Poor Performance Status Patients Research Articles

Pembrolizumab in Patients with Advanced Urothelial Carcinoma with ECOG Performance Status 2: A Real-World Study from the ARON-2 Project.

The benefit of immune checkpoint inhibitors (ICIs) for poor performance status patients with advanced urothelial carcinoma (UC) remains unknown. In the present sub-analysis of the ARON-2 study, we investigated the role of pembrolizumab for advanced UC patients with ECOG (Eastern Cooperative Oncology Group) performance status (ECOG-PS) 2. Patients aged ≥18 years with a cytologically and/or histologically confirmed diagnosis of advanced UC progressing or recurring after platinum-based therapy and treated with pembrolizumab between 1 January 2016 to 1 April 2024 were included. In this sub-analysis we focused on patients with ECOG-PS 2. We included 1,040 patients from the ARON-2 dataset; of these, 167 patients (16%) presented an ECOG-PS 2. The median overall survival (OS) was 14.8 months (95% confidence interval (CI) 12.5-16.1) in the overall study population, 18.2 months (95% CI 15.8-22.2) in patients with ECOG-PS 0-1, and 3.7 months (95% CI 3.2-5.2) in subjects with ECOG-PS 2 (p<0.001). The median progression-free survival (PFS) in the overall study population was 5.3 months (95% CI 4.3-97.1), 6.2 months (95% CI 5.5-97.1) in patients with ECOG-PS 0-1, and 2.8 months (95% CI 2.1-3.4) in patients with ECOG-PS 2. Among the latter, liver metastases and progressive disease during first-line therapy were significant predictors of OS at both univariate and multivariate analyses. For PFS, univariate and multivariate analyses showed a prognostic role for lung metastases, liver metastases, and progressive disease during first-line therapy. This large real-world evidence study suggests the effectiveness of second-line pembrolizumab for mUC patients with poor performance status. The presence of liver metastases and progressive disease during first-line therapy is associated with worse clinical outcomes and, thus, should be taken into account when making treatment decisions in clinical practice.

High early mortality after percutaneous liver biopsy in metastatic cancer: national analysis

ObjectiveThe study aimed to assess outcomes in patients undergoing liver biopsy for metastatic cancer, focusing on mortality rates and chemotherapy following their biopsy.MethodsHospital Episode Statistics data from 2010 to 2019...

Real-world efficacy and toxicity of ipilimumab and nivolumab as first line treatment of metastatic renal cell carcinoma (mRCC) in a subpopulation of elderly and poor performance status patients.

367 Background: Ipilimumab and nivolumab (ipi/nivo) improved overall survival (OS) and response rates compared to sunitinib in the pivotal Checkmate 214 trial of intermediate/poor risk mRCC. A subgroup analysis showed no significant difference in OS for ipi/nivo in pts 65 to 75 years old (yo), as well as pts &gt;75 yo. In another subgroup analysis, Karnofsky performance status (KPS) &lt;70 was associated with worse median OS compared with pts with KPS ≥ 70. We evaluated efficacy and toxicity of ipi/nivo in an older and frailer population in a real-world cohort. Methods: Analysis was conducted on a real-world cohort with mRCC (N=378) treated with ipi/nivo as first line treatment from the Canadian Kidney Cancer Information System (CKCis) database from January 2011 to March 2022. Median follow-up was 14.3 m (range 0 to 87.6). A comparison was made between outcomes and toxicity in pts ≥ versus (vs) &lt;70 yo, ≥ vs &lt;75 yo, KPS &lt; vs ≥70, and ≥70 yo with KPS &lt;70 vs &lt;70 yo with KPS &gt;70. Toxicity was graded as per CTCAE v4.03 or any toxicity that resulted in a dose/schedule change. OS, progression free survival (PFS) and time to treatment failure (TTF) were calculated by Kaplan-Meier analysis. Log rank tests were used for comparison between groups. Multivariate analysis was done including IMDC for all outcomes. Results: Median OS was worse in older patients at 30.0 m in pts ≥ 70 yo vs 45.4 m in pts &lt; 70 yo (p=0.060), and 19.0 m in the pts ≥ 75 yo vs 45.5 m in pts &lt; 75 yo (p=0.003) despite similar disease control rates and toxicity. Median PFS was similar in younger and older pts: &lt; vs ≥ 70 yo (p=0.560) and &lt; vs ≥ 75 yo (p=0.296). Median TTF was comparable in &lt; 70 yo and ≥ 70 yo (p=0.106) and &lt; 75 and ≥ 75 yo groups (p-value=0.733). Median OS, PFS and TTF were comparable in pts KPS &lt; 70 vs pts KPS ≥ 70 and in pts ≥70 yo with KPS &lt; 70 vs pts &lt; 70 yo with KPS &gt;70. Adjusted and unadjusted analysis showed no difference in OS and PFS between groups. Conclusions: Use of ipi/nivo in mRCC in older patients was associated with inferior OS, while decreased performance status had equivalent OS. Both groups had equivalent TTF and PD without higher toxicity. We believe that ipi/nivo is a reasonable treatment option for older and low performance status patients. [Table: see text]

HIDDEN2: Study protocol for the hospital deep vein thrombosis detection study in patients with cancer receiving palliative care

IntroductionMedical patients, admitted acutely to hospital, are at risk of venous thromboembolism (VTE). Clinical guidelines advise thromboprophylaxis prophylaxis for those at high risk of VTE. VTE is a common sequela...

Effects of Palliative Chemotherapy in Unresectable or Metastatic Colorectal Cancer Patients With Poor Performance Status

IntroductionColorectal cancer is the second most common cancer in both genders and often presents as a metastatic, unresectable, or recurrent disease in early follow-up. It is uncertain the benefit of oxaliplatin-based palliative chemotherapy (CT) in the first line of treatment in patients with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) 3 and 4. These patients are systematically excluded from clinical trials but may be treated in clinical practice. MethodsWe conducted a prospective observational cohort whose primary outcome was improving at least 2 points in the worst symptom in the Edmonton Symptom Assessment System Scale (ESAS-r), without grade 3 to 4 toxicity, comparing baseline and fourth week of treatment. Secondary endpoints included quality of life using the European Quality of Life-5 dimensions questionnaire, toxicity, response rate, clinical improvement of ECOG PS, and overall survival (OS). ResultsWe included 28 patients, and 12 (42.8%) achieved the primary endpoint. Median overall survival was 86 days, 46% of patients did not respond to the fourth-week reevaluation due to clinical deterioration, and 17.8% presented toxicity grade ≥3, with 5 patients dying from toxicity. In addition, ECOG PS 4 or cholestasis had poorer overall survival. Finally, 25% and 53.6% of patients received these treatments in the last 14 and 30 days of life, respectively. ConclusionIn the present study, palliative multiagent chemotherapy in poor performance status patients with non-molecularly selected colorectal cancer tended to impact tumor symptoms control; however, there is no benefit in OS and a considerable risk of toxicity and treatment-related death.

Real-world outcomes of pembrolizumab for platinum-refractory advanced urothelial carcinoma: Efficacy, safety, and evidence for trial-unfit patients.

Pembrolizumab, monoclonal antibody targeting programmed cell death 1, is widely used for platinum-refractory urothelial carcinoma (UC) patients. Although the survival benefit of pembrolizumab was proven in the well-designed phase III trial, these data represent only a part of patients due to strictly defined eligibility criteria. The patients' characteristics in the clinical practice are much more heterogenous than those of trial participants. The real-world experience is useful to validate the trial result and find suitable candidates for the treatment. Similarly, real-world data plays a significant role in addressing the efficacy and safety of special populations, such as poor performance status or older patients. This review summarizes the real-world evidence on pembrolizumab for platinum-refractory UCs and discusses the clinical risk factors and efficacy for trial-ineligible patients.

Four-Phase, Definitive Chemoradiation for a Real-World (Poor Risk and/or Elderly) Patient Population With Locally Advanced Non-small Cell Lung Cancer.

IntroductionWith the incorporation of modernized radiotherapy, chemotherapy, and immunotherapy, treatment outcomes have improved for patients with locally advanced, unresectable diseases. Elderly or poor performance status patients comprise more than half of non-small cell lung cancer (NSCLC) patients, but they are often underrepresented or excluded in clinical trials. Split-course concurrent chemoradiotherapy can be an effective treatment, showing good adherence and a favorable toxicity profile for unresectable, locally advanced NSCLC.MethodWe identified locally advanced NSCLC cancer patients via a single institution retrospective study. Patients were treated using a four-phase, split-course external beam radiotherapy approach with concurrent chemotherapy. The primary endpoints analyzed were completion rate, incidence, and severity of treatment-related toxicities, progression-free survival (PFS), and median overall survival (OS).ResultsThirty-nine locally advanced lung cancer patients were treated with split-course chemoradiation (CRT). The median age at diagnosis was 73 years old. Seventeen patients had an Eastern Cooperative Oncology Group (ECOG) performance score of 2. Twenty-three patients had a clinical diagnosis of chronic obstructive pulmonary disease (COPD), and 10 patients were on home oxygen at the time of diagnosis. All patients completed 6000 centigrays (cGy) of radiation, and 95% of the patients completed at least three cycles of concurrent chemotherapy. No patients experienced grade 3 to 5 acute thoracic toxicities. Overall median survival was 12.7 months, and PFS was 7.5 months.ConclusionOur retrospective analysis of 39 poor risk and/or elderly patients with locoregional NSCLC treated with concurrent CRT via a split-course regimen suggests favorable oncologic outcomes and superb treatment completion rates and toleration.

LITTing up Gliomas—Is the Future Bright?

BackgroundLaser interstitial thermal therapy (LITT) represents an attractive therapeutic strategy for several intracranial pathologies; however, there is a paucity of literature regarding its efficacy for the treatment of gliomas.MethodsMEDLINE, EMBASE, Scopus, and Web of Science were searched from inception until March 19, 2021. Studies specifically relating to the use of LITT in treatment of glioma were eligible for inclusion. A meta-analysis of means was performed to assess the progression-free survival (PFS) and overall survival (OS) following LITT and descriptive statistics relating to patients undergoing LITT were collated and a meta-analysis of proportions was also performed to assess the rate of complications.ResultsIn total, 17 studies were included for the meta-analysis, comprising 401 patients with 408 gliomas of which 88 of 306 (28.8%) were grade 1 or 2 and 218 of 306 (71.2%) were grade 3 or 4. Of these, 256 of 408 (62.8%) were primary presentation and 152 of 408 (37.2%) were recurrent. The pooled mean OS was 13.58 months (95% confidence interval [CI] 9.77–17.39) and the PFS was 4.96 months (95% CI 4.19–5.72). The OS and PFS of recurrent glioblastoma were 12.4 months (95% CI 9.61–16.18) and 4.84 months (95% CI 0.23–9.45), respectively. Complications occurred in 114 of 411 (24%; 95% CI 14–41), of which 44 (11%) were transient deficits.ConclusionsThere is an increasing body of evidence demonstrating the use of LITT in the surgical management of deep-seated gliomas in patients of poor performance status. However, further studies are required to interrogate the clinical effectiveness of LITT in the setting of gliomas as well as assessing the survival benefit versus standard treatment alone.

ALK-positive advanced non-small cell lung cancer patients with poor performance status: Outcomes in a real-world scenario.

BackgroundAnaplastic lymphoma kinase (ALK) inhibitors have shown significant efficacy in ALK -rearranged non-small cell lung cancer (NSCLC) patients with good performance status (PS) in multiple randomised studies. However, there is limited data on patients with poor performance status.Patients and methodsWe carried out a retrospective analysis of prospectively collected data of patients with ALK-rearranged NSCLC and Eastern Cooperative Oncology Group (ECOG) PS of 2–4 treated at a single academic cancer centre from January 2013 to November 2018. The outcomes, progression-free survival (PFS) and overall survival (OS) were calculated from the date of diagnosis. SPSS version 20 was used for all statistical calculations.ResultsOut of the total 441 ALK-positive patients, 97 (21.9%) had ECOG PS 2–4 (poor PS). The median PFS was 9.3 months (95% CI = 6.6–12.0) as compared to 14.9 months (95% CI = 13.4–16.4) for patients with a PS of 0–1 (HR = 1.38, 95% CI = 1.04–1.84, p = 0.027). The corresponding median OS were 17.9 months (95% CI = 12.8–23.1) and 33.5 months (95% CI = 28.6–38.4), respectively (HR = 1.89, 95% CI = 1.36–2.62, p < 0.001). Among poor PS patients, a subgroup of patients with PS 2 had median OS of 20.6 months (95% CI = 10.8–47.3) as compared to 8.6 months for PS 3–4 (95% CI = 7.8–27.8) (HR = 1.79, 95% CI = 1.01–3.20, p = 0.047). The patients treated with upfront ALK inhibitors had better survival as opposed to those treated with chemotherapy. On multivariate analysis, PS 3–4, smoking, stage 4 and not using ALK inhibitors as first-line therapy were associated significantly with poor outcomes.ConclusionThe ALK-rearranged NSCLC patients with poor PS derived significant benefits with ALK inhibitors. The outcomes were significantly poorer as compared to patients with PS 0–1; the subgroup of patients with PS 2 had better outcomes as compared to patients with PS 3–4.

Definitive chemoradiotherapy +/- induction chemotherapy in esophageal cancer: A real-world experience.

e16072 Background: The SEER 5-year overall survival rate for all stages of esophageal cancer (EC) was 25% in 2019. Definitive chemoradiation (CRT) remains the primary treatment approach for locally advanced EC in the US, however, there are data to support use of induction chemotherapy (CT) in addition to CRT, particularly in adenocarcinoma (AC) histology. The purpose of our study was to assess outcomes in EC patients treated with definitive CRT (+/- induction) to determine which prognostic factors predicted for better survival in a recent, real-world cohort of patients, including those with limited stage IV disease. Methods: This retrospective study included Stages II-IVB (AJCC 8th ed.) EC patients treated with definitive CRT (radiation dose of ≥40 Gy and at least two cycles of concurrent CT [+/- induction CT, +/- esophagectomy]) at our institution between 2008 and 2020. To analyze prognostic factors and estimate OS, univariate models (UVA) and a multivariate (MVA) Cox proportional hazards regression model including age, Stage (II, III, IVA, IVB), AC vs. SCC, esophagectomy, ECOG performance status (PS), and induction CT were performed. Results: Of the 183 patients treated with definitive CRT, 18 were stage II, 119 stage III, 21 stage IVA, and 25 stage IVB. There were 45 SCC and 138 AC patients (Table). Prognostic factors associated with prolonged OS on MVA included lower PS (p&lt;0.01) and esophagectomy (p = 0.05). Stage IVA was associated with shorter survival (p&lt;0.01). Induction CT (delivered in 53% of AC, 31% SCC) was associated with improved survival on UVA (p=0.04), but not MVA (p = 0.08). By histology, 5-year survival rate was 42.7% and 18.2% for AC and SCC, respectively. Conclusions: At our institution, those who received an esophagectomy and those with lower ECOG scores had better survival. The 5-year survival rate was higher for AC patients compared to SCC, with more AC patients receiving esophagectomy and induction CT (significant on UVA, but not MVA). The 5-year survival rate for AC in our study was nearly identical to that seen in the CROSS trial (Shapiro et al. 2015) AC cohort but included &gt;25% stage IV patients. This modern cohort also included poor PS (ECOG≥2) patients (9.2% AC and 13.6% SCC), suggesting induction CT, in addition to pre-operative CRT + surgery, may have added benefit in a real-world practice. Thus, further prospective study is needed.[Table: see text]

PD-9 Three-arm phase II/III randomized controlled trial in patients with unresectable/metastatic gall bladder cancer with poor performance status: Erlotinib or capecitabine v/s best supportive care

Currently there is no standard of care for Eastern Cooperative Oncology Group (ECOG) poor performance status (PS) patients (PS-III) with unresectable/metastatic Gall Bladder Cancer (GBC). Being unfit for chemotherapy, these patients receive only best supportive care (BSC) resulting in a very dismal outcome. A report published from M.D. Anderson Cancer Centre stated median overall survival (OS) of only one month in patients with poor PS with GBC. This single centre, prospective randomized controlled phase II/III, open label trial was done at a tertiary health care centre in India. Patients (above 18 years) with histologically confirmed unresectable/ metastatic GBC with adequate organ function and ECOG PS-III were included. Patients with prior adjuvant chemotherapy/erlotinib/capecitabine in last 6 months, active malignancy other than GBC, lactating and pregnant women, and HIV-positive status were excluded. Random allocation (1:1:1) was done to one of the three arms - Erlotinib (150 mg OD) + BSC, Capecitabine + BSC or BSC alone using computer-generated sequence. The primary end point was median OS, defined as time from randomisation to death, in the intention-to-treat population. A sample size of 105 was estimated, assuming median OS in BSC, Erlotinib+BSC and Capecitabine+BSC as 2, 4 and 5 months respectively (taking two-sided alpha error as 0.05 and power as 80%). Between Dec 27, 2017 and January 18, 2021, 201 patients were screened, of which 105 were randomized to Erlotinib +BSC (n = 36), Capecitabine +BSC (n = 36) or BSC alone arm (n = 33). After a median follow up of 10 months (IQR 3.9- 11.5), there were 82 deaths in the whole cohort. The median OS in Erlotinib arm was significantly higher at 3.84 months (2.33- 4.67) compared to 1.77 months (1.18- 2.73) in BSC only arm, with hazard ratio (HR) of 0.50 (95% CI - 0.26 -0.95), p = 0.02. However, there was no statistically significant difference observed in survival between Capecitabine +BSC over BSC alone - median OS 2.46 months (1.67-3.58), HR - 0.70 (95% CI - 0.38- 1.2), p = 0.30. Compared to only 15.1% (5/33) in BSC arm, the disease control rate (complete response + partial response + stable disease) at 6-8 weeks was 58.3% (21/36) in Erlotinib arm (p = 0.004) and 47.2% (17/36) in Capecitabine arm (p = 0.04). Grade III/IV toxicities were reported in 12 patients (33.3%) in Erlotinib arm (skin rash and diarrhea being most common at 8% each) and in 5 patients (13.8%) in Capecitabine arm (anemia and fatigue most common at 6 % each). No treatment related deaths were reported in either group. Addition of Erlotinib to BSC significantly improves OS in patients with unresectable/metastatic GBC, otherwise unfit to receive chemotherapy, with acceptable toxicity profile.

The feasibility of weekly paclitaxel in improving performance status(PS) of advanced non-small cell lung cancer (NSCLC) patients with poor performance status: A single-arm phase two trial.

e21155 Background: Treatment of driver mutation negative metastatic NSCLC with poor PS (Eastern Cooperative Oncology Group[ECOG] PS of ≥2) is controversial. Preliminary data suggests poor PS patients also benefit from chemotherapy, with toxicity being a valid concern. We hypothesize PS of a patient may improve with chemotherapy if poor PS is due to high tumor burden rather than comorbidities. We designed a phase II single arm study to assess the feasibility of using abbreviated chemotherapy to improve the PS of stage IIIC/IV NSCLC patients of ECOG PS≥2. Methods: Adult patients with age≤65 years, Charlson’s comorbidity index &lt; 9, serum albumin≥3.5g/dl, adequate bone marrow and organ function, &amp; ECOG PS≥2 as judged by the worst score of three independent physicians were administered 3 doses of weekly paclitaxel at 60mg/m2/dose. ECOG PS was again assessed at 4th week. Primary end point was an improvement in ECOG PS by 1 point at 4th week assessment. Secondary endpoints were toxicity by Common Terminology Criteria for Adverse Events (CTCAE v 5.0), quality of life(QOL)assessment at baseline and 4 weeks by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and its lung cancer module, EORTC QLQ-LC13. Optimal Simon’s 2 stage design was used. In the first stage, 18 pts were to be accrued; if ≤ 2 responses were observed the study would be stopped. Else, 25 additional pts would be recruited to a total of 43 patients. The null hypothesis would have been rejected if ≥ 7 responses were observed. This design yielded a type I error rate of 0.05 and 80% power. Results: A total of 46 patients were included in the study, median age 56years(interquartile range 54-59), 34(74%) male, 12(26%) had comorbid conditions, 34(74%) had extrathoracic disease, squamous cell carcinoma was the most common histology(41%). ECOG PS distribution shown in table. Overall, 11 out of 46 patients(24%) showed improved PS, fulfilling primary end point. Further 7 patients had improved in PS beyond the time point of 4 weeks. Due to improved PS, 16 patients(35%) were able to receive standard platinum doublet. Any grade toxicity was seen in 85% of patients and 20% had grade 3/4 (most common: anemia and diarrhea). At a median follow up of 4.8m (95 % CI: 3.27-14.9), the median progression free survival was 3.3 months (95% CI: 2.36-5.6) and median overall survival 6.8months (95% CI 2.47-8.8). QOL improved significantly for global QOL, role functioning, pain, dyspnea, insomnia, pain in chest, pain in other parts &amp; worsened for alopecia and sore mouth. Conclusions: Use of abbreviated chemotherapy is a useful, well tolerated strategy in carefully selected poor PS stage IIIC/IV NSCLC patients that leads to meaningful improvement in QOL. Clinical trial information: CTRI/2020/01/022617. [Table: see text]

72 - First line pembrolizumab for metastatic NSCLC in poor performance status patients

72 - First line pembrolizumab for metastatic NSCLC in poor performance status patients

Comparison of Different Tyrosine Kinase Inhibitors for Treatment of Poor Performance Status Patients with EGFR-Mutated Lung Adenocarcinoma

Simple SummaryEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments in patients with EGFR-mutated lung adenocarcinoma. However, the clinical data regarding EGFR-TKI efficacy in patients with poor performance status (PS ≥ 2) are limited. We reviewed the clinical outcomes and safety of EFGR-TKI use in patients with poor PS and identified the independent and favorable prognostic factors for progression-free survival and overall survival. We found that patients treated with 40 mg afatinib had better survival results, although only a non-significant trend toward superiority was observed in the multivariable analysis. Dose adjustment was an independent prognostic factor for PFS and OS. This study provided evidence of the use of EGFR-TKIs for patients with poor PS.The aim of this retrospective study was to investigate the tolerability and survival outcomes of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment in patients with a performance status ≥ 2. The data for 517 patients treated with EGFR-TKIs between January 2011 and January 2018 at a regional hospital in northern Taiwan were analyzed. Clinical and pathological features were collected, and univariate as well as multivariable analyses were undertaken to identify potential prognostic factors. The overall objective response rate, median progression-free survival (PFS), and median overall survival (OS) were 56.3%, 11.4 months, and 15.3 months, respectively. The mutation status (exon 19 deletion), locally advanced disease, dose adjustment, and the lack of liver and pleural metastasis were independent and favorable prognostic factors for PFS. Age < 60 years, mutation status (exon 19 deletion), dose adjustment, and lack of lung, liver, and no pleural metastasis were independent and favorable prognostic factors for OS. GFR-TKIs demonstrated acceptable efficacy and safety in the current cohort. Dose adjustment was identified as an independent prognostic factor for both PFS and OS, regardless of which EGFR-TKIs were used. The current research provided novel evidence of the clinical prescription of frontline EGFR-TKIs for EGFR-mutated lung adenocarcinoma patients with a PS score ≥2.

A Real-World Study on the Effectiveness and Safety of Pembrolizumab Plus Chemotherapy for Nonsquamous NSCLC

IntroductionThe real-world effectiveness of combination treatment with cytotoxic chemotherapy and programmed cell death protein-1 or programmed death-ligand 1 inhibitor for NSCLC, especially for the elderly (aged ≥75 y) or those with poor performance status (≥2), has not been fully elucidated. We investigated the real-world effectiveness and safety of this combination therapy in these populations. MethodsThis multicenter retrospective study evaluated patients who are chemo-naïve with advanced NSCLC who received a combination of platinum, pemetrexed, and pembrolizumab between December 2018 and June 2019. This was an updated prespecified secondary analysis with the primary objective of investigating the safety and effectiveness in this cohort. ResultsOverall, 299 patients were included. Multivariate analysis identified performance status (0–1) and programmed death-ligand 1 tumor proportion score (≥50%) as significant independent predictors of progression-free survival (p = 0.007, and p = 0.003, respectively). The incidence of severe adverse events (AEs) was higher in the elderly and those with poor performance status than in their younger and good performance status counterparts. A total of 71 patients developed AEs that led to treatment discontinuation, and AE-related treatment discontinuation occurred at a significantly higher rate in older patients (median [range]) (70 [46–82] y) than in younger patients (68 [31–84] y) (p <0.001). ConclusionsCombination treatment with pembrolizumab plus chemotherapy had low real-world effectiveness for poor performance status patients. Severe AEs occurred at a higher rate in the elderly and poor performance status patients, and the AE-related treatment discontinuation rate increased with age. Physicians should be cautious about using this regimen, especially in the elderly and poor performance status patients.

First-line osimertinib for poor performance status patients with EGFR mutation-positive non-small cell lung cancer: A prospective observational study.

The clinical outcomes of poor performance status (PS) patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive EGFR mutations. We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered osimertinib (80mg/day) as the initial treatment. Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred. Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies with larger cohorts are warranted.

Treatment Patterns and Outcomes of Patients with Double-Class Refractory or Triple-Class Refractory Multiple Myeloma: A Retrospective US Electronic Health Record Database Study

Introduction: Patients with relapsed/refractory multiple myeloma (RRMM) resistant to multiple drug classes remain a high unmet need population, despite advances in MM patient care. The objective of this study was to assess real-world treatment patterns and outcomes in patients with RRMM who had failed multiple prior lines of therapy (LOT) and were refractory to multiple drug classes to identify gaps in their treatment pathways.Methods: This longitudinal retrospective cohort study utilized the COTA de-identified real-world database derived from US electronic health records of partnered healthcare providers from Q3 1988 through Q1 2020. Adults with active RRMM previously exposed to a proteasome inhibitor (PI) and an immunomodulatory drug and who received ≥3 prior LOTs were identified. Patients were further categorized as refractory to a PI and an immunomodulatory drug (double-class refractory [DCR]) or additionally to an anti-CD38 monoclonal antibody (i.e. daratumumab; triple-class refractory [TCR]). Determining refractory status was based on International Myeloma Working Group criteria.Index LOT was a new LOT after evidence of DCR or TCR status following ≥3 (DCR) or ≥4 (TCR) prior LOTs. Patient characteristics described included Eastern Cooperative Oncology Group (ECOG) performance status, International Staging System (ISS) stage, cytogenetic risk, age, index date, sex, and follow up time. Treatment pattern assessments included treatments received before/during/after index LOT, reasons for discontinuation, refractory status, and retreatment characteristics. Patient outcomes (overall survival [OS], duration of treatment [DOT], and time to next therapy [TTNT]) were analyzed using Kaplan-Meier survival analysis methods.Results: After excluding patients who were aged <18 years at start of index LOT with no evidence of clinical activity and who participated in a clinical trial during index LOT, 381 (DCR) and 173 (TCR) patients were available for analysis. Median follow-up from index LOT initiation through end of data availability/death was 14 (DCR) and 8 (TCR) months. Demographic characteristics were consistent between DCR and TCR patients. Approximately half were aged ≥65 years (49% DCR; 53% TCR), majority had high-risk cytogenetics (56% DCR; 66% TCR) or prior autologous stem cell transplantation (>62%), and 14-16% had ISS stage III. Patients had a median of 3 (DCR) and 6 (TCR) prior LOTs.Prior to index LOT, bortezomib and lenalidomide were the most commonly received PI and immunomodulatory drug (received by >98% of DCR or TCR patients) and the most common PI and immunomodulatory drugs to which patients were refractory (71% and 84% DCR; 76% and 83% TCR, respectively).At index LOT, PI/immunomodulatory drug-based and daratumumab-based therapies remained the most common therapies. Bortezomib and lenalidomide had the longest time to refractory status and highest retreatment rates among DCR or TCR patients. Approximately 40% of TCR patients were retreated with daratumumab-based therapies after becoming refractory (Table).After index LOT, 70% of DCR and 58% of TCR patients continued to a subsequent LOT. Patients most frequently discontinued index LOT due to disease progression (59% DCR; 60% TCR), toxicity (23% DCR; 25% TCR), or doctor preference (14% DCR; 10% TCR). Median duration of gaps between LOTs generally were shorter than 1 month (Table).Median OS was 22.3 (DCR) and 11.6 (TCR) months. Median DOT was 3.3 (DCR) and 2.8 (TCR) months, and median TTNT was 4.1 (DCR) and 3.2 (TCR) months. In multivariate statistical analyses, inferior baseline ECOG performance scores, and high-risk cytogenetic abnormalities were associated with worse prognosis (higher risk of death, shorter DOT, and shorter TTNT) in DCR and TCR patients. Age was not a significant factor after adjusting for other baseline factors.Conclusions: Treatment options are limited for US patients with DCR and TCR RRMM. DCR and TCR patients were frequently retreated with a PI, an immunomodulatory drug, or daratumumab, despite refractoriness to these agents. Many DCR and TCR MM patients stopped active MM treatment after discontinuing index treatment. Patients with DCR and TCR MM have poor prognosis, especially among high cytogenetic risk and poor performance status patients. This study provides the benchmark for new therapies, like BCMA-targeted agents, to be tested in this population.Funding: GSK (Study 217353). [Display omitted] DisclosuresWang: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gorsh: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. DerSarkissian: Analysis Group, Inc.: Current Employment. Paka: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Bhak: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Boytsov: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Zichlin: GlaxoSmithKline: Research Funding; Analysis Group, Inc.: Consultancy, Current Employment. Sansbury: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Yee: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Ferrante: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Khanal: GlaxoSmithKline: Research Funding; Analysis Group, Inc.: Current Employment. Noman: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Duh: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study..

Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B)

BackgroundOsimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown.MethodsEnrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety.ResultsThirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations.ConclusionOsimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.

1446P Weekly hypofractionated palliative radiotherapy in poor performance status and elderly patients unfit for standard radiotherapy: Survival, acute and late toxicity outcomes

The aim of this study was to evaluate survival rates, acute and late toxicity after hypofractionated palliative radiotherapy (RT) in low performance status and elderly patients (pts), unfit for standard RT treatment.

Efficacy and Prognosis of First-Line EGFR-Tyrosine Kinase Inhibitor Treatment in Older Adults Including Poor Performance Status Patients with EGFR-Mutated Non-Small-Cell Lung Cancer.

IntroductionEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutated non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR-TKIs in older patients including poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) is seldom investigated.MethodsWe enrolled patients 65 years or older with EGFR-mutated Stage IIIB–IV NSCLC and evaluated the efficacy and prognosis of first-line EGFR-TKI treatment. Clinical and demographic characteristics were reviewed and analyzed, including age, sex, PS, smoking history, EGFR mutation type, treatment regimen, progression-free survival (PFS), and overall survival (OS).ResultsFrom January 2015 to December 2019, a total of 237 patients were included, 205 of whom were eligible for efficacy and outcome analyses. Among them, 91 (44.4%) were categorized as poor PS (2–4). Compared with patients categorized as good PS (0–1), those with poor PS were older (79 versus 75 years), had a higher proportion of brain metastases (41.8% versus 25.4%), more comorbidities (74.7% versus 54.4%), and more likely to be treated with first-generation TKIs (74.7% versus 57.0%). The PFS and OS were 17.1 and 26.7 months respectively in patients with good PS and 12.7 and 18.2 months in those with poor PS (both p < 0.001). In the multivariate analysis, good PS, <3 metastatic sites, and first-line treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS. A relatively younger age, good PS, < 3 metastatic sites, and no brain metastasis at diagnosis were associated with better OS.ConclusionIn older patients with EGFR-mutated NSCLC and receive EGFR-TKI treatment, a good PS and <3 metastatic sites at diagnosis were associated with a longer PFS and OS. In addition, afatinib as first-line treatment was associated with a longer PFS whereas a relatively younger age and no brain metastasis at diagnosis were associated with better OS.