Poor Poor Performance Status Research Articles

Postoperative NEOadjuvant TEMozolomide followed by chemoradiotherapy vs. upfront chemoradiotherapy for Glioblastoma multiforme (NEOTEM) trial: interim results

Abstract Background Glioblastoma (GBM) is an aggressive brain tumor with poor survival rates despite current treatments. The standard of care (SOC) includes surgery, followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide (TMZ). This phase II trial assessed the safety and efficacy of neoadjuvant TMZ (nTMZ) before and during chemoradiotherapy in newly diagnosed GBM patients. Methods Newly diagnosed GBM patients who underwent maximal safe resection were randomized into two groups. One received nTMZ before standard chemoradiotherapy and adjuvant TMZ (intervention). The other received standard chemoradiotherapy followed by adjuvant TMZ (control). Primary endpoints were progression-free survival (PFS) at 6 and 12 months. Secondary endpoints included overall survival, radiological and clinical responses, and adverse events. Results Of 35 patients, 16 were in the intervention group and 19 in the control group. Median PFS was 3 months [95%CI:1.98-4.01] and 9 months [95%CI: 3.93-14.06] in the intervention and control group, with a high progression rate (73.4%) during nTMZ treatment. The 6-month PFS rates were 58% vs. 25% (P=0.042), and 12-month PFS rates were 26% vs. 25% (P=0.039) in the control and intervention groups. Patients with unmethylated MGMT, poor performance status (PS), or those undergoing biopsy or subtotal resection had worse PFS with nTMZ. Adverse events were similar between groups. Conclusions Neoadjuvant TMZ before SOC chemoradiotherapy did not improve outcomes for newly diagnosed GBM patients and is unsuitable for those with unmethylated MGMT or poor PS. It may benefit patients with near or gross total resection. Further research is needed to refine GBM treatment strategies.

Comparison of efficacy of gefitinib and osimertinib for untreated EGFR mutation-positive non-small-cell lung cancer in patients with poor performance status

BackgroundThere is a dearth of studies on the efficacy and safety of the tyrosine kinase inhibitors osimertinib (OSI) and gefitinib (GEF) in treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC), even in patients with poor performance status (PS). MethodsWe retrospectively reviewed and compared data of 113 patients with EGFR mutation-positive NSCLC with Eastern Cooperative Oncology Group PS 2–4 who were administered OSI 80 mg/day or GEF 250 mg/day from May 2016 to March 2022. ResultsThe GEF group (39 patients; median age: 74 years) included 20 patients with a PS of 2, 17 with a PS of 3, and 2 with a PS of 4. The OSI group (74 patients; median age: 76 years) included 48 patients with a PS of 2, 24 with a PS of 3, and 2 with a PS of 4. The overall response rates were 69% and 66% in the GEF and OSI groups, respectively. The disease control and PS improvement rates were 89% and 51% in both groups, respectively. The median progression-free survival in the GEF and OSI groups was 6.9 and 9.2 months, respectively (p = 0.15). The OSI group experienced better overall survival than the GEF group (median: 20.9 vs. 13.0 months, p = 0.0031). The incidence of pneumonitis was 10% and 11% in the GEF and OSI groups, respectively. One treatment-related death owing to pneumonitis occurred in the GEF group. ConclusionsOSI may be a useful treatment for untreated EGFR mutation-positive NSCLC with poor PS.

The Real-World Outcomes of Relapsed/Refractory Multiple Myeloma Treated with Elotuzumab, Pomalidomide, and Dexamethasone.

Introduction: A combination of elotuzumab, pomalidomide, and dexamethasone (EPd) was approved for the treatment of relapsed/refractory multiple myeloma (RRMM) following the ELOQUENT-3 phase II clinical trial. However, the clinical experience with this therapy is still limited. In this retrospective study, we analyzed the efficacy and safety of EPd in a real-world cohort of RRMM patients. Patients and Methods: The medical records of 22 patients who received EPd for RRMM at Yokohama Municipal Citizen's Hospital (Japan) between January 2020 and July 2021 were reviewed. Results: The median age of our cohort was 73.5 years. The overall response rate was 55%. With a median follow-up of 20.2 months, the median progression-free survival (PFS) was 9.1 months (95% confidence interval [CI], 2.5-23.0 months). The median PFS was shorter in patients with a poor performance status (PS) than in those with favorable PS (2.5 vs. 10.8 months; p < 0.01). Patients with prior daratumumab had significantly shorter PFS than those without prior daratumumab (2.1 vs. 23.0 months; p < 0.01). Additionally, patients with prior pomalidomide had significantly shorter PFS (1.7 vs. 10.3 months; p < 0.01). In the multivariate analysis, poor PS (hazard ratio [HR] = 4.1, 95% CI: 1.1-15.6; p = 0.04) and prior exposure to daratumumab (HR = 3.8, 95% CI: 1.1-13.8; p = 0.04) remained significantly associated with shorter PFS. Conclusions: The results of our study suggest that EPd is an active and well-tolerated regimen in RRMM, even in real-world patients. Furthermore, EPd may be useful, especially in daratumumab-naïve patients.

Survival prognostic factors in nonsmall cell lung cancer patients with simultaneous brain metastases and poor performance status at initial presentation

PurposeAlthough the treatment of nonsmall cell lung cancer (NSCLC) has rapidly progressed recently, there is little evidence of treatment for patients with symptomatic brain metastases (BM) and poor performance status (PS). However, in symptomatic BM patients, appropriate upfront intracranial treatment can often lead to rapid improvement in PS and effective systemic therapy. Thus, this study investigated the prognostic factors for the survival of poor PS NSCLC patients with synchronous BM. MethodsData of patients with BM and Karnofsky PS (KPS) ≤70 at the first diagnosis of NSCLC who were treated in our hospital between January 2017 and December 2021 were reviewed. Patient survival was compared among patients stratified by type of first-line regimen of systemic treatment. Correlations between patient characteristics and survival were examined. ResultsFifty patients receiving aggressive treatment were enrolled. The median survival times for tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and chemotherapy alone groups were 19 (95 % confidence interval [CI], 2.8–68.5), 19 (3.0–62.0), and 13 (1.2–24.8) months, respectively. Survival in the TKI and ICI groups was significantly longer than in the chemotherapy alone group (p = 0.046, TKI vs. chemo; p = 0.022, ICI vs. chemo; p = 0.023). Both sex and type of systemic treatment correlated to survival time on univariate analysis. Chemotherapy alone for systemic treatment [p = 0.034; hazard ratio (HR), 0.44 (0.20–0.94)] remained significant for predicting overall survival in the multivariate analysis. ConclusionEven in patients with poor PS and BM at the initial diagnosis of NSCLC, the ICI group had a survival time comparable to that of the TKI group when combined with tailor-made intracranial treatment. There is a subgroup in the patient population that was previously considered unsuitable for ICI, whose PS improves with individualized intracranial treatment, and who may benefit from immunotherapy.

Factors associated with cancer treatment resumption after ICU stay in patients with solid tumors

BackgroundPost-intensive care syndrome could be responsible for inability to receive proper cancer treatment after ICU stay in patients with solid tumors (ST). Our purpose was to determine the factors associated with cancer treatment resumption and the impact of cancer treatment on the outcome of patients with ST after ICU stay.MethodsWe conducted a retrospective study including all patients with ST admitted to the ICU between 2014 and 2019 in a French University-affiliated Hospital.ResultsA total of 219 patients were included. Median SAPS II at ICU admission was 44.0 [IQR 32.8, 66.3]. Among the 136 patients who survived the ICU stay, 81 (59.6%) received cancer treatment after ICU discharge. There was an important increase in patients with poor performance status (PS) of 3 or 4 after ICU stay (16.2% at admission vs. 44.5% of patients who survived), with significant PS decline following the ICU stay (median difference − 1.5, 95% confidence interval [-1.5-1.0], p < 0.001). The difference between the PS after and before ICU stay (delta PS) was independently associated with inability to receive cancer treatment (Odds ratio OR 0.34, 95%CI 0.18–0.56, p value < 0.001) and with 1-year mortality in patients who survived at ICU discharge (Hazard ratio HR 1.76, 95%CI 1.34–2.31, p value < 0.001). PS before ICU stay (OR 3.73, 95%IC 2.01–7.82, p value < 0.001) and length of stay (OR 1.23, 95%CI 1.06–1.49, p value 0.018) were independently associated with poor PS after ICU stay. Survival rates at ICU discharge, at 1 and 3 years were 62.3% (n = 136), 27.3% (n = 59) and 17.1% (n = 37), respectively. The median survival for patients who resumed cancer treatment after ICU stay was 771 days (95%CI 376–1058), compared to 29 days (95%CI 15–49) for those who did not resume treatment (p < 0.001).ConclusionDelta PS, before and after ICU stay, stands out as a critical determinant of cancer treatment resumption and survival after ICU stay. Multidisciplinary intervention to improve the general condition of these patients, in ICU and after ICU stay, may improve access to cancer treatment and long-term survival.

Induction chemotherapy backbone in frail patients with advanced NSCLC treated with chemotherapy plus pembrolizumab: a single institution retrospective audit of dose intensities from modified regimens.

Guidelines historically recommended mono-chemotherapy for the 1st line treatment of elderly patients with non-small cell lung cancer (NSCLC) and poor performance status (PS). Nowadays, there is no clear indication whether chemo-immunotherapy (chemo-IO) combinations can be effectively delivered in this population. We collected induction chemotherapy data in consecutive patients with advanced NSCLC treated with carboplatin-based chemotherapy regimens plus pembrolizumab, to compute the received dose intensity (RDI) from standard regimens or patient-tailored regimens modified due to age, comorbidities and PS. Comorbidities were stratified according to the comorbidity-polypharmacy score (CPS). The established cut-off of ≥85% for RDI was used to define adequate delivery. 116 pts were treated from Feb-20 to July-23, of whom 96 and 20 with non-squamous and squamous NSCLC, treated with carboplatin-pemetrexed or carboplatin-paclitaxel doublets plus pembrolizumab, respectively. The majority of patients were aged ≥ 70 years (52.6%), the median CPS was 5, with 58.6% having a CPS ≥5, whilst 47.4%, 44.8% and 7.8% had an Eastern Cooperative Oncology Group (ECOG) - PS of 0, 1 and 2, respectively. PD-L1 TPS were <1% in 31.9% and 1-49% in 65.4%. Overall, 47.4% received a priori modified regimens due to poor PS, age, or comorbidities. Among patients with non-squamous NSCLC, median received doses of carboplatin and pemetrexed were 1.37 AUC/week and 138.8 mg/m2/week, with RDIs of 86% and 75% (p < 0.01) for patients treated with standard or modified regimens, respectively. Of note, the RDI was 57.9% among patients with ECOG-PS 2. However, patients treated with modified regimens experienced similar toxicities as those treated with standard regimens, despite being older (p < 0.01), with higher PS (p < 0.01) and more comorbid (p = 0.03). Patients treated with modified regimens achieved a shorter survival (7.1 vs 13.9 months), which is comparable to IO-free historical controls. Among patients with squamous NSCLC, 90% received modified regimens upfront, with median received doses of carboplatin and paclitaxel of 1.19 AUC/week and 40 mg/m2/week, and an overall RDI of 73.5%. Although regimen modifications ensure a safe administration of chemotherapy plus pembrolizumab in frail patients, the RDI seems to be subtherapeutic, especially in those with squamous histology. Dedicated trials are needed to implement combination strategies in this population.

Enfortumab Vedotin for Elderly Advanced Urothelial Carcinoma Patients or Those With a Poor Performance Status.

The efficacy, safety, and liver toxicity of enfortumab vedotin (EV) for elderly advanced urothelial carcinoma (UC) patients and patients with a poor performance status (PS) are unclear. We retrospectively analyzed the efficacy, safety, and liver toxicity of EV in elderly patients and patients with a poor PS between December 2021 and August 2023. Sixty-two patients (≥75 years old, n=22; PS≥2, n=10) were enrolled. Patients with PS≥2 had significantly lower albumin levels than those with PS<2 (p=0.023). The objective response and disease control rates did not differ significantly between patients <75 and ≥75 years old (p=0.598 and p=0.769, respectively) or between those with PS<2 and PS≥2 (p>0.99 and p=0.178, respectively). Progression-free survival (PFS) and overall survival (OS) were not significantly different in patients <75 years and ≥75 years (p=0984, 0.368). A significant difference in PFS (p=0.047) but not OS (p=0.086) was observed between the PS<2 and PS≥2 groups. The rates of any-grade and severe (grade ≥3) adverse events did not differ significantly between patients <75 and ≥75 years (p=0.471, p=0.136) or between PS<2 and PS≥2 groups (p>0.99, 0.99). Aspartate aminotransferase (AST) levels significantly increased, but alanine aminotransferase levels did not, following EV treatment (p<0.001). Multivariate analyses revealed that the albumin level was an independent prognostic factor (hazard ratio=0.159; p<0.001). EV demonstrated similar efficacy and safety in elderly and younger patients with advanced UC. In patients with a poor PS, although the safety was similar, survival was significantly worse in terms of PFS, while the AST levels were significantly elevated.

Real-World Outcomes of Immunotherapy for Melanoma Brain Metastases in New Zealand.

Melanoma brain metastases (BMs) are associated with poor survival. Combination immune checkpoint inhibitors (ICIs) with anti-PD1 and anti-CTLA-4 are the international standard-of-care treatment. Most landmark clinical trials excluded real-world patients with symptomatic disease, poor performance status (PS), and steroid use. Despite the high incidence of melanoma in New Zealand (NZ), the only publicly funded systemic treatment is anti-PD1 monotherapy. The real-world outcomes for BMs after ICIs in NZ are unknown. Medical records of patients with melanoma BMs in seven cancer centers across NZ between September 1, 2016, and September 1, 2020, were evaluated. Clinicopathologic characteristics, treatment, intracranial (IC) tumor response rates, IC progression-free survival, and overall survival (OS) are reported. One hundred and forty-four patients received at least one dose of ICI. One hundred and thirty-three (93%) patients received anti-PD1 monotherapy. Almost a quarter of patients had poor baseline PS, 56% were symptomatic, and 33% had corticosteroids. Patients also received local therapies: 61 (42%) patients underwent surgery, 42 (29%) received whole brain radiation, and 47 (33%) received stereotactic radiation. The median OS was 15 months, and a third of patients were alive at 2 years. The toxicity of ICIs was at 28% and 15% for Common Terminology Criteria for Adverse Events grade 1-2 and 3-4 events, respectively. Of the patients who are still alive, 76% of patients remained symptomatic neurologically at last follow-up. Most patients in this NZ real-world study were symptomatic and received anti-PD1 monotherapy. Approximately one-third of treated patients are alive at 2 years, but most patients remained symptomatic. This highlights the need for more effective treatment and prospective management of their neurologic rehabilitation needs.

The performance status gap in immunotherapy for frail patients with advanced non-small cell lung cancer

PurposeIn advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown.MethodsPatients in the veterans affairs national precision oncology program from 1/2019–12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy.ResultsOf 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 − 0.88; Poor PS: OR 0.69, 95% CI 0.44 − 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 − 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 − 1.58).ConclusionFrail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.

Phase 3 randomized study for evaluation of physician choice Rx versus best supportive care as second-line or beyond therapy in head and neck cancer with poor performance status.

LBA6019 Background: Relapsed-recurrent head and neck squamous cell carcinoma (HNSCC) cancers have limited treatment options in the second line and beyond setting. Many of these patients have poor performance status (PS) and are subject to best supportive care (BSC). There is a lack of any level 1 evidence about the benefit of systemic therapy in HNSCC with poor PS. Methods: This was a randomized phase 3 superiority open-label multicentric study. Adult patients (age&gt;=18 years) with relapsed-recurrent HNSCC, qualified to receive 2nd line or beyond systemic palliative therapy and had ECOG PS 2-3 were eligible. Such patients underwent central stratified random assignment 2:1 to either physician choice therapy either triple metronomic chemotherapy (tablet erlotinib 150 mg [fixed-dose] OD, capsule celecoxib 200 mg [fixed-dose] BD, and oral weekly methotrexate 9 mg/m2 orally or intravenous docetaxel [75 mg/m2 3 weekly]) or BSC. The chemotherapy was continued either till the progression of the disease or till the development of intolerable side effects. The primary endpoint was 6 month-overall survival (OS). The OS in the 2 arms was estimated using the Kaplan-Meier method and by log-rank test. A p-value of 0.05 was considered significant. Sample size: The 6-month OS assumed based on our previous data was 20%, we had assumed that it would increase to 50% in the intervention arm with a type 1 error of 5%, type 2 error of 20%, 2:1 allocation (1- BSC and 2- intervention) and 10% lost to follow up rate. The sample size required was 66. The events required for analysis were 47. Results: The study recruited 66 patients between 1st September 2022 to 27th December 2022 with 44 patients in physician choice therapy (PCT) and 22 in the BSC arm. The data was censored for analysis on 1st March 2024. The median age was 50 years (Range 25-75) with a predominantly male population (n=53;85%). The ECOG PS was PS 2 in 56 (84.8%) and PS 3 in 10 (15.2%) patients. The predominant site of primary was the oral cavity with 52 patients (78.8%). The previous number of systemic lines of therapy received were 1 in 41 (62.1%), 2 in 22 (33.3%), and &gt;2 in 3 (4.5%) patients. Except for 2, all patients had a platinum refractory status (64;97%). The PCT was triple metronomic chemotherapy in 41 patients (93.2%; n=44) and docetaxel in 3 patients (6.8%; n=44). The 6-month OS was 9.09% (95% CI 1.56-25.1) in the BSC versus 53.8% (95% CI 37.9-67.2) in the PCT arm (P&lt;0.0001). The median overall survival in PCT was 223.0 days (95% CI 129-283) versus 77.5 days (95%CI 58 -110) in the BSC arm. The corresponding hazard ratio was 0.333 (95%CI 0.187-0.593; P&lt;0.0001). The data regarding adverse events will be presented at the conference. Conclusions: In this first-ever randomized study on poor PS HNSCC patients, warranting second-line and beyond therapy, the administration of systemic therapy led to a substantial improvement in OS. Clinical trial information: CTRI/2022/08/044733 .

Cisplatin-vinblastine-temozolomide regimen for patients with relapsed-refractory melanoma who are ineligible for clinical trials: A tertiary care center experience.

e21540 Background: Immune checkpoint inhibitors (IO) are at the forefront of treating patients with melanoma. Upon relapse, enrollment in clinical trials is encouraged. However, most trials in melanoma exclude those with prior IO-related grade 3/4 toxicities, active brain metastasis or poor performance status (PS). Lack of social support or insurance barriers are other issues preventing clinical trial enrollment. Cisplatin-Vinblastine-Temozolomide (CVT) was used extensively in the pre-IO era. Here, we report our experience with the CVT regimen in trial-ineligible patients with relapsed refractory melanoma (RRM). Methods: We conducted a retrospective review of patients with RRM who received CVT regimen. The regimen included Cisplatin (20mg/m2) + Vinblastine (1.5mg/m2) (both Day 1-3) + Temozolomide (125mg/m2) (Day 1-5) with peg-filgrastim support. All patients received at least 1 cycle of chemotherapy. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were recorded. Overall response rate (ORR) (CR+PR) at 3-months was the primary endpoint; and progression free survival (PFS), overall survival (OS), intracranial (IC) PFS, clinical benefit rate (CBR), ICRR, and toxicity at 3-months were secondary endpoints. Reason for trial ineligibility was also recorded. Results: Ten patients received CVT regimen for a median of 4 cycles (Interquartile range (IQR): 2-6). Five patients had cutaneous, 3 had acral and 2 had mucosal melanoma. Six were men, and 9 were white. Median follow up after starting CVT was 7.5 months (IQR: 2-14). At 3 months, 1 patient had CR, 4 had PR, and 2 had SD. ORR was 50% and overall CBR was 70% at 3-months. Median PFS was 5 months (IQR: 1-11). Four patients needed dose reduction due to myelosuppression. Two patients with PR discontinued CVT after 2 cycles (grade 3 fatigue). Upon progression, 8 patients with RRM had brain metastasis. Six patients got stereotactic radiation prior to starting CVT, and SD was recorded in these patients. The other 2 patients had CR in the brain metastasis with CVT (ICRR-25%). ICCBR was 100% at 3-months. The median ICPFS was 7 months (IQR (3-15). Three patients with acral melanoma were ineligible due to histology, 2 declined to participate (long commute, poor PS), 6 patients had prior grade 4 IO-related toxicity, and 2 patients were not supported by insurance. Two patients with PD (both acral melanoma) were later on enrolled in phase 1 clinical trial upon availability. Conclusions: In patients with RRM, CVT is an effective and well-tolerated regimen which can serve as a bridge till a trial becomes available. Our study also identifies potential barriers to enrollment on clinical trials where insurance issues and prior IO-related toxicity stand out as a major barrier. Real-world studies are needed to gain more insight into the potential barriers to trial enrollment.

Efficacy of Amamorelin in Advanced Pancreatic Cancer Patients with a Poor Performance Status.

Objective The efficacy of anamorelin in pancreatic cancer (PC) patients with a poor performance status (PS) is uncertain, as previous trials have excluded such patients. This study evaluated the efficacy of anamorelin in PC patients with a poor PS (2) compared with those with a good PS (0-1). Methods We retrospectively reviewed consecutive PC patients with cachexia who received anamorelin at our institution. The primary outcome was the proportion of responders, defined as those who maintained or gained body weight and appetite over 12 weeks. The secondary outcomes included anamorelin treatment duration, proportion of patients who discontinued anamorelin within 4 weeks (early discontinuation), and the overall survival. Results Forty-five patients (35/10) were included in this study. The proportion of responders was significantly lower in patients with a poor PS than in those with a good PS (0% vs. 37%, p=0.042). Moderate weight loss (5%-10%) and administration of pancreatic enzyme replacement therapy were associated with a response to anamorelin. A poor PS was significantly associated with a shorter treatment duration of anamorelin (14 vs. 93 days, p <0.001), a higher proportion of patients who discontinued anamorelin within 4 weeks (70% vs. 17%, p=0.003), and a reduced survival (62 vs. 188 days, p <0.001). A poor PS was associated with early discontinuation of anamorelin. Conclusions The efficacy of anamorelin is extremely limited in PC patients with a poor PS. Patients with PC with a poor PS may not be good candidates for anamorelin compared to those with a good PS.

Teclistamab Demonstrates Clinical Activity in Real-World Patients Ineligible for the Pivotal Majestec-1 Trial

Introduction Treatment options for relapsed/refractory multiple myeloma (RRMM) are limited and associated with a poor median overall survival (OS) of 12.4 months (m) (Mateos et al. Leukemia 2022). The MajesTEC-1 trial demonstrated promising clinical activity of teclistamab (Tec), a BCMAxCD3 bispecific antibody, with an overall response rate (ORR) of 63%, complete response rate (CR) of 39.4%, median progression-free survival (PFS) of 11.3 m, and OS of 18.3 m. Here we present the results of a multicenter, retrospective study examining real-world patient characteristics and outcomes in patients with RRMM receiving Tec outside of a clinical trial, including those who would have been ineligible for the registrational study. Methods An IRB-approved retrospective study of patients with RRMM treated with Tec at 4 academic centers was performed. Patient demographics, prior treatments, clinical outcomes and toxicities with special attention to cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infection were extracted from the electronic patient record. Response rate was compared using Fisher's exact test. Median PFS and OS were estimated by Kaplan-Meier and compared using the log-rank test. Trial eligibility was evaluated using the MajesTEC-1 eligibility criteria. Results A total of 45 patients, who received at least 1 dose of Tec, were evaluated. Of these 39% were derived from under-represented minorities (25% Black, 14% Hispanic). Patient characteristics and comparison to the MajesTEC-1 population are summarized, Table 1. High-risk cytogenetic features were present in 42.2% of patients, and 46.7% had extra-medullary disease (EMD). All patients were triple class exposed and 80% were penta-class exposed. Most patients (84.4%) would have been ineligible for MajesTEC-1 due to cytopenias (44.4%), prior BCMA-directed therapy (42.2%), inadequate washout (42.2%), and poor performance status (PS) (26.7%). Therapy was delivered according to protocol with no increased rate of infections or bleeding, even in the group of patients with low blood counts and poor PS. CRS/ICANS events of any grade were observed in 55% and 13% of patients, respectively, during step-up dosing. Most CRS/ICANS events were mild-moderate in severity (CRS 42.2% grade 1, 11.1% grade 2; ICANS 4.4% grade 1, 0% grade 2) and were managed conservatively with antipyretics, tocilizumab (37.8%), and steroids (13.3%). Grade 4 CRS and ICANS were only seen in 1 patient; a separate individual experienced grade 5 ICANS after the third step up dose. The overall response rate (ORR) was 48.9% (95% CI 33.7-64.2) with 22.2% (95% CI 11.2-37.1) achieving at least a very-good partial response (VGPR). On univariate analysis prior anti-BCMA exposure was associated with an adverse ORR (23% vs 61%; p=0.02). Ineligibility for enrollment in MajesTEC-1, the presence of high-risk cytogenetics or EMD were not associated with ORR or depth of response. Updated follow up time, median PFS and OS will be presented at the meeting to allow time for data to mature. The presence of high-risk cytogenetics was associated with worse PFS (median NR vs 2.1 m, HR 2.32; p=0.041). Receipt of prior BCMA therapy and MajesTEC-1 ineligibility were not associated with PFS or OS. At the time of data cut-off, 19 (42.2%) patients remained on Tec; reasons for discontinuation included disease progression, infections, and CRS/ICANS in 19 (42.2%), 4 (8.8%), and 3 (6.7%) patients, respectively. Conclusion Overall, Tec demonstrated significant clinical activity even in a group of heavily pre-treated real-world patients comprising high-risk and extramedullary disease populations. The overall toxicity profile was similar to prior reports demonstrating that side effects can be readily managed using simple approaches with only limited patients needing more intensive interventions. These results also suggest Tec may be used in patients previously excluded from clinical trials because of adverse clinical characteristics with high ORR being seen and an absence of increased toxicity. In the BCMA-naive population ORR were similar to MajesTEC-1, but were lower in the previously BCMA-exposed population. High-risk cytogenetics and EMD remain adverse prognostic features with Tec despite similar ORR.

Prognostic effect of cachexia in patients with non‐small cell lung cancer receiving immune checkpoint inhibitors

The presence of cachexia in cancer patients negatively affects the quality of life and survival. However, the impact of cachexia on immunotherapy, such as PD-1/L1 inhibitors, is not fully understood. Therefore, we examined whether cancer cachexia affects the prognosis of patients with non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. We retrospectively screened patients with pathologically confirmed advanced or recurrent NSCLC who were treated with PD-1/PD-L1 monotherapy at Kurume University Hospital. We defined cancer cachexia as weight loss of at least 5% during the past 6 months or any degree of weight loss more than 2% and BMI <20. Among 182 patients, 74 had cancer cachexia. The presence of cachexia was significantly associated with females, poor performance status (PS), never-smokers, and driver mutations. Multivariate analysis revealed that poor PS and being a smoker were associated with the presence of cachexia. Patients with cancer cachexia had significantly shorter progression-free survival (PFS) and overall survival (OS). In the multivariate analysis, PS and sex were significantly correlated with PFS, whereas PS and cachexia were significantly correlated with OS. Subanalysis revealed that patients in the PS0/without cachexia group had longer PFS and OS than those in the cachexia or PS1-3 group. In NSCLC patients, cachexia was associated with a worse prognosis, irrespective of tumor PD-L1 expression, indicating that cachexia is a predictive factor for NSCLC patients receiving immune checkpoint inhibitors.

Sequencing impact and prognostic factors in metastatic castration-resistant prostate cancer patients treated with cabazitaxel: A systematic review and meta-analysis.

Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify prognostic factors of oncologic outcomes in mCRPC patients treated with cabazitaxel. PUBMED, Web of Science, and Scopus databases were searched for articles published before January 2022 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they investigated pretreatment clinical or hematological prognostic factors of overall survival (OS) in mCRPC patients with progression after docetaxel treated with available treatments including cabazitaxel. Overall, 22 studies were eligible for the meta-analysis. In mCRPC patients treated with docetaxel, subsequent treatment with cabazitaxel was associated with better OS compared to that without cabazitaxel (pooled hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.56-0.89). Among the patients treated with cabazitaxel, several pretreatment clinical features and hematologic biomarkers were associated with worse OS as follows: poor performance status (PS) (pooled HR: 1.92, 95% CI: 1.33-2.77), presence of visceral metastasis (pooled HR: 2.13, 95% CI: 1.62-2.81), symptomatic disease (pooled HR: 1.47, 95% CI: 1.25-1.73), high PSA (pooled HR: 1.76, 95% CI: 1.27-2.44), high alkaline phosphatase (ALP) (pooled HR: 1.45, 95% CI: 1.28-1.65), high lactate dehydrogenase (LDH) (pooled HR: 1.54, 95% CI: 1.00-2.38), high c-reactive protein (CRP) (pooled HR: 4.40, 95% CI: 1.52-12.72), low albumin (pooled HR:1.09, 95% CI: 1.05-1.12) and low hemoglobin (pooled HR:1.55, 95% CI: 1.20-1.99). Sequential therapy with cabazitaxel significantly improves OS in post-docetaxel mCRPC patients. In mCRPC patients treated with cabazitaxel, patients with poor PS, visceral metastasis, and symptomatic disease were associated with worse OS. Further, pretreatment high PSA, ALP, LDH or CRP as well as low hemoglobin or albumin, were blood-based prognostic factors for OS. These findings might help guide the clinical decision-making for the use of cabazitaxel and prognostication of its OS benefit.

Exceptional responses to PARP inhibitors in patients with metastatic breast cancer in oncologic crisis.

Cancers deficient in homologous recombination DNA repair, such as those with BRCA1 or BRCA2 (BRCA1/2) mutations rely on a pathway mediated by the enzyme poly(adenosine diphosphate-ribose) polymerase (PARP). PARP inhibitors (PARPi's) have demonstrated efficacy in treating patients with germline (g)BRCA1/2, somatic (s)BRCA1/2, and gPALB2 mutations in clinical trials. However, patients with a poor performance status (PS) and those with severe organ impairment are often excluded from clinical trials and cancer-directed treatment. We report the cases of two patientswith metastatic breast cancer who had poor PS, significant visceral disease, and gPALB2 and sBRCA mutations, who derived significant clinical benefit from treatment with PARP inhibition. Patient A had germline testing demonstrating a heterozygous PALB2 pathogenic mutation (c.3323delA) and a BRCA2 variant of unknown significance (c.9353T>C), and tumor sequencing revealed PALB2 (c.228_229del and c.3323del) and ESR1 (c.1610A>C) mutations. Patient B was negative for pathologic BRCA mutations upon germline testing, but tumor sequencing demonstrated somatic BRCA2 copy number loss and a PIK3CA mutation (c.1633G>A). Treatment with PARPi's in these two patients with an initial PS of 3-4 and significant visceral disease resulted in prolonged clinical benefit. Patients with a poor PS, such as those described here, may still have meaningful clinical responses to cancer treatments targeting oncogenic drivers. More studies evaluating PARPi's beyond gBRCA1/2 mutations and in sub-optimal PS would help identify patients who may benefit from these therapies.

Clinical characteristics and outcomes of trial-ineligible patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving androgen receptor targeted (ART) therapy.

118 Background: mCRPC pts with significant comorbidities or poor performance status (PS) are often excluded from clinical trials for ART. These cohorts may not be representative of or comparable to real-world pts. We aimed to determine whether (1) baseline characteristics or (2) survival outcomes differed in pts with mCRPC categorized as eligible or ineligible for ART clinical trials. Methods: We screened for pts with mCRPC treated with abiraterone (abi-) or enzalutamide (enza-) at our institution between 2010 and 2021. Baseline characteristics were reviewed at treatment start and ART course recorded. We applied the inclusion/exclusion criteria from clinical trials, COU-AA-301, COU-AA-302, PREVAIL, and AFFIRM, to categorize pts as ineligible or eligible. Fischer’s exact was used to evaluate pt characteristics. Cox proportional hazards model was used to compare survival outcomes. Results: We identified 150 pts with mCRPC who initiated abi- or enza-. 54.7% of pts were deemed trial ineligible. Among pts on abi-, 48 of 86 (55.8%) pts were ineligible. Among those on enza-, 34 of 64 (53.1%) were ineligible. Common reasons for ineligibility included poor PS, radiation during treatment, and trial specific comorbidities. Among ineligible pts, 11% were post-chemotherapy compared to 20.6% of eligible pts (p = .162). Notably, trial ineligible pts were more likely to be non-Hispanic black when compared to trial eligible pts (29.3% vs. 17.6%, p = 0.036). Median OS was 30.2 for ineligible pts and 37.1 for eligible pts p = 0.46). for the ineligible pts and eligible pts respectively and there was no significant difference on univariate or multivariate analyses (HR: 0.84 [0.54, 1.32;]. Conclusions: Pts classified as trial ineligible had comparable survival outcomes when compared to trial eligible pts. Consistent with prior research on systemic racism in clinical trials, ineligible pts were more likely to identify as Black compared to eligible pts. Further research is warranted to confirm safety of ART in ineligible pts and identify strategies for reducing racial disparity gaps in cancer clinical trials.

267: PERFORMANCE STATUS AS A PREDICTOR OF ICU MORTALITY IN CRITICALLY ILL CANCER PATIENTS

Introduction: Frailty and poor performance status (PS) have been associated with low survival in the general intensive care units (ICUs). However, there is limited data focused on critically ill cancer patients. As demand for ICU admission among the cancer population rises, there is a need to prioritize access, especially in resource-limited settings. Therefore, we assessed the association between baseline PS to ICU mortality in critically ill cancer patients. Methods: A retrospective cohort of adult critically ill cancer patients admitted between 12/2020 and 07/2021 to an oncological hospital in Guayaquil, Ecuador. PS deterioration was measured with the Eastern Cooperative Oncology Group scale (ECOG) prior to hospital admission, and it was classified into mild (ECOG 0-1), moderate (ECOG 2), and poor (ECOG 3-4). We conducted a logistic regression to establish associations between characteristics and ICU mortality. Results: A total of 200 patients were included, with a mean age of 57.9 years (SD 16). Of them, there were 168 (84%) patients with solid tumors and 32 (16%) with hematological malignancies. Most patients were post-surgical (52%) and the rest were medical (48%). Regarding PS deterioration, we found 71 (35.5%) with mild PS, 95 (47.5%) with a moderate PS and 34 (17.0%) with a poor PS. Most patients in the poor PS group (70.6%) had a solid tumor. Overall, 96 (48%) patients required invasive mechanical ventilation (IMV) and 88 (44%) vasopressors. Patients with poor PS required more days on IMV (1.5 vs 1 vs 0; p=.001) and days on vasopressors (1vs 1 vs 0; p=.019) than the moderate and mild groups, respectively. The overall ICU mortality was 29%. Poor PS had higher risk of ICU mortality ratio (OR 5.013 [95% CI: 1.6–15.9]) than SOFA (OR 1.3 [95% CI: 1.1-1.6], APACHE II (OR 1.1 [95% CI: 1-1.2], and m-NUTRIC (OR 0.99 [95% CI: 0.7-1.3] scores. Conclusions: A poor performance status was associated with a 5-fold increased risk of ICU mortality. Additionally, poor PS implied a higher requirement of life-sustaining therapies like IMV and vasopressors. The association between ECOG and mortality was superior to the classic ICU scores such as, APACHE II, SOFA and m-NUTRIC. Future research should determine if the PS could be a triage tool in settings with low ICU capacity.

Audit of screen failure in 15 randomised studies from a low and middle-income country.

Growth and development in patient management occurs via randomised studies. Screen failure is a significant hurdle while conducting randomised studies. There is limited data available from low and middle-income countries about factors resulting in screen failure. Hence, this audit was performed to identify the proportion of patients who screen failed and to elucidate reasons for the same. This was an audit of 15 randomised studies performed by medical oncology solid tumour unit II of Tata Memorial Centre. The screening logs of these studies were acquired. From the screening logs, data regarding the number of patients who had screen failed & reason for the same were obtained. Descriptive statistics were performed. A total of 7,481 patients were screened for 15 randomised clinical studies. Out of these, 3,666 (49.0%) patients were enrolled into trials and 3,815 (51.0%) screen failed. The most common reason for screen failure was 'not meeting inclusion criteria' (54.9%) followed by declining to take treatment (22.2%). Other factors that affect enrolment were 'not willing to stay in the locality of the trial site' (6.2%), being recruited in other studies (3.7%), poor performance status (PS) (3.4%), non-compliance (2.2%), meeting exclusion criteria (0.9%) and 'other' (6.5%). The commonest causes of screen failure in lower and middle-income countries are non-meeting of inclusion criteria followed by declining to take treatment, not willing to stay in locality of trial site, recruited into other studies, poor PS, non-compliance, meeting exclusion criteria & 'other'. This information would help analysing and hence planning of newer strategies to decrease the rate of screen failure.

A phase II study of carboplatin and etoposide plus durvalumab for previously untreated extensive-stage small-cell lung cancer (ES-SCLC) patients with a poor performance status (PS): NEJ045A study protocol

BackgroundSmall-cell lung cancer (SCLC) accounts for 12–15% of lung cancers and has a limited prognosis, with approximately one-third of SCLC patients having a poor performance status (PS). Patients with extensive-stage (ES) SCLC and a poor PS have a poor prognosis. For this population, overall survival from carboplatin and etoposide treatment is 7–8 months, and treatment development is an unmet medical need. Recently, the combination of an anti-PD-L1 (a ligand for programmed cell death 1) antibody and platinum-based chemotherapy has become the standard of care for ES-SCLC patients with a good PS (PS 0–1). We hypothesized that the combination of the anti-PD-L1 antibody durvalumab with carboplatin and etoposide would be feasible and effective for such patients.MethodsWe initiated a multicenter phase II study of durvalumab combined with carboplatin and etoposide in previously untreated ES-SCLC patients with a poor PS (PS 2–3). Eligible patients will receive durvalumab plus carboplatin and etoposide every 3 to 4 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. The dosages of carboplatin and etoposide for the second and subsequent cycles will be adaptively determined based on the adverse events of the first cycle. A total of 56 patients (43 patients with a PS of 2 and 13 patients with a PS of 3) will be enrolled in this study, with a 24-month enrollment period and a 12-month follow-up. The primary endpoint is the tolerability of carboplatin and etoposide plus durvalumab in previously untreated ES-SCLC patients with a poor PS. The secondary endpoints are the 1-year survival rate, objective response rate, progression-free survival, overall survival, ratio of PS improvement, and safety.DiscussionThe results of this study are intended to establish the safety and efficacy of carboplatin and etoposide plus durvalumab in patients with ES-SCLC and a poor PS.Trial registrationJapan Registry of Clinical Trials (jRCT), jRCTs031200319. Registered 21 January 2021, https://jrct.niph.go.jp/en-latest-detail/jRCTs031200319