Clinical outcomes of patients with non-small cell lung cancer (NSCLC) receiving chemotherapy after immune checkpoint blockade.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9082-9082 ◽  
Author(s):  
Claud Grigg ◽  
Brian D. Reuland ◽  
Adrian G. Sacher ◽  
Randy Yeh ◽  
Naiyer A. Rizvi ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Objective Response ◽  
Poor Performance ◽  
Response Rates ◽  
Median Number ◽  
Immune Checkpoint Blockade ◽  
Poor Performance Status ◽  
Chemotherapy Response

9082 Background: Objective response rates (ORR) to chemotherapy beyond the first-line for advanced NSCLC are low (5-10%). Pre-clinical studies suggest that some chemotherapies may act, in part, through immune mediated mechanisms. Additionally, results from phase I/II studies of chemotherapy combined with immune checkpoint inhibitors (ICIs) suggest high response rates ( > 50%) and potential synergy. It is unknown whether chemotherapy is more efficacious when given after ICIs. Methods: We reviewed demographics, imaging, treatment history, and clinical course for all patients at our institution with a diagnosis of metastatic NSCLC who received at least one dose of nivolumab, pembrolizumab, atezolizumab, or durvalumab prior to December 8, 2016. Patients who received any subsequent chemotherapy were included for analysis. Objective response was determined by RECIST v1.1, and date of progression was determined radiographically or clinically (treatment discontinuation with documented clinical deterioration). Results: 145 patients received at least one dose of any ICI, and 38 patients received subsequent chemotherapy. The median age was 68 years (range 44-88). Six chemotherapy-naïve patients received carboplatin + pemetrexed +/- bevacizumab. There were 3 partial responses (PR) including one exceptional response that is ongoing after 2 years. Among 32 chemotherapy non-naïve patients, the median number of prior chemotherapy regimens was 2 (range 1-6). Post-ICI chemotherapy included docetaxel + ramucirumab (n = 12), vinorelbine (n = 7), gemcitabine-based chemotherapy (n = 6), carboplatin doublets (n = 4), pemetrexed + bevacizumab (n = 2), and paclitaxel (n = 1). Six patients had documented poor performance status and died within 1 month of starting treatment. The ORR was 25% (1CR, 7PR), median time to progression was 116 days, and 9 patients (28%) experienced stable disease (SD) or better lasting > 150 days. Exceptional responses occurred across regimens. Nine patients received a further line of chemotherapy, with 3 ongoing PR or SD lasting > 100 days. Conclusions: For NSCLC, chemotherapy response rates may be higher when administered after an ICI.

Immune Checkpoint Inhibitor Use Near the End of Life Is Associated With Poor Performance Status, Lower Hospice Enrollment, and Dying in the Hospital

2019 ◽  
Vol 37 (3) ◽  
pp. 179-184 ◽  
Author(s):  
Chad Glisch ◽  
Yuya Hagiwara ◽  
Stephanie Gilbertson-White ◽  
Yubo Gao ◽  
Laurel Lyckholm
Keyword(s):  
End Of Life ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Inhibitor Treatment

Background: Immune checkpoint inhibitors have changed the landscape of cancer care by increasing progression-free and overall survival in some patients with cancer. We evaluated use and variables contributing to immune checkpoint inhibitor treatment near the end of life. Methods: We studied 157 patients who received immune checkpoint inhibitors and died between January 2015 and December 2018. All patients had a palliative care consult any time between starting an immune checkpoint inhibitor and death. Univariate and multivariate models were used to examine variables related to immune checkpoint inhibitor use near the end of life. Results: Among 157 patients studied, 42 (27%) received a dose of immune checkpoint inhibitor in the last 30 days of life. Those who received treatment in the last 30 days of life had lower hospice enrollment (19 [45%] vs 78 [69%], P = .007) and higher rates of dying in the hospital (23 [56%] vs 33 [29%], P = .002). The percentage of patients with Eastern Cooperative Oncology Group (ECOG) ≥3 at the time of last immune checkpoint inhibitor dose was higher in the group that received immune checkpoint inhibitor treatment in the last 30 days of life (11 [26%] vs 9 [8%], P = .003). Lack of traditional chemotherapy after immune checkpoint inhibitor, ECOG ≥3, and lack of hospice enrollment were independently associated with receiving immune checkpoint inhibitor in the last 30 days of life. Conclusion: Immune checkpoint inhibitor use in the last 30 days of life is common and associated with poor performance status, lower hospice enrollment, and dying in the hospital.

Outcomes of patients (pts) with metastatic urothelial cancer (mUC) and poor performance status (PS) receiving anti-PD(L)1 agents.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4525-4525
Author(s):  
Ali Raza Khaki ◽  
Leonidas Nikolaos Diamantopoulos ◽  
Ang Li ◽  
Michael Edward Devitt ◽  
Alexandra Drakaki ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Wholesale Price ◽  
Poor Performance ◽  
Wald Test ◽  
Median Number ◽  
Hospital Death ◽  
Poor Performance Status ◽  
Metastatic Urothelial Cancer ◽  
Ecog Ps

4525 Background: Anti-PD(L)1 immune checkpoint inhibitors (ICI) prolong overall survival (OS) after platinum chemotherapy in mUC. However, clinical outcomes in pts with poor PS at time of ICI initiation are unknown. We hypothesized that ICI initiation in pts with ECOG PS 2-3 would be associated with worse outcomes vs. pts with ECOG PS < 2, and impact death location. Methods: A retrospective cohort study in 8 institutions identified pts with mUC who received ICI. Demographic, clinicopathologic, treatment (tx) patterns, tx response, and outcomes were collected. Primary endpoint: overall response rate (ORR). Secondary endpoints: median (m) OS in pts receiving ICI as 1st and 2nd line (1L, 2L); odds of dying in hospital (vs elsewhere) for pts receiving ICI (vs no tx) within 30 days of death; and estimated drug cost for pts with ICI within 30 days of death based on average wholesale price. Unadjusted logistic regression was used to assess association between ORR and ECOG PS (2-3 vs < 2) and wald test was used to compare mOS between ECOG PS (2-3 vs < 2). Results: 194 consecutive pts (30% women, 41% never smokers, median age at diagnosis 69) treated with ICI for mUC were identified. Median number of total tx lines was 2; all pts received ≥1 ICI line (6 pts received 2 ICI lines); 97, 79, 17 and 7 pts received ICI in 1L, 2L, 3L and 4L, respectively; 26% pts with ICI in 1L and 2L had ECOG PS 2-3. ORR and mOS are shown in table. Among 106 pts who died, 96 had available death location; of those, 8% received ICI within 30 days of death. Starting ICI within 30 days of death (vs no tx) was associated with higher odds of hospital death (OR 6.05, 95%CI 1.3-27.6). Estimated average ICI cost/pt within 30 days of death was $1400.58. Conclusions: Pts with ECOG PS 2-3 at time of ICI initiation had similar ORR vs ECOG PS < 2 but worse mOS. ICI initiation within 30 days from death was associated with higher likelihood of hospital death. ICI may not circumvent the negative prognostic role of poor PS, so biomarker-based pt selection is critical. Limitations include lack of adjustment for selection bias and other confounders at time of ICI initiation; data validation is ongoing. [Table: see text]

Weekly chemotherapy instead of best supportive care alone must be considered for patients of small cell lung cancer with poor performance status.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21102-e21102
Author(s):  
Gunjan Shrivastav ◽  
Alok Gupta ◽  
Neha Sonthwal ◽  
Suhas Kirti Singla ◽  
Tarun Mohindra ◽  
...  
Keyword(s):  
Chemotherapy Regimen ◽  
Performance Status ◽  
Objective Response ◽  
Poor Performance ◽  
Median Number ◽  
Best Supportive Care ◽  
Poor Performance Status ◽  
Weekly Chemotherapy ◽  
Group A ◽  
Group B

e21102 Background: Many patients of Small Cell Lung Cancer (SCLC) present with advanced age & comorbidities. Although chemotherapy may benefit these patients, therapy is denied due to treatment toxicities. We studied tolerability and efficacy of weekly Etoposide with carboplatin in patients unfit for 3-weekly regimen to analyze the hypothesis if small dose weekly chemotherapy can replace the current standard of care of best supportive care (BSC) alone in patients with poor performance status (PS). Methods: We retrospectively studied consecutive patients of SCLC treated between January 2015- December 2017. Based on team’s assessment, patients received either Etoposide100 mg/m2 (Day 1,2,3) + Cisplatin25 mg/m2 (Day 1,2,3) (or Carboplatin AUC5 Day 1) q 21 days OR Etoposide100 mg/m2 + Carboplatin(AUC2)q weekly OR BSC. Responses at 6-9 weeks of therapy and toxicities were studied according to RECIST 1.1 and CTCAEv4 criteria respectively. Results: 66 patients were diagnosed with SCLC. 24 patients received 3-weekly chemotherapy regimen (Group A). Of the 42 unfit patients, 21(50 %) received weekly chemotherapy regimen (Group B). Median age was higher in Group B ( 66 vs 61 yrs ) and Co-morbidities (≥ 2)were also more in Group B, 53 vs 33 %. Furthermore, Group B had more brain metastases (38 vs 21 %) but there was equal distribution of liver metastases and SVCO (4 patients each group). Altogether Group B had worse prognostic patients. In Group A the median number of chemotherapy cycles received were 4.5 (1-8) over a median duration of 3.37 months (0.75 - 6) while in group B the median number of chemotherapy cycles were 2 (1-5) over 1.5 months (0.5 - 3.75). G-CSF was required in 22(92%) in Group A and 15(71%) in Group B. Grade 3-4 toxicity and Febrile neutropenia were seen in 11(46%) and 7(29%) patients in Group A respectively and 8(38.1%) and 7(33%) patients in Group B respectively. Progressive disease was seen in 3(13%) and 6(29%) patients in group A and B respectively. Objective response was seen in 14(59%) and 9(43%) in Group A and B respectively. Clinical benefit rate (CBR) (Objective response + Stable disease) was 75% in Group A and 57% in Group B. Among patients with brain metastasis, CBR was 60% in Group A and 50% in Group B. This was better than most patients that are not offered treatment. Conclusions: Although 3 weekly doublet remains a better regimen, weekly etoposide and platinum is a valid option for patients unfit for standard regimen with no excess toxicity. Clinical benefit is seen irrespective of poor prognostic features.

scholarly journals Clinical Effectiveness of Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer with a Poor Performance Status

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1273
Author(s):  
Kyoichi Kaira ◽  
Hisao Imai ◽  
Atsuto Mouri ◽  
Ou Yamaguchi ◽  
Hiroshi Kagamu
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
First Line ◽  
Lung Cancer Patients

Immune checkpoint inhibitors (ICIs) are standard treatments for patients with lung cancer. PD-1/PD-L1 or CTLA4 antibodies are chosen as the first-line therapy, contributing to the long-term survival and tolerability. Unlike molecular targeting agents, such as gefitinib, lung cancer patients with a poor performance status (PS) display unsatisfactory clinical improvements after ICI treatment. Several previous reports also demonstrated that the PS is identified as one of the most probable prognostic factors for predicting poor outcomes after ICI treatment. However, first-line pembrolizumab seemed to be effective for lung cancer patients with a PS of 2 if PD-L1 expression was greater than 50%. Currently, the induction of ICIs in patients with lung cancer with a poor PS is controversial. These problems are discussed in this review.

scholarly journals Immune checkpoint inhibitors in patients with solid tumors and poor performance status

Medicine ◽  
2021 ◽  
Vol 100 (13) ◽  
pp. e25115
Author(s):  
Akhil Kapoor ◽  
Vanita Noronha ◽  
Vijay M. Patil ◽  
Nandini Menon ◽  
Amit Joshi ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status

Phase II trial of pemetrexed (P) and gemcitabine (G) as first-line chemotherapy for elderly and/or poor performance status patients with stage IIIB/IV non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17031-17031
Author(s):  
J. Blakely ◽  
F. Schnell ◽  
P. Kaywin ◽  
M. Keaton ◽  
B. Fortner ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Poor Performance ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Stage Iiib ◽  
Poor Performance Status ◽  
Female Ratio ◽  
Grade 3

17031 Background: Pemetrexed and gemcitabine have shown to be active agents in the treatment of locally advanced or metastatic NSCLC with favorable toxicity profiles. A recent phase I study examined a biweekly schedule of P and G in combination in order to establish a maximum tolerated dose in solid tumors. (Dudeck, A. ASCO 2004 Abstract 2141.) This established the dose for this study. Methods: After informed consent all patients received biweekly cycles of P 500 mg/m2 IV 10 minutes before G 1500 mg/m2 IV. A maximum of 12 cycles was planned for stable or responding patients. All patients received vitamin B12 1000 μg and folic acid 1000 mg 7 days prior to the initiation of treatment and continued through treatment. Entry criteria include measurable stage IIIB/IV NSCLC by RECIST criteria, age ≥65 years and ECOG 0–2 or <65 years and ECOG of 2. A total of 40 patients are scheduled to be enrolled. Primary endpoint is objective response rate. Results: To date, 19 of 29 enrolled patients have data available for analysis. The median age is 71 (range 61–85). 2 had stage IIIB and 17 stage IV, median number of sites of disease is 2. Male/Female ratio was 10/9. Performance status was as follows ECOG 0 = 3 patients, 1 = 12 patients, 2 = 4 patients. 3 patients had grade 3 or 4 neutropenia with only 1 patient having neutropenic fever. There were no grade 3 or 4 anemias or thrombocytopenias. One patient had grade 3/4 nausea; there were no other severe non-hematologic toxicities. 14 patients were evaluable for response with 3 achieving PR (21%), 10 with SD (71%) (median number of cycles 7) and 1 with PD (7%). Conclusion: Pemetrexed and gemcitabine in combination biweekly has substantial activity with a favorable toxicity profile for patients with advanced NSCLC who are elderly or have poor performance status. The study is expected to be completed and fully evaluable by ASCO. No significant financial relationships to disclose.

Impact of performance status on response and survival among patients receiving checkpoint inhibitors for advanced solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12028-12028 ◽  
Author(s):  
Mridula Krishnan ◽  
Benjamin A. Teply ◽  
Fang Yu ◽  
Robin High
Keyword(s):  
Median Survival ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Poor Performance ◽  
Response Rates ◽  
Poor Performance Status ◽  
Head Neck Cancer ◽  
Advanced Malignancy ◽  
Ecog Ps

12028 Background: Clinical trials leading to the approval of immune checkpoint inhibition (ICI) have almost exclusively been performed in patients with good performance status (ECOG PS of 0-1). However, ICI remains an attractive option for patients with advanced tumors and poor performance status, considering their overall tolerability. While use of ICI in patients with poor PS (ECOG PS of 2 or greater) has been rapidly adopted, whether these patients derive the same benefits as expected in the studied populations is largely unknown. We therefore performed an institutional retrospective analysis of all patients treated with palliative single agent anti-PD1 or anti-PDL1 to determine response and survival for those with poor performance status. Methods: We retrospectively identified patients with advanced solid tumor malignancies who were treated with ICI monotherapy with palliative intent at our institution between 2015-2019. The primary objective was to compare overall survival (OS) for patients with good PS (ECOG PS 0-1) with those with poor PS (ECOG PS 2 or 3-4). The log-rank test compared the survival among patients with different ECOG PS. In addition, we used a proportional hazards model to assess association between ECOG PS and the OS with adjustment for age, gender, and smoking status. A secondary objective was to compare overall response rates (ORR) of the three ECOG PS groups which were evaluated with a binary rate model. Results: We identified 266 patients treated with ICI, 87 with NSCLC, 34 with melanoma, 33 with RCC, 24 with bladder cancer, 22 with head/neck cancer, and the rest with other histologies. 187 (70%) were ECOG PS 0-1, 62 (23%) were ECOG PS 2, and 17 (7%) were ECOG PS 3-4. 89 of these patients (33%) were still alive at time of last follow-up. Across all tumor types, patients with ECOG PS 0-1 had superior survival compared to ECOG PS 2 (median survival 12.4 months vs 4.6 months, HR 0.41, p < 0.001). Median survival for ECOG PS 3-4 was lower at 2.3 months. The ORR for ECOG PS 0-1 (23%) was significantly higher to that of ECOG PS 2 (6%, p = 0.02). ORR for ECOG PS 3-4 was 12%. Conclusions: Despite the appeal of ICI for patients with advanced malignancy and poor performance status, outcomes were poor. Survival and objective response rates for patients with ECOG PS 2 and higher were significantly worse than those with ECOG PS 0-1. ICI treatment comes with cost, including potentially forgoing early hospice referral or optimal support at the end of life. Prospective trials defining the activity and role of ICI in poor PS are urgently needed.

scholarly journals Treatment with therapeutic anticoagulation is not associated with immunotherapy response in advanced cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Paul Johannet ◽  
Amelia Sawyers ◽  
Nicholas Gulati ◽  
Douglas Donnelly ◽  
Samuel Kozloff ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Coagulation Cascade ◽  
Advanced Cancer Patients ◽  
Clinical Endpoints

Abstract Background Recent preclinical data suggest that there may be therapeutic synergy between immune checkpoint blockade and inhibition of the coagulation cascade. Here, we investigate whether patients who received immune checkpoint inhibitors (ICI) and were on concomitant anticoagulation (AC) experienced better treatment outcomes than individuals not on AC.Affiliation: Kindly confirm if corresponding authors affiliation is identified correctly.The corresponding author's affiliation is correct. Methods We studied a cohort of 728 advanced cancer patients who received 948 lines of ICI at NYU (2010–2020). Patients were classified based on whether they did (n = 120) or did not (n = 828) receive therapeutic AC at any point during their treatment with ICI. We investigated the relationship between AC status and multiple clinical endpoints including best overall response (BOR), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of bleeding complications.Affiliations: Journal instruction requires a country for affiliations; however, this is missing in affiliations 1 to 5. Please verify if the provided country is correct and amend if necessary.The country is correct for all affiliations (1 - 5). Results Treatment with AC was not associated with significantly different BOR (P = 0.80), ORR (P =0.60), DCR (P =0.77), PFS (P = 0.59), or OS (P =0.64). Patients who received AC were significantly more likely to suffer a major or clinically relevant minor bleed (P = 0.05). Conclusion AC does not appear to impact the activity or efficacy of ICI in advanced cancer patients. On the basis of our findings, we caution that there is insufficient evidence to support prospectively evaluating the combination of AC and immunotherapy.

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