scholarly journals Favorable Outcome in Patients with Pheochromocytoma and Paraganglioma Treated with 177Lu-DOTATATE

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 909 ◽  
Author(s):  
Achyut Ram Vyakaranam ◽  
Joakim Crona ◽  
Olov Norlén ◽  
Dan Granberg ◽  
Ulrike Garske-Román ◽  
...  
Keyword(s):  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Favorable Outcome ◽  
First Line ◽  
Ki 67 ◽  
First Line Therapy ◽  
Line Therapy ◽  
Radiological Response ◽  
Low Toxicity ◽  
Grade 3

Peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising therapy for neuroendocrine tumors (NETs). This retrospective cohort study aimed to assess the outcome of PRRT for 22 patients with histopathologically confirmed pheochromocytoma (PCC) and paraganglioma (PGL), of which two were localized and 20 metastatic. Radiological response utilized response evaluation criteria in solid tumors 1.1 and toxicity was graded according to common terminology criteria for adverse events version 4. Median 4 (range 3–11) 7.4 GBq cycles of 177Lu-DOTATATE were administered as first-line therapy (n = 13) or because of progressive disease (n = 9). Partial response (PR) was achieved in two and stable disease (SD) in 20 patients. The median overall survival (OS) was 49.6 (range 8.2–139) months and median progression-free survival (PFS) was 21.6 (range 6.7–138) months. Scintigraphic response >50% was achieved in 9/19 (47%) patients. Biochemical response (>50% decrease) of chromogranin A was found in 6/15 (40%) patients and of catecholamines in 3/12 (25%) patients. Subgroup analysis showed Ki-67 <15% associated with longer OS (p = 0.013) and PFS (p = 0.005). PRRT as first-line therapy was associated with increased OS (p = 0.041). No hematological or kidney toxicity grade 3–4 was registered. 177Lu-DOTATATE therapy was associated with favorable outcome and low toxicity. High Ki-67 (≥15%) and PRRT received because of progression on previous therapy could constitute negative predictive factors for OS.

Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 2006-2012 ◽  
Author(s):  
Jim Cassidy ◽  
Stephen Clarke ◽  
Eduardo Díaz-Rubio ◽  
Werner Scheithauer ◽  
Arie Figer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hand Foot Syndrome ◽  
Grade 3

PurposeTo evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).Patients and MethodsThe initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 × 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.ResultsThe intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 × 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.ConclusionXELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

Influence of antibiotic therapy (ATB) on oncological outcomes of metastatic non-small cell lung cancer (mNSCLC) patients treated with chemo-immunotherapy (CIT).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3080-3080
Author(s):  
James Clark ◽  
Biagio Ricciuti ◽  
Anita Bolina ◽  
Deepti Venkatraman ◽  
Thomas Newsom-Davis ◽  
...  
Keyword(s):  
Performance Status ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
The United States ◽  
Response Evaluation ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Multivariable Analyses

3080 Background: ATB exposure is proven to worsen response and survival in immunotherapy recipients. However, its influence on outcomes from CIT is currently undefined. Methods: We conducted a retrospective, multi-centre observational study including 77 mNSCLC patients who received pembrolizumab, pemetrexed and carboplatin CIT as first-line therapy for mNSCLC, between December 1, 2018 and January 1, 2020 in 3 academic referral centres in Europe and in the United States. We documented ATB exposure in the 30 days prior to CIT commencement (pATB) or concurrently (cATB) until CIT cessation. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from commencement of CIT, and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1). Results: We enrolled 77 patients, 41 of whom were female (n = 53%) with adenocarcinoma (n = 73, 95%), performance status (PS) 0-1 (n = 69, 90%) PD-L1 Tumour Proportion Score < 50 (n = 57, 74%). Median OS was 16.4 months (95%CI 8.4-24.4), median PFS was 6.7 months (95%CI 5.7-7.6). ORR was 48% including 1 complete (1%) and 36 partial responses (47%). Eleven patients (14%) received pATB, with penicillin/cephalosporins (p/c, n = 7, 63%) for <7 days (n = 10, 90%). Thirty-five patients (45%) received cATB with p/c (n = 11, 40%) for <7 days (n = 28, 80%). Most common indication for ATB was peri-procedure prophylaxis in pATB (n = 7, 63%) and suspected febrile neutropenia in cATB (n = 14, 40%). pATB (p = 0.004) but not cATB (p = 0.85) predicted for worse OS (19.6 vs 6.5 months, Hazard Ratio [HR] 2.9 95%CI 1.3-6.3). Neither pATB nor cATB predicted for PFS or ORR (p > 0.05). Multivariable analyses confirmed pATB (HR 2.3 95%CI 1.1-5.5, p = 0.05) to predict for OS independent of PD-L1 status, PS and cATB. pATB+/- groups were balanced with regards to age, gender, PS nor PD-L1 status (p > 0.05). Conclusions: Whilst cATB does not compromise outcome from CIT, this study reproduces the detrimental effects observed for pATB exposure in immunotherapy recipients. Mechanistic verification of the immune-biologic foundations underlying this association is urgently warranted.

scholarly journals Multicenter Analysis of Treatment Outcomes for Systemic Therapy in Well Differentiated Grade 3 Neuroendocrine Tumors (NET G3)

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1936
Author(s):  
Leonidas Apostolidis ◽  
Arianna Dal Buono ◽  
Elettra Merola ◽  
Henning Jann ◽  
Dirk Jäger ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Progression Free Survival ◽  
First Line ◽  
Treatment Protocols ◽  
First Line Therapy ◽  
Line Therapy ◽  
Multicenter Analysis ◽  
Net G3 ◽  
Well Differentiated ◽  
Grade 3

Well-differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications. Commonly applied first-line chemotherapy protocols with cisplatin or carboplatin in combination with etoposide (PE) are less effective in NET G3 than NEC. Suggested alternative treatment protocols have not been studied in first-line therapy of NET G3 so far. We performed a retrospective analysis of patients with NET G3 in the databases of 3 German cancer centers. Out of 142 patients, 136 patients received palliative first-line therapy: overall response rate (ORR) was 35.1% for PE (n = 37), 56.4% for FOLFOX (n = 39), 27.3% for temozolomide/capecitabine (TEM/CAP) (n = 22), 45.0% for streptozotocin/5-fluorouracil (STZ/5-FU) (n = 20), and 16.7% for other (n = 18). Median progression-free survival (PFS) for PE was 6.9 months. Compared to PE, PFS in the other treatment groups was 6.9 months for FOLFOX (p = 0.333), 12.0 months for TEM/CAP (p = 0.093), 4.8 months for STZ/5-FU (p = 0.919), and 14.1 months for other (p = 0.014). In a univariate setting, all non-PE patients combined showed a significantly prolonged PFS vs. PE (9.0 months; p = 0.049) which could not be confirmed in a multivariate analysis. In conclusion, NET G3 with FOLFOX showed the highest ORR, and with TEM/CAP showed the longest PFS. Further prospective evaluation of the optimal therapeutic strategy for this tumor entity is needed.

Assessment for markers of poor prognosis in a real-world evidence study of treatment patterns in patients with HR+/HER2- locally advanced or metastatic breast cancer in Korea and Taiwan.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13083-e13083
Author(s):  
Diego Novick ◽  
Narayan Rajan ◽  
Rebecca Ming-Huei Cheng ◽  
Sae Young Lee ◽  
Dong Hyun Koo ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
First Line ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

e13083 Background: To assess how patient characteristics impact treatment patterns and real-world effectiveness among patients with hormone receptor (HR+)/human epidermal growth receptor 2-negative (HER2-) locally advanced and metastatic breast cancer (ABC) in Korea and Taiwan. Methods: We conducted a retrospective chart review comprising 227 female patients aged ≥ 18 years and diagnosed HR+/HER2- ABC in Korea and Taiwan between 2015-2017. Those having at least one of the following characteristics, shown previously to negatively impact prognosis, formed the poor prognostic cohort (PPC): ECOG PS > 0, not bone-only disease, liver metastases, or negative PgR status. Anonymized data on patient characteristics, treatment pathways, progression-free survival, and grade 3 or higher adverse events (AEs) of interest was abstracted. Descriptive statistics and Kaplan Meier methods were used to assess the outcomes. Results: The mean (range) age was 57.1 (29 - 83) years. A total of 193 (85.0%) patients were PPC. Endocrine regimens were the most frequent first-line therapies used by 50.3% and 67.6% of patients in the PPC and non-PPC cohorts, respectively. Chemotherapy regimens were used by 25.9% and 17.6% as initial systemic therapy and by 60.1% and 35.3% at any time following diagnosis of ABC, for PPC and non-PPC, respectively. The median progression-free survival time, based on first-line therapy, was 8.3 (95%CI: 6.9 – 10.4) months for PPC versus 11.5 (95%CI: 5.5 – 12.0) months in non-PPC. The proportion of patients with at least 1 grade 3 or higher AEs of interest during first-line therapy was higher in the PPC cohort compared to the non-PPC cohort, 54.4% vs. 44.1% respectively. The most common AEs reported were leukopenia, asthenia/fatigue and neutropenia occurring in 27.5%, 28.0% and 20.7% of the PPC cohort and 23.5%, 2.9%, and 14.7% of the non-PPC cohort, respectively. Conclusions: The existence of one or more poor prognostic factors is associated with a higher chemotherapy use any time following diagnosis of ABC, as well as lower median progression-free survival and a higher likelihood of having an adverse event during first line therapy, compared to non-PPC cohort. These results suggest that patient poor prognostic characteristics can be drivers for therapy selection.

Endostatin combined with chemotherapy as first-line therapy for stage IV melanoma patients: A phase II clinical study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20003-e20003
Author(s):  
C. Cui ◽  
Z. Chi ◽  
X. Yuan ◽  
L. Si ◽  
X. Sheng ◽  
...  
Keyword(s):  
Sinus Bradycardia ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Ii Clinical Study ◽  
Melanoma Patients ◽  
Grade 3 ◽  
Stage Iv Melanoma

e20003 Background: To observe the efficacy and safety of rh-endostatin injection (Endostar) combined with chemotherapy as first line therapy for stage IV melanoma patients. Methods: From March 2007-March 2008, 20 metastatic melanoma patients were enrolled. Endostar (15 mg d1–14) combined with dacarbazine (250 mg/m2 d1–5) or temozolomide (300 mg d 1–5) and fotemustine (100 mg/m2 d6) were given every 28days. Response, toxicity and progression free survival(PFS) were analyzed. Results: Among 20 evaluable cases, with mean cycle 2.7±0.80, four achieved partial response, six stable disease, with response rate 20.0% (4/20) and clinical benefit rate 50.0% (10/20). The median PFS reached 4.5 months (95% CI: 3.85–6.9 months), overall survival 8.5 months (95% CI: 5.62–8.54 months), with 6 months PFS rate 35% (7/20), and 6 months survival rate 65% (13/20). The Grade 3/4 toxicity was mainly myelosuppression, 40% (8/20). One patient ceased the treatment because of sinus bradycardia. Conclusions: Endostar combined with chemotherapy show its efficacy on melanoma patients and may prolong PFS. No significant financial relationships to disclose.

Endostar plus gemcitabine/cisplatin (GP) with maintenance endostar as first-line therapy for advanced non-small cell lung cancer (NSCLC): Preliminary results of a phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18033-e18033
Author(s):  
You Lu ◽  
Meijuan Huang ◽  
Qingxia Fan ◽  
Qi Wu ◽  
Jin Wang ◽  
...  
Keyword(s):  
Survival Rate ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3

e18033 Background: Endostar is a recombinant human endostatin. We conducted a multi-centre trial to investigate the efficacy and safety of Endostar plus GP with maintenance Endostar as first- line therapy for advanced NSCLC Methods: Chemotherapy-naïve patients with histologically or cytologically confirmed, measurable, stage ‡W NSCLC were enrolled from 11 centers in China. All patients received gemcitabine 1,000 mg/m2 (days 1 and 8) plus cisplatin 25 mg/m2 (days 1-3) every 21 days. Patients achieving objective response or disease stabilization following initial 2 cycles of GP were given Endostar (15 mg) on days 1–14 every 21 days in combination with another 2 cycles of GP. Then, patients who did not progress received maintenance endostar (15 mg) on days 1–14 every 21 days until disease progression or unacceptable toxicity. The primary was progression-free survival (PFS). Secondary endpoints were treatment-related toxicity and median overall survival (OS). Results: Between Oct.2008 and Sep. 2010, we enrolled 85 patients (median age: 52.2 years; median KPS score: 80; stage IV with M1b: 94.1%; adenocarcinoma: 64.6%). 48 (56.5%) patients complete 4 cycles of GP plus 2 cycles of Endostar and 33(38.8%) patients were treated with maintenance Endostar. For 38 patients receiving maintenance therapy, median PFS throughout the study period by independent review was 5.97 month and 1-year survival rate was 75.8%. Median PFS were 3.97 months for all 85 patients, while 1-year survival rate was 64.7%. No treatment related death occurred. 28(32.9%) patients had at least one grade 3/4 adverse events; the grade 3/4 hematologic toxicity included anemia in 32.9%, thrombocytopenia in 25.9%, neutropenia in 4.7% of patients. The grade 3/4 non-hematologic toxicities included nausea/vomiting in 18.8%, rash in 5.9%, hepatic impairment in 3.5%, diarrhea in 1.2%, hemorrhage in 1.2% of patients. Conclusions: This regimen, involving maintenance Endostar, didn’t significantly improve PFS in advanced NSCLC patients as compared to historic control although associated acceptable toxicity has been demonstrated

Randomized phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous NSCLC.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7512-7512
Author(s):  
Suresh S. Ramalingam ◽  
Mikhail Shtivelband ◽  
Ross A. Soo ◽  
Carlos H. Barrios ◽  
Anatoly Makhson ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
And Gender ◽  
Ecog Ps

7512 Background: Linifanib is a potent and selective inhibitor of VEGF and PDGF receptors with modest single-agent activity in NSCLC. We evaluated the combination of linifanib with carboplatin (C) and paclitaxel (P) for first-line therapy of advanced non-squamous NSCLC. Methods: Patients (pts) with stage IIIB/IV, non-squamous NSCLC, stratified by ECOG PS and gender, were randomized to receive up to six 3-wk cycles of C (AUC 6 mg/ml/min) and P (200 mg/m2) with daily placebo (Arm A), linifanib 7.5 mg (Arm B), or linifanib 12.5 mg (Arm C). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), 12 m survival rate, and objective response rate (ORR). Safety was assessed by NCI-CTCAE v3.0. Results: 138 pts were randomized at 37 sites in 6 countries. Baseline characteristics were: median age, 61 y; men, 57%; smoker, 84%. Efficacy results are shown in the table. Thrombocytopenia was the only Grade 3/4 AE significantly higher on linifanib (Arm B: 16.7%; Arm C: 29.8%) vs. placebo (2.1%). Other adverse events (AEs) related to the dose of linifanib were diarrhea, thrombocytopenia, hypertension, weight loss, palmar-plantar erythrodysaesthesia syndrome, and hypothyroidism. Analysis of samples for predictive biomarkers including serum VEGF and placental growth factor are underway. Conclusions: The addition of linifanib to chemotherapy was tolerable at the doses tested and resulted in a significant improvement in PFS, with a modest survival improvement for Arm C in first-line therapy of advanced non-squamous NSCLC. [Table: see text]

FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study

2004 ◽  
Vol 22 (2) ◽  
pp. 229-237 ◽  
Author(s):  
Christophe Tournigand ◽  
Thierry André ◽  
Emmanuel Achille ◽  
Gérard Lledo ◽  
Michel Flesh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Study ◽  
Grade 3

Purpose In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B). Patients and Methods Previously untreated patients with assessable disease were randomly assigned to receive a 2-hour infusion of l-LV 200 mg/m2 or dl-LV 400 mg/m2 followed by a FU bolus 400 mg/m2 and 46-hour infusion 2,400 to 3,000 mg/m2 every 46 hours every 2 weeks, either with irinotecan 180 mg/m2 or with oxaliplatin 100 mg/m2 as a 2-hour infusion on day 1. At progression, irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm B). Results Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI (P = .99). Median second progression-free survival (PFS) was 14.2 months in arm A versus 10.9 in arm B (P = .64). In first-line therapy, FOLFIRI achieved 56% response rate (RR) and 8.5 months median PFS, versus FOLFOX6 which achieved 54% RR and 8.0 months median PFS (P = .26). Second-line FOLFIRI achieved 4% RR and 2.5 months median PFS, versus FOLFOX6 which achieved 15% RR and 4.2 months PFS. In first-line therapy, National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis, nausea/vomiting, and grade 2 alopecia were more frequent with FOLFIRI, and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6. Conclusion Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.

Pan-cancer evaluation of homologous repair deficiency somatic mutations and response to first-line anti-neoplastic therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10535-10535
Author(s):  
Jessica A Lavery ◽  
Samantha Brown ◽  
Gregory J. Riely ◽  
Philippe L. Bedard ◽  
Ben Ho Park ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
De Novo ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Major Mechanism ◽  
First Line Therapy ◽  
Oncogenic Mutation ◽  
Line Therapy ◽  
Response To Chemotherapy

10535 Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]

scholarly journals The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangyun Liu ◽  
Yixuan Zhang ◽  
Miaowen Liu ◽  
Ruoxin Xu ◽  
Fengming Yi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients. Methods We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS). Results We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia. Conclusions The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.

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