25-0.68, adjusting for RS) and no benefit in AMH &lt; 10 (5-year DRFS benefit: -0.9%, HR=1.50; 95% 0.62-3.63). Conclusions: Among self-reported premenopausal patients &lt; age 55, pts with baseline serum AMH levels ≥10 pg/mL showed significant benefit from CET compared to patients with AMH levels &lt;10 pg/mL. AMH levels were a better indicator of CET benefit than self-reported menopause status, age, or E/LH/FSH levels. Use of AMH-based selection of patients may inform who most benefits from the addition of adjuvant chemotherapy to ET. Clinical trial information: NCT01272037 .

Real-world (RW) risk of recurrence among patients (pts) diagnosed with stage II-III HR+/HER2− early breast cancer (EBC) treated with endocrine therapy (ET) in the US.

e12533 Background: Despite improved management of HR+/HER2− EBC, pts experience recurrences while on or up to decades after ending standard-of-care (SOC) ET. Addition of adjuvant (adj) cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), ribociclib and abemaciclib, to SOC ET resulted in significant improvement of outcomes in pts with HR+/HER2− EBC at risk of recurrence. In NATALEE, ribociclib showed invasive disease-free survival (iDFS) benefit in a broader population, including select node-negative (N0) disease. This RW study describes short-term recurrence in pts with HR+/HER2− stage II-III EBC treated with SOC adj ET ± chemotherapy (CT) in the last decade in the US, prior to use of adj CDK4/6is. Methods: A medical record review from large academic (Memorial Sloan Kettering Cancer Center) and community (Tennessee Oncology) oncology practices was conducted. Adult women with stage II-III HR+/HER2− BC (AJCC 8) who underwent surgical resection and initiated adj ET between Jan 2012 and Dec 2018 were included. Pts were randomly selected for equal distribution by year of adj ET initiation. Study measures were summarized descriptively. Kaplan-Meier method was used to estimate 3-, 5-, and 7-y iDFS and distant disease–free survival (DDFS). Results: Medical charts of 992 pts were analyzed (median follow-up from initiation of adj ET, 6.3 y). Median age was 58 y. Most pts (76.7%) had stage II disease at diagnosis, 64.0% received CT, and 34.2% were premenopausal. In total, 35.8% of pts were N0. Among all N0 pts, ≈41.4% had high-risk tumor features, as defined by NATALEE: &gt;5 cm, 9.3%; 2-5 cm with G3, 25.9%; 2-5 cm with G2 + high genomic risk, estimated at 6.2%. N1(1-3) and N2/N3 (≥4) involvement was seen in 46.8% and 17.4% of pts, respectively. Analyses of iDFS/DDFS showed cumulative risk of invasive disease recurrence, predominantly distant disease, over 7 y in 21.4% across all stage II/III pts and 25.7% among the N0 pts meeting NATALEE criteria. Conclusions: This RW analysis from 2 major academic and community centers in the US confirms pts with stage II-III HR+/HER2− EBC, including select pts with N0 disease, experience considerable risk of recurrence, as early as during the adj treatment period cumulating over time. These findings warrant the consideration for tolerable treatment escalation for pts with stage II-III HR+/HER2− EBC.

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

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

Overall survival analysis of first line CDK4/6 inhibitors in a large real-world cohort of patients with hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer.

e13095 Background: Multiple clinical trials have demonstrated the efficacy of the commercially available CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) as upfront therapy in patients (pts) with (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Recently, differences in overall survival (OS) benefit in MBC and invasive disease-free survival benefit in early-stage BC suggest greater potency of abemaciclib and ribociclib compared to palbociclib. Here we report a comprehensive OS analysis of a cohort of pts with HR+/HER2- MBC treated with ribociclib, palbociclib or abemaciclib and ET in 1st line setting. Methods: We retrieved medical records of pts with HR+/HER2- MBC receiving CDK4/6i as 1st line therapy between December 2013 and October 2023 at Memorial Sloan Kettering Cancer Center. We investigated the impact of clinico-pathological characteristics and treatment type as categorical variables on OS using uni- and multivariate Cox (proportional hazard) regression model. Any p-value (p) &lt;0.05 was deemed to be statistically significant. Results: 854 pts were included in the analysis, 838 females (98%) and 16 males at birth. The median age was 56 (IQR: 48-65). Overall, 722 (84%) pts received palbociclib, 88 (11%) abemaciclib, and 44 (5%) ribociclib. Most pts received aromatase inhibitor (AI) as ET backbone (n=634, 74%); 214 received fulvestrant (35%), and 6 received tamoxifen (1%). After a median follow-up of 3.14 years (range: 1.7-4.6), the median OS of the full cohort was 54.7 months (95%CI: 50-63.1). Clinico-pathological characteristics that resulted independently associated with worse OS were: male gender at birth (HR:2, 95%CI:1.4-4), disease-free interval ≤ 2 years (HR:1.64, 95%CI:1.11-2.44), ER-low status (HR: 2.27, 95%CI:1.42-3.63), high grade(HR: 1.28, 95%CI:1.01-1.62), liver involvement (HR: 1.48, 95%CI:1.08-2.03), and number of disease sites &gt;3 (HR:1.35, 95%CI:1.03-1.78). HER2-low status was associated with better OS (HR: 0.75, 95%CI:0.59-0.96). In terms of type of treatment, there was a trend toward improved OS in patients receiving AI rather than fulvestrant or tamoxifen (HR:0.76, 95%: 0.58-1), while the type of CDK4/6i did not affect the outcome. Conclusions: Clinical parameters of early relapse, high disease burden, and intrinsic tumor aggressiveness seem to be the main drivers of poor prognosis in patients with HR+/HER2- MBC in 1st line setting. In this analysis, type of CDK4/6i did not have a significant impact on OS, although pts treated with abemaciclib and ribociclib were underrepresented in the cohort due to the earlier and prevalent use of palbociclib as the first-in-class FDA-approved CDK4/6i. These data are reassuring about the use of palbociclib suggesting that a switch of CKD4/6i is not needed in pts with ongoing treatment and demonstrated benefit.

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

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