Oncology Group Research Articles

Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment

ObjectivesOn the basis of the positive results of CheckMate-743, first-line (1L) treatment of malignant pleural mesothelioma (MPM) with the combination of ipilimumab and nivolumab (ipi/nivo) has become a standard-of-care. Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi/nivo on the basis of MAPS2 results. Here we report on real-world survival and safety outcomes of ipi/nivo for patients with MPM in Switzerland. MethodsTwelve cancer centers contributed data to this retrospective cohort. Baseline characteristics including age, sex, histology, programmed death-ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous/subsequent therapies were collected. The efficacy and safety outcomes were assessed by local investigators. ResultsOf the 109 patients with MPM treated with ipi/nivo between November 2017 and March 2023 (median follow-up of 16.6 months) 75% had epithelioid, 9% biphasic, and 16% sarcomatoid histology. The median age was 72 years; 91% were males, and 83% had an ECOG PS of 0 to 1. Ipilimumab in combination with nivolumab was given as 1L in 43% and as 2L+ treatment in 57% of patients. The objective response rate was 21% in 1L and 15% in 2L+. Median progression-free survival was 6.5 and 2.8 months, respectively. Median overall survival (OS) from the start of ipi/nivo was 12.6 months for 1L and 6.9 months for 2L+. No differences in OS were observed depending on age and programmed death-ligand 1 expression. Nevertheless, the median OS was significantly worse in patients with an ECOG PS of 2 or higher than those with an ECOG PS of 0 to 1 (2.4 versus 11.9 months, p < 0.001). Treatment-related adverse events (TRAEs) of any grade related to ipi/nivo treatment occurred in 65 patients (62%). The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients. ConclusionIn this real-world cohort of patients with MPM treated with ipi/nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.

O5-2 WJOG (West Japan Oncology Group) Breast Cancer Consensus Meeting 2023

O5-2 WJOG (West Japan Oncology Group) Breast Cancer Consensus Meeting 2023

Longitudinal Health-Related Quality of Life Among Patients With High-Risk Pediatric Hodgkin Lymphoma Treated on the Children's Oncology Group AHOD 1331 Study.

PURPOSEThere have been no previous longitudinal assessments of health-related quality of life (HRQoL) during treatment for pediatric Hodgkin lymphoma (HL). The addition of brentuximab vedotin (BV) to a multidrug chemotherapy backbone demonstrated superior efficacy to standard chemotherapy for patients with pediatric high-risk HL in the AHOD 1331 trial. However, the impact on HRQoL is unknown.PATIENTS AND METHODSAfter treatment random assignment, 268 participants older than 11 years were enrolled in a prespecified, longitudinal, patient-reported outcomes substudy. HRQoL was assessed using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale before treatment (T1) and at cycle 2 (T2), cycle 5 (T3), and end of treatment (T4). A clinically meaningful increase in HRQoL was considered 7 points on the CHRIs-Global. Multivariable linear regression estimated associations between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated changes in HRQoL across the treatment arm.RESULTSParticipant characteristics were balanced by treatment arm. Ninety-three percent of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 77% at T4. At T1, female sex and fever (P < .05) were each associated with worse HRQoL. By T2, participants in the BV arm experienced a statistically and clinically significant improvement in HRQoL (β = 7.3 [95% CI, 3.2 to 11.4]; P ≤ .001), which was greater than the change in the standard arm (difference in change β = 5.1 [95% CI, -0.2 to 10.3]; P = .057). The standard arm did not experience a statistically or clinically significant increase in HRQoL until T4 (β = 9.3 [95% CI, 4.7 to 11.5]; P < .001).CONCLUSIONThese data demonstrate successful collection of serial HRQoL from youth with high-risk pediatric HL and improvement in HRQoL over the course of initial therapy, sooner and to a greater extent in the group receiving the novel agent BV.

The role of Cabazitaxel in patients with castration-resistant and osseous metastases prostate cancer. A Hellenic Cooperative Oncology Group Phase II Study.: Cabazitaxel in mCRPC patients with osseous metastases

BackgroundCabazitaxel is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC) patients previously exposed to docetaxel and novel hormonal treatments. Understanding the molecular biology of mCRPC disease and taking into account the several approved treatment options, biomarkers are needed to guide decision making including cabazitaxel treatment. MethodsCababone was a phase II translational study that attempted to identify predictors of cabazitaxel efficacy. mCRPC with documented bone metastases were enrolled prospectively and treated with cabazitaxel 25mg/m2 every three weeks. Prostate cancer biopsies, bone marrow aspirates and blood samples were collected for translational research. ResultsSixty patients were enrolled and 59 received treatment according to protocol. Six-month progression free survival (PFS) rate was 47% (95% CI: 33% - 59%) and 12-month Overall Survival (OS) rate was 70% (95% CI: 56% - 80%). Patients with reactive hematopoiesis had improved PFS and OS with cabazitaxel treatment. Mutations in HRR genes were detected in 7 patients. ConclusionsNo differences in cabazitaxel efficacy were noted according to mutational status of HRR genes analyzed. No new safety issues were detected. In conclusion, CabaBone confirmed efficacy of cabazitaxel in mCRPC patients including the subgroup of patients with HRR mutations. Reactive hematopoiesis in bone marrow biopsies was related to improved survival warranting further investigation of bone biomarkers as predictors of cabazitaxel efficacy. Micro-AbstactCabaBone is a phase II translational study that evaluated the role of bone microenvironment and HRR genes mutations in the efficacy of cabazitaxel in mCRPC patients with bone-only disease. Study confirmed efficacy of cabazitaxel in patients independent of the presence of HRR gene mutations. Reactive hematopoiesis in bone marrow was recognized as a possible predictive and prognostic biomarker of cabazitaxel efficacy.

Posterior aggressive debulking versus minimal decompression surgery in patients with metastatic spinal cord compression: propensity-score-matching analysis from a multicenter study cohort.

The goal of this study was to evaluate the comparative outcomes of aggressive debulking (AD) and minimal decompression (MD) surgeries for metastatic spinal cord compression based on surgical burden, functional improvement, and symptomatic local recurrence (SLR). In this retrospective analysis from 2 tertiary hospitals, the authors assessed patients with metastatic spinal cord compression treated via AD and MD surgeries between 2010 and 2022. The evaluation included patient demographics, Eastern Cooperative Oncology Group performance status (ECOG-PS), primary tumor type, modified Tokuhashi scores, surgical burden, and SLR. Propensity-score matching (1:1 ratio) was conducted based on oncological status for intergroup comparisons. Survival analysis and logistic regression analyses were conducted. A total of 264 patients were included in the study. After 1:1 propensity-score matching, a total of 156 matched patients were analyzed (78 patients each in the AD and MD groups). Operation time, estimated blood loss, transfused red blood cell units, and inpatient medical complications were significantly higher in the AD group compared to the MD group (p = 0.001, p = 0.002, p = 0.006, and p = 0.035, respectively). There was no significant difference in distribution of postoperative ECOG-PS between the AD and MD groups (OR 1.461, 95% CI 0.821-2.599, p = 0.197). In initially nonambulatory patients (ECOG-PS of grade 3 or 4), the AD group showed a higher proportion of patients regaining ambulatory function compared to the MD group (56.5% vs 36.2%; OR 2.294, p = 0.049). In cases with a preoperative ECOG-PS of grade 3, the difference in ambulation recovery between AD and MD was not statistically significant (60.0% vs 53.3%, p = 0.577). However, for severely impaired patients (ECOG-PS of grade 4), the AD group showed a higher proportion of patients regaining ambulatory function compared to the MD group (33.3% vs 5.9%, p = 0.086). Symptomatic SLR-free survival showed no significant differences at final follow-up (p = 0.095). Multivariate analysis identified the modified Tokuhashi score as the sole predictor of SLR (OR 1.871, p = 0.001). This study found that MD surgery significantly reduced surgical burden compared to AD. AD surgery led to slightly better functional recovery showing greater rescue ratios, especially in patients with a preoperative ECOG-PS of grade 4. However, no difference in rescue ratio was observed in patients with a preoperative ECOG-PS of grade 3. There was no significant difference in SLR rates between the AD and MD groups.

Outcomes and prognostic factors in 3306 patients with relapsed/refractory chronic lymphocytic leukemia treated with ibrutinib outside of clinical trials: A nationwide study.

We performed a cohort study that included all patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who received ibrutinib in the Italian National Health Service. With a median follow-up of 42.2 months (IQR 30.8-54.6 months), the study involved 3306 patients with a median age of 72.1 years, of whom 42.6% had received ≥2 previous lines of treatment. The estimated 24-month probabilities of being on treatment and alive were 57.9% (95% confidence interval [CI]: 59.6-56.2) and 76.6% (95% CI: 75.2-78.1), respectively. The median time to treatment discontinuation (TTD) was 31.3 months (95% CI: 29.5-33.5). Out of 3306 patients, 2015 (60.9%) discontinued treatment, with 993 cases attributed to death or disease progression (30.0% of all cases). Among the 1022 patients who discontinued treatment for reasons other than progression or death, 564 (17.1%) patients did so due to toxicity or medical decision, while 458 patients (13.8%) were lost to follow-up. Multivariable analysis revealed that age, Eastern Cooperative Oncology Group Performance Status, the number of previous lines of therapy, refractoriness to the last treatment, and reduced renal function were associated with shorter TTD and overall survival (OS). The coexistence of 17p- and TP53 mutations had an independent unfavorable impact on TTD and OS. Nonstandard doses were associated with shorter TTD and advanced stage with shorter OS. The median OS postprogression and postdiscontinuation for other reasons were estimated at 12.9 (95% CI: 11.3-16.2) and 22.7 months (95% CI: 20.2-28.3), respectively. This large real-world study shows that ibrutinib is an effective treatment for R/R CLL. Baseline patient characteristics and double-hit TP53 aberrations were associated with inferior prognosis, and discontinuation due to CLL progression portended a poor outcome.

Response to platinum-based therapies in second-line after immunotherapy in advanced or metastatic non-small-cell lung cancer PD-L1 ≥50.

Platinum-based therapies for patients with advanced non-small-cell lung cancer (NSCLC) have classically provided overall survival (OS) rates of six to nine months and objective response rates (ORRs) of 20-30%. Whether prior immunotherapy determines a different response to platinum is currently unknown. This study aimed to analyse the current response characteristics to platinum as a second-line treatment for advanced NSCLC (PD-L1 ≥50%) after first-line immunotherapy. This retrospective study was conducted at the University Hospital of Salamanca (CAUSA) between 2016 and 2023 with patients who had advanced NSCLC (PD-L1 ≥50%) treated with second-line platinum-based therapies after immunotherapy (without mutations in EGFR, ALK or ROS1 and with Eastern Cooperative Oncology Group (ECOG) ≤1 during the first- and second-line treatments). Survival and response correlation analyses (Kaplan-Meier and log rank tests in SPSS v. 25) were performed. Subsequently, the results were compared with historical cohorts (PubMed, COCHRANE, ScienceDirect, Embase, and the clinical trial registry) who had received platinum-based therapies for advanced NSCLC. Seventeen patients were analysed (11 male and 6 female). Their median age was 67 years (interquartile range, 50-77 years). Fifteen patients (88.2%) were smokers or former smokers. The patients' main histology was adenocarcinoma (9 patients, 52.9%). All first-line treatments applied pembrolizumab (median dose: 12 cycles). Second-line platinum-based therapy achieved OS of 25 months (95% CI: 7-45 months) and progression-free survival (PFS) of 6 months (95% CI: 2.5-95 months). The ORR was 47.1% [seven patients with a partial response (PR) and one patient with a complete response (CR)]. Of the patients with PRs or CRs, 75% were treated with platinum plus pemetrexed. The one-year survival rate was 58.8%. The historical OS for first-line platinum-based doublets is 7 to 12 months, with PFS of three to five months and an ORR of 17-30%. The current response to second-line platinum-based therapies for patients with advanced NSCLC after immunotherapy appears to achieve favourable response rates and be an optimal treatment after progression to immunotherapy. Prior immunotherapy appears to enhance these patients' platinum response, though future confirmatory studies are necessary.

Phase II study of ramucirumab and docetaxel for previously platinum-treated patients with non-small cell lung cancer and malignant pleural effusion (PLEURAM study).

The prognosis of patients with lung cancer and malignant pleural effusion (MPE) caused by carcinomatous pleurisy is poor. Chemical pleurodesis is commonly performed clinically, however, often has a high failure rate. Furthermore, prolonged sustained drainage and delayed introduction of systemic chemotherapy could increase the risk of worsening the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in the treatment of patients with non-small cell lung cancer (NSCLC). Therefore, both systemic and local treatments are crucial to control MPE. Ramucirumab, an antibody targeting vascular endothelial growth factor receptor 2, is expected to be effective for treatment of MPE. However, there are no data supporting this hypothesis. Herein, we performed a prospective phase II study to evaluate the efficacy and safety of ramucirumab plus docetaxel in NSCLC patients with MPE. A single-arm phase II study was conducted to elucidate the efficacy and safety of ramucirumab plus docetaxel as a combined treatment for patients NSCLC and MPE previously treated with platinum-based chemotherapy. The primary endpoint was the MPE control proportion at eight weeks after protocol treatment initiation. The secondary endpoints of the study were objective response rate (ORR), progression-free survival (PFS), one-year survival rate, overall survival (OS), and toxicity profile. Between September 2019 and March 2022, 15 patients were enrolled. The pleural effusion control proportion at eight weeks was 100% [90% confidence interval (CI): 84.0-100%, and 95% CI: 78.4-100%], and the primary endpoint of this study was met. The ORR was 6.7% (95% CI: 0.2-32.0%), the median PFS was 6.3 months (95% CI: 1.9-6.9), and the median OS was 10.4 months (95% CI: 3.2-16.5). No Grade 5 or unexpected adverse events were observed. Ramucirumab plus docetaxel is a promising and safe treatment option for previously treated patients with NSCLC and MPE, showing a high pleural effusion control rate.

Real-world outcomes among patients with advanced EGFRm NSCLC previously treated with osimertinib and platinum-based chemotherapy.

396 Background: For patients with advanced EGFR-mutant non-small cell lung cancer (EGFRm aNSCLC) progressing after osimertinib (OSI) and platinum-based chemotherapy (PBC) no uniformly accepted standard of care exists. The study was to provide updated results with a refreshed dataset for a previous study describing clinical outcomes of treatment regimens initiated after OSI and PBC in real-world patients with similar baseline characteristics to those in HERTHENA-Lung01 (HL-01), a multinational single-arm phase II trial evaluating the safety and efficacy of patritumab deruxtecan [1] . Methods: This study analyzed data from the US nationwide Flatiron Health electronic health record–derived aNSCLC de-identified database from approximately 280 US cancer clinics (~800 sites of care). Adult patients with an aNSCLC diagnosis (after 01 January 2011) and prior treatment with OSI and PBC, who initiated a subsequent line of therapy (index LOT) before 01 August 2022 were included in the study. Patients were chosen to closely match the HL-01 eligibility criteria (documented exon 19 deletion or L858R mutation; Eastern Cooperative Oncology Group Performance Status of 0 or 1; and absence of relevant comorbidities at index date). To further balance patient characteristics, the sample was propensity-score (PS) weighted based on nine covariates. Real-world overall survival (rwOS), progression-free survival (rwPFS) and overall response (rwORR, defined as partial or complete response with ≥2 assessments ≥28 days apart) were assessed from the start of the index LOT with corresponding 95% confidence intervals (CI). Results: 179 patients in the database fulfilled the eligibility criteria, increasing the sample size by 42% compared to the previous study 1 . Median age of the unweighted sample at index was 68 years, 65.9% of patients were female, 40.2% had a history of smoking and 26.3% received more than 3 LOTs prior to the index LOT. In the PS-weighted cohort (standard mean difference of all covariates was ≤0.127) the median rwOS was 9.1 months (95% CI: 7.3 – 11.3) and median rwPFS was 3.5 months (95% CI: 2.7 – 4.6). For a subsample of 75 patients with qualifying response assessments, rwORR was 12.7% (95% CI: 4.8 – 25.7). Conclusions: These observations in patients with EGFRm NSCLC after OSI and PBC demonstrate a limited clinical benefit with currently available therapies. The results are consistent with the previously published study and increase precision of the outcome estimates 1 . They highlight the high unmet need and provide further context on clinical outcomes of HL-01 trial results. [1] Patel et al. Clinical Outcomes of Real-World Treatment for Metastatic EGFRm NSCLC after Osimertinib and Platinum-Based Chemotherapy. 2023 Sep 9-12 Singapore. P2.31.

Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study.

Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma. VALENTINE-PTCL01 was a multicentre, open-label, single-arm, phase 2 trial performed at 47 hospitals in 12 countries across Asia, Europe, North America, and Oceania. Patients with either peripheral T-cell lymphoma or adult T-cell leukaemia/lymphoma, aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2 received oral valemetostat at 200 mg per day in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint for patients with peripheral T-cell lymphoma was the CT-based objective response rate by blinded independent central review (BICR) using 2014 Lugano response criteria. Patients who received valemetostat and had a confirmed eligible peripheral T-cell lymphoma subtype on central review were included in the efficacy analysis. The primary endpoint for patients with adult T-cell leukaemia/lymphoma was the safety and tolerability of valemetostat. Safety in both cohorts was assessed in all patients who received at least one dose of valemetostat. The trial is registered with ClinicalTrials.gov, NCT04703192, and EudraCT, 2020-004954-31, and is closed to enrolment. Between June 16, 2021, and Aug 10, 2022, 133 patients with relapsed or refractory peripheral T-cell lymphoma (median age 69·0 years [IQR 58·0-74·0]; 91 [68%] were male, and 42 [32%] were female) and 22 patients with adult T-cell leukaemia/lymphoma (66·5 years [54·0-73·0]; 15 [68%] were male, and seven [32%] were female) were enrolled. The median follow-up time was 12·3 months (95% CI 11·8-13·8). 52 (44%; 95% CI 35-53) of 119 efficacy-evaluable patients with relapsed or refractory peripheral T-cell lymphoma had an objective response. The most common grade 3-4 adverse events were thrombocytopenia (31 [23%] of 133 patients in the peripheral T-cell lymphoma group and 11 [50%] of 22 patients in the adult T-cell leukaemia/lymphoma group), anaemia (25 [19%] and ten [46%]), and neutropenia (23 [17%] and four [18%]). Serious treatment-emergent adverse events were reported in 53 (40%) patients with peripheral T-cell lymphoma and 15 (68%) patients with adult T-cell leukaemia/lymphoma; nine (7%) patients and one (5%) patient had a serious treatment-emergent adverse event considered to be treatment related, respectively. No treatment-related deaths were reported. These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile. Daiichi Sankyo.

Patient- and Areal-Level Risk Factors Associated With Lung Cancer Mortality in Victoria, Australia: A Bayesian Spatial Survival Analysis.

In Australia, lung cancer is the leading cause of cancer-related deaths. In Victoria, the mortality risk is assumed to vary across Local Government Areas (LGAs) due to variations in socioeconomic advantage, remoteness, and healthcare accessibility. Thus, we applied Bayesian spatial survival models to examine the geographic variation in lung cancer survival in Victoria. Data on lung cancer cases were extracted from the Victorian Lung Cancer Registry (VLCR). To account for spatial dependence and risk factors of survival in lung cancer patients, we employed a Bayesian spatial survival model. Conditional Autoregressive (CAR) prior was assigned to model the spatial dependence. Deviance Information Criterion (DIC), Watanabe Akaike Information Criterion (WAIC), and Log Pseudo Marginal Likelihood (LPML) were used for model comparison. In the final best-fitted model, the Adjusted Hazard Ratio (AHR) with the 95% Credible Interval (CrI) was reported. The outcome variable was the survival status of lung cancer patients, defined as whether they survived or died during the follow-up period (death was our interest). Our study revealed substantial variations in lung cancer mortality in Victoria. Poor Eastern Cooperative Oncology Group (ECOG) performance status, diagnosed at a regional hospital, Small Cell Lung Cancer (SCLC), advanced age, and advanced clinical stage were associated with a higher risk of mortality, whereas being female, presented at Multidisciplinary Team (MDT) meeting, and diagnosed at a metropolitan private hospital were significantly associated with a lower risk of mortality. Identifying geographical disparities in lung cancer survival may help shape healthcare policy to implement more targeted and effective lung cancer care services.

Improvements in Children’s Oncology Group neuroblastoma risk stratification through a change in age cut-off and use of INRGSS

Improvements in Children’s Oncology Group neuroblastoma risk stratification through a change in age cut-off and use of INRGSS

Health-related quality of life of Canadian patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.

397 Background: The EuroQol 5 Dimension 5 Level (EQ-5D-5L) is a validated tool that assesses health utility (HU) as a self-reported measure of health-related quality of life (HRQoL). This study aims to generate Canadian-specific HU data for patients with stable, HER2-positive (HER2+) metastatic breast cancer (mBC) receiving standard therapies. Methods: A cross-sectional study was conducted at McGill University Health Centre in Quebec, Canada. Eligibility criteria included: age ≥18 years, de novo or recurrent mBC, stable disease, and active treatment with a Health Canada-approved systemic therapy regimen (any line/time point on treatment). The EQ-5D-5L questionnaire was administered at every visit and each record was treated as a unique singular data point. The HU values were derived using the Canadian algorithm developed by Xie et al., 2016. The EQ-5D-5L measures HRQoL across five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and is scored on 5 levels ranging from one “no problems” to five “extreme problems”. A second part of the questionnaire includes a visual analogue scale (VAS) where respondents rank their overall health on scale of 0-100. The primary outcome was mean HU and standard deviation (SD) for HER2+ patients overall. Secondary outcomes included mean HU by hormone receptor (HR) status and describing patient responses to the questionnaire. Results: Between December 2022 and July 2023, a total of 81 HER2+ HU data points were included for analysis, representing 30 patients. For these patients, the mean age was 54.2 years (SD: 10.6). Most patients (58.3%) were on first line and had an Eastern Cooperative Oncology Group Performance Status of 0 (65.5%). The mean HU value was 0.83 (SD: 0.14, n=81). For patients with HR-positive mBC, the mean HU was 0.81 (SD: 0.14, n=44), while for patients with HR-negative mBC, it was 0.85 (SD: 0.13, n=37). The majority of patients reported “no problems” across all domains: mobility (69.1%), self-care (81.5%), usual activities (46.9%), pain/discomfort (35.8%), and anxiety/depression (58%). The mean VAS score was 77.3 (SD: 17.0). Conclusions: This study provides the first Canadian data on contemporary HU values for patients with HER2+ mBC, which reflects current HRQoL amidst a changing treatment landscape.

Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial

Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit. NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m2) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial. Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported. Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC. Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union.

Nivolumab plus ipilimumab versus carboplatin-based doublet as first-line treatment for patients with advanced non-small-cell lung cancer aged ≥70 years or with an ECOG performance status of 2 (GFPC 08-2015 ENERGY): a randomised, open-label, phase 3 study.

Combined treatment with anti-PD-1 and anti-CTLA-4 antibodies has shown superiority over chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC), but data for older patients (aged ≥70 years) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or those with an ECOG performance status of 2 are scarce. We aimed to test the superiority of the PD-1 antibody nivolumab and the CTLA-4 antibody ipilimumab over platinum-based doublet chemotherapy as first-line treatment in patients with NSCLC aged 70 years or older or with an ECOG performance status of 2. This open-label, multicentre, randomised, controlled, phase 3 trial was done at 30 hospitals and cancer centres in France. Eligible patients had stage IV histologically proven NSCLC, with no known oncogenic alterations, and were either aged 70 years or older with ECOG performance status of 0-2 or younger than 70 years with an ECOG performance status of 2. Patients were randomly assigned (1:1) centrally, using a computer-generated algorithm stratified by age (<70 vs ≥70 years), ECOG performance status (0-1 vs 2), and histology (squamous vs non-squamous) to receive nivolumab plus ipilimumab or platinum-based doublet chemotherapy (carboplatin [area under the curve ≤700 mg] plus pemetrexed [500 mg/m2 intravenous infusion every 3 weeks] or carboplatin [on day 1; area under the curve ≤700 mg] plus paclitaxel [90 mg/m2 as intravenous infusion on days 1, 5, and 15, every 4 weeks]). The primary endpoint was overall survival; secondary endpoints included progression-free survival and safety. All efficacy analyses were performed in the intention-to-treat population, which included all randomly assigned patients. Safety was analysed in the safety analysis set, which included all randomly assigned patients who received at least one dose of study treatment and who had at least one safety follow-up. The trial is registered with ClinicalTrials.gov, NCT03351361. The trial was stopped early for futility on the basis of a pre-planned interim analysis after 33% of the expected events had occurred. Between Feb 12, 2018, and Dec 15, 2020, 217 patients were randomly assigned, of whom 216 patients were included in the final analysis, with 109 patients in the nivolumab plus ipilimumab group and 107 in the chemotherapy group; median age was 74 years (IQR 70-78). Median overall survival was 14·7 months (95% CI 8·0-19·7) in the nivolumab plus ipilimumab group and 9·9 months (7·7-12·3) in chemotherapy group (hazard ratio [HR] 0·85 [95% CI 0·62-1·16]). Among patients aged 70 years or older with an ECOG performance status of 0-1 (median age 76 years [IQR 73-79]), median overall survival was longer in the nivolumab plus ipilimumab group than the chemotherapy group: 22·6 months (95% CI 18·1-36·0) versus 11·8 months (8·9-20·5; HR 0·64 [95% CI 0·46-0·96]). Among patients with an ECOG performance status of 2 (median age 69 years [IQR 63-75]), median overall survival was 2·9 months (95% CI 1·4-4·8) in the nivolumab plus ipilimumab group versus 6·1 months (3·5-10·4) in the chemotherapy group (HR 1·32 [95% CI 0·82-2·11]). No new safety signals were reported. The most frequent grade 3 or worse adverse events were neutropenia (28 [27%] of 103 patients) in the chemotherapy group and endocrine disorders (five [5%] of 105 patients), cardiac disorders (ten [10%] patients), and gastrointestinal disorders (11 [11%] patients) in the nivolumab plus ipilimumab group. The study showed no benefit of nivolumab plus ipilimumab combination in the overall study population. As a result of early stopping, the trial was underpowered for primary and secondary endpoints; however, the finding of better survival with nivolumab plus ipilimumab compared with platinum doublet in the subgroup of older patients with NSCLC with an ECOG performance status of 0-1 warrants further study. Bristol-Myers Squibb.

Boosting Antioxidant Defense: The Effect of Astaxantin on Superoxidase Dismutase and Malondialdehyde Reduction in Patients with Head and Neck Cancer Receiving Cisplatin Chemotherapy.

Background: Superoxide dismutase (SOD) can be decreased and malondialdehyde (MDA) can be increased in patients with head and neck cancer (HNC) as a result of reactive oxygen species (ROS) brought on by cisplatin. Astaxanthin is one of the external antioxidants required to combat ROS by raising SOD and lowering MDA. The purpose of this study is to demonstrate that astaxanthin can raise SOD and lower MDA in patients with HNC caused by cisplatin. Methods: 42 research subjects were randomly assigned to two groups in a double-blind, randomized controlled trial pre-post test design. Astaxanthin 4 mg BID was administered to the treatment group, whereas a single dosage of 500 mg of vitamin C and 250 mg of vitamin E IU was given to the control group. According to the Mann Whitney test, if p < 0.05, there is a significant difference in the delta of the decrease in SOD and MDA levels between the astaxanthin and vitamin C & E groups. Results: There were 42 research subjects, with a mean age of 48.2 years, a 2:1 male to female ratio, 23 (54.8%) with nasopharyngeal cancer, 32 (76.2%) with stage IV, 14 (33.3%) with cycle IV, 24 (57.1%) with paclitaxel-Cisplatin, 31 (73.8%) with Eastern Cooperative Oncological Group (ECOG) I, and 31 (73.8%) with Normal Body Mass Index. While there was a substantial drop in MDA (p=0.000), there was no significant difference in the delta reduction in SOD (p=0.443). Conclusion: Patients with HNC who receive cisplatin chemotherapy can have an increase in SOD and a decrease in MDA after receiving astaxanthin for 21 days.

Pembrolizumab plus chemotherapy for advanced and recurrent cervical cancer: final analysis according to bevacizumab use in the randomized KEYNOTE-826 study

In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (± bevacizumab) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer. This exploratory analysis examined outcomes in patient subgroups defined by bevacizumab use. Eligible adult patients had persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix not previously treated with chemotherapy and not amenable to curative treatment; measurable disease per RECIST v1.1; and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1:1 to pembrolizumab 200 mg every 3 weeks or placebo for up to 35 cycles plus chemotherapy (± bevacizumab 15 mg/kg). Dual primary endpoints were OS and PFS per RECIST v1.1 by investigator assessment. Outcomes were assessed in subgroups defined by bevacizumab use. Hazard ratios (HRs) and 95% CIs were based on a stratified Cox regression model. 617 patients were randomized (pembrolizumab arm, n=308 [63.6% with bevacizumab]; placebo arm, n=309 [62.5% with bevacizumab]). The most common reason for bevacizumab exclusion was medical contraindication (75.9%). Among patients who received bevacizumab, HRs (95% CIs) for PFS favored the pembrolizumab arm in the PD-L1 combined positive score (CPS) ≥1 (0.56 [0.43-0.73]) and all-comer (0.57 [0.45-0.73]) populations; OS results were 0.60 (0.45-0.79) and 0.61 (0.47-0.80), respectively. Among patients who did not receive bevacizumab, HRs (95% CIs) for PFS also favored the pembrolizumab arm in the PD-L1 CPS≥1 (0.61 [0.44-0.85]) and all-comer (0.69 [0.50-0.94]) populations; OS results were 0.61 (0.44-0.85) and 0.67 (0.49-0.91), respectively. Among patients who received bevacizumab, grade ≥3 treatment-related adverse events occurred in 74.0% of patients in the pembrolizumab arm and 66.8% in the placebo arm. Pembrolizumab plus chemotherapy prolonged PFS and OS and had manageable safety compared with placebo plus chemotherapy in patient subgroups defined by bevacizumab use.

Medical Oncology Group of Australia Incorporated Annual Scientific Meeting Program and Abstracts 14th-16th August 2024.

Medical Oncology Group of Australia Incorporated Annual Scientific Meeting Program and Abstracts 14th-16th August 2024.

Building an Effective International Medical Evacuation Program for Ukrainian Patients With Cancer Amid Prolonged Military Conflict.

During military conflicts, the immediate response to a severely disrupted health care system often overlooks the needs of patients with cancer who require continuous specialized care. The full-scale Russian invasion of Ukraine in February 2022 was no exception, leaving many Ukrainian patients without access to essential care. We conducted a retrospective cohort study to assess the impact of the MedEvac program, facilitating the transfer of Ukrainian patients with cancer to European Union (EU) institutions for treatment, and to describe its components. Patient data from the Ministry of Health of Ukraine (MOH) database (April 2022-April 2023) were analyzed. Of 639 applications in the MOH database, 339 (53.1%) had sufficient data for analysis and, of those, 281 (82.9%) were evacuated to EU hospitals. Median age of evacuated patients was 47 (IQR, 38-58) years and most were newly diagnosed (94.0%, n = 264). Predominantly, patients were evacuated for systemic cancer therapy (81.9%, n = 230). Multivariate logistic regression analysis revealed that a good performance status (Eastern Cooperative Oncology Group 0-2) was the most significant factor associated with evacuation (odds ratio [OR], 9.64 [95% CI, 3.08 to 30.23]). Patients with melanoma were more likely to be evacuated, even after adjustment for performance status (OR, 2.56 [95% CI, 1.14 to 5.72]), while patients with head and neck cancer were significantly less so (OR, 0.20 [95% CI, 0.06 to 0.72]). MedEvac program provides a viable model for medical evacuation and management of patients with cancer amid prolonged military conflict, highlighting the importance of international cooperation and setting a precedent for other crisis responses. Continuous evaluation and adaptation are essential to ensure the program's effectiveness and sustainability.

Prevalence of falls in the last weeks of life and relationship between falls, independence and quality of dying in Japan: a large prospective cohort study

ObjectiveThis study aims to determine the frequency of falls and their serious complications in palliative care units (PCUs), as well as explore the complex interplay between falls, independence and quality...