Anti-angiogenic Therapy for Advanced Primary Pulmonary Lymphoepithelioma-like Carcinoma: a Retrospective Multicenter Study

Abstract Purpose: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of primary non-small cell lung cancer (NSCLC). Currently, there is still lack of research data on anti-angiogenic therapy of advanced PPLELC. The purpose of this study was to investigate the efficacy and safety of anti-angiogenic therapy combined with chemotherapy compared with traditional chemotherapy for these patients.Methods: Advanced PPLELC patients admitted to six grade A hospitals from January 2013 to January 2021 were selected. The patients received anti-angiogenic therapy combined with chemotherapy(AT group) or chemotherapy (CT group)alone.Results: A total of 65 patients were enrolled in this study, including 31 patients in the AT group treated with anti-angiogenic therapy combined with chemotherapy, and 34 patients in the CT group treated with chemotherapy alone. As of October 1, 2021, the median progression-free survival in the AT group was 11.2 months [95% confidence interval (CI), 5.9-16.5], The median progression-free survival in the CT group was 7.0 months [95%CI, 5.1-8.9][Hazard Ratio (HR), 0.49; 95%CI, 0.29-0.83; P=0.008]. The 1-year PFS rates were 41.9% and 17.6%, respectively. The ORR of two groups were 45.2% (95% CI, 0.27 to 0.64), 38.2% (95% CI, 0.21 to 0.56), (P = 0.571). The DCR of two groups were 93.5% (95% CI, 0.84 to 1.03), 88.2% (95% CI, 0.77 to 1.00), (P = 0.756).Conclusions: Among patients with advanced PPLELC, the progression free survival of patients with anti-angiogenic therapy combined with chemotherapy is better than that of patients with chemotherapy alone. Anti-angiogenic therapy combined with chemotherapy is an optional treatment scheme.

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Phase II Study of Vandetanib or Placebo in Small-Cell Lung Cancer Patients After Complete or Partial Response to Induction Chemotherapy With or Without Radiation Therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20

Journal of Clinical Oncology ◽

10.1200/jco.2007.12.3083 ◽

2007 ◽

Vol 25 (27) ◽

pp. 4278-4284 ◽

Cited By ~ 147

Author(s):

Andrew M. Arnold ◽

Lesley Seymour ◽

Michael Smylie ◽

Keyue Ding ◽

Yee Ung ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Partial Response ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival ◽

Median Progression Free Survival

PurposeThis double-blind randomized phase II trial examined whether vandetanib, an inhibitor of vascular endothelial and epidermal growth factor receptors, could prolong progression-free survival in responding patients with small-cell lung cancer.Patients and MethodsEligible patients with complete response (CR) or partial response (PR) to combination chemotherapy (± thoracic or prophylactic cranial radiation) received oral vandetanib 300 mg/d or matched placebo. With 100 patients and 77 events, the study had 80% power to detect an improvement in median progression-free survival from 4 to 6.5 months (one-sided, 10%-level test).ResultsBetween May 2003 and March 2006, 107 patients were accrued; 46 had limited disease and 61 extensive disease. There were fewer patients with a performance status of 0 (n = 11 v 20), and fewer had CR to initial therapy (n = 4 v 8) in the vandetanib arm. Vandetanib patients had more toxicity and required more dose modifications for gastrointestinal toxicity and rash. Asymptomatic Corrected QT interval (QTC) prolongation was observed in eight vandetanib patients. Median progression-free survival for vandetanib and placebo was 2.7 and 2.8 months, respectively (hazard ratio [HR], 1.01; 80% CI, 0.75 to 1.36; one-sided P = .51). Overall survival for vandetanib was 10.6 versus 11.9 months for placebo (HR, 1.43; 80% CI, 1.00 to 2.05; one-sided P = 0.9). In planned subgroup analyses, a significant interaction was noted (P = .01): limited-stage vandetanib patients had longer overall survival (HR, 0.45; one-sided P = .07) and extensive-stage vandetanib patients shorter survival compared with placebo (HR, 2.27; one-sided P = .996).ConclusionVandetanib failed to demonstrate efficacy as maintenance therapy for small-cell lung cancer.

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Topotecan and etoposide as salvage chemotherapy in patients with irinotecan- and platinum-failed small-cell lung cancer: A phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18177 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18177-18177

Author(s):

H. Choi ◽

B. Choi ◽

S. Shin ◽

S. Cheon ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Response Rate ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival ◽

Median Progression Free Survival ◽

Grade 3

18177 Background: The efficacy and safety of a combined regimen of topotecan and etoposide was tested in patients with relapsed or refractory small-cell lung cancer. Methods: From October 2003 to May 2005, 23 patients who have failed to the previous irinotecan and platinum chemotherapy received intravenous topotecan 1mg/m2 (day 1–5) followed by intravenous etoposide 80mg/m2 (day 1–3). Treatment was repeated every 21 days for a maximum of 6 cycles. Results: Twelve patients were refractory to first-line chemotherapy. Seventeen patients (73.9%) were male and the median age was 63 years. ECOG performance status was 0–1 in 13 (56.5%) patients. The median cycles of chemotherapy was 3. Twenty one patients were assessable for response evaluation. The overall response rate was 17.4% (0 CR, 4 PR, 7 SD, 10 PD) under the intent-to-treat analysis. After a median follow- up of 20.8 months, median progression free survival was 4.7 months and median overall survival was 9.5 months. The estimated 1-year survival rate was 38.7%. In sensitive relapsed patients, 2 achieved tumor response and median progression free survival and overall survival were 5.5 months and 14.5 months. All patients were assessable for toxicity and major toxicities were myelosuppression. Grade 3/4 neutropenia and thrombocytopenia occurred in 18 (78.3%) and 12 (52.2%) patients, respectively. Grade 3/4 febrile neutropenia occurred in 2 patients (8.7 %) and infection in 3 patients (13.0%). There was one treatment-related death due to pneumonia. Conclusions: This salvage regimen failed to demonstrate a considerable response rate compared with monotherapy for relapsed or refractory SCLC. However, the combination of topotecan and etoposide could be further studied for sensitive relapsed patients pretreated with irinotecan and platinum No significant financial relationships to disclose.

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Effectiveness and safety of pembrolizumab monotherapy in patients with locally advanced or metastatic non-small-cell lung cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211061117 ◽

2021 ◽

pp. 107815522110611

Author(s):

Rocio Tamayo-Bermejo ◽

Juan Carlos del Rio-Valencia ◽

Beatriz Mora-Rodriguez ◽

Isabel Muñoz-Castillo

Keyword(s):

Lung Cancer ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Small Cell ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Free Survival ◽

Median Progression Free Survival ◽

Third Line

Introduction Immunotherapy has become a standard treatment for lung cancer; the objective of this study was to evaluate the effectiveness, safety of pembrolizumab monotherapy in patients with advanced or metastatic non-small-cell lung cancer used in real-world clinical practice. Material and methods Retrospective observational study of every patient treated with pembrolizumab in our centre from January 2017 to June 2019. Outcomes collected: sex, age, Eastern Cooperative Oncology Group, programmed death receptor 1 level, previous metastatic line therapies, adverse events and smoking status. Results A total of 62 patients were reviewed. The median age was 62.34 ± 10.62 years, 48 (77.41%) were men and 91.93% of patients had Eastern Cooperative Oncology Group 0. The median dose administered was 170.5 mg (108 – 240 mg) and the median follow-up was 3 months (range: 1 – 38). A median of four cycles of pembrolizumab (range: 1 – 56) were administered as monotherapy. The reason for treatment discontinuation was mainly due to disease progression in 38.70% of patients or death in 30.64%. As first-line pembrolizumab monotherapy, median progression-free survival was 7.7 months (95% CI: 3.66 – 11.73) ( N = 33). With respect to patients who were treated in second–third-line treatment, median progression-free survival was 3.5 months (95% CI: 2.40 – 4.59) ( N=29). As to overall survival, pembrolizumab-treated patients as first-line treatment reached 19 months median OG (95% CI: 13.36 – 24.63) ( N = 33) and those treated in second–third-line treatment got 11 months (95% CI: 3.4 – 18.5). A total of 64.51% of patients presented some adverse events to pembrolizumab however, only, 9.38% of them were grade 3. Conclusion Pembrolizumab represents an effective and feasible alternative in terms of progression-free survival. It is a well-tolerated treatment option.

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Efficacy and safety of crizotinib in patients with anaplastic lymphoma kinase-positive stage IV non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20516 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20516-e20516 ◽

Cited By ~ 2

Author(s):

Ahmed M. Mohi El.Din ◽

Ayman Ahamd Rasmy

Keyword(s):

Lung Cancer ◽

Objective Response ◽

Stage Iv ◽

Progression Free Survival ◽

Small Cell ◽

Efficacy And Safety ◽

Small Cell Lung ◽

Free Survival ◽

Anaplastic Lymphoma ◽

Alk Positive

e20516 Background: Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting ALK, MET, and ROS1 tyrosine kinases. It was first approved by the Food and Drug Administration (FDA) in 2011 for treatment of patients in late-stage (locally advanced or metastatic) non-small cell lung cancer (NSCLC) with abnormal anaplastic lymphoma kinase (ALK) gene as detected by an FDA-approved test, as it confers improved progression-free survival comparison with chemotherapy. Methods: This is a retrospective chart review study of patients with stage IV ALK-positive NSCLC who attended the medical oncology department of Kuwait Cancer Control Centre (Kuwait) and King Fahad Specialist Hospital (Saudi Arabia) between January 2013 and May 2016. The efficacy and safety of crizotinib (250 mg orally, twice daily, with or without food.) were evaluated based on overall survival (OS), progression-free survival (PFS), Objective response rate (ORR), time to objective response, duration of response, and dose reduction or cessation because of crizotinib toxicity. Results: Twenty-three patients were involved in this study with a median age of 55.5 years and male-to-female ratio of 2.4:1 The median OS from initiation of crizotinib has not been reached; 1-year overall survival was 71.2%. Crizotinib treatment demonstrated median PFS of 9.6 months (95% CI, 3.0-24.1 months). The ORR was 70.9%. Complete response was achieved in 4.2% of patients, and partial response was achieved in 66.7% of patients. The most frequently reported adverse effects of crizotinib (Grade 1 / 2) were muscle ache, fatigue, nausea, vomiting, diarrhea, constipation, edema, elevated transaminases, bradycardia, and vision disorders. Grade 3 / 4 diarrhea was reported in 12.5% of patients. The proportion of patients who required dose reduction because of Crizotinib-induced bradycardia was 8.3% of patients. Conclusions: Crizotinib appears to be a very favorable option for treating patients with stage IV ALK-positive NSCLC. Crizotinib showed a very tolerable toxicity profile.

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First-line carboplatin plus pemetrexed with pemetrexed maintenance in HIV-positive patients with advanced non-squamous non-small cell lung cancer: the phase II IFCT-1001 CHIVA trial

European Respiratory Journal ◽

10.1183/13993003.02066-2019 ◽

2020 ◽

Vol 56 (2) ◽

pp. 1902066 ◽

Cited By ~ 1

Author(s):

Armelle Lavole ◽

Laurent Greillier ◽

Julien Mazières ◽

Isabelle Monnet ◽

Lize Kiakouama-Maleka ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Performance Status ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Free Survival ◽

Median Progression Free Survival ◽

Cd4 Lymphocyte

HIV infection is an exclusion criterion in lung cancer trials. This multicentre phase II trial aimed to assess feasibility, efficacy and safety of first-line carboplatin plus pemetrexed (CaP) followed by pemetrexed (P) maintenance in people living with HIV (PLHIV) with advanced non-squamous non-small cell lung cancer (NS-NSCLC).Four cycles of CaP were followed by P-maintenance therapy in patients with Eastern Cooperative Oncology Group performance status ≤2. The primary objective was a disease control rate (DCR) ≥30% after 12 weeks.Of the 61 PLHIV enrolled, 49 (80%) had a performance status of 0–1, and 19 (31%) had brain metastases. Median CD4 lymphocyte count was 418 cells·µL−1 (range 18–1230), median CD4 lymphocyte nadir was 169.5 cells·µL−1 (1–822); 48 (80%) patients were virologically controlled. Four-cycle inductions were achieved by 38 (62%) patients, and 31 (51%) started P-maintenance (median of 4.1 cycles (range 1–19)). The 12-week DCR was 50.8% (95% CI 38.3–63.4) and partial response rate 21.3%. Median progression-free survival and overall survival were 3.5 (95% CI 2.7–4.4) and 7.6 months (5.7–12.8), respectively. Patients with a performance status of 0–1 had the longest median progression-free survival (4.3 months, 95% CI 3.1–5.2) and overall survival (11.9 months, 95% CI 6.4–14.3). During induction, CaP doublet was well tolerated apart from grade 3–4 haematological toxicities (neutropenia 53.8%; thrombocytopenia 35.0%; anaemia 30.0%). Two fatal treatment-related sepses were reported. No opportunistic infections were experienced.In PLHIV with advanced NS-NSCLC, first-line four-cycle CaP induction followed by P-maintenance was effective and reasonably well-tolerated. Further studies should evaluate combination strategies of CaP with immunotherapy in PLHIV.

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Outcomes in Lung Cancer: 9-Year Experience From a Tertiary Cancer Center in India

Journal of Global Oncology ◽

10.1200/jgo.2016.006676 ◽

2017 ◽

Vol 3 (5) ◽

pp. 459-468 ◽

Cited By ~ 5

Author(s):

Aditya Navile Murali ◽

Venkatraman Radhakrishnan ◽

Trivadi S. Ganesan ◽

Rejiv Rajendranath ◽

Prasanth Ganesan ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival ◽

Median Progression Free Survival ◽

Advanced Stage Lung Cancer ◽

Stage Lung Cancer

Purpose Lung cancer is the most common cause of cancer mortality in the world. There are limited studies on survival outcomes of lung cancer in developing countries such as India. This study analyzed the outcomes of patients with lung cancer who underwent treatment at Cancer Institute (WIA), Chennai, India, between 2006 and 2015 to determine survival outcomes and identify prognostic factors. Patients and Methods In all, 678 patients with lung cancer underwent treatment. Median age was 58 years, and 91% of patients had non–small-cell lung cancer (NSCLC). Testing for epidermal growth factor receptor mutation was performed in 132 of 347 patients and 61 (46%) were positive. Results Median progression-free survival was 6.9 months and overall survival (OS) was 7.6 months for patients with NSCLC. Median progression-free survival was 6 months and OS was 7.2 months for patients with small-cell lung cancer. On multivariable analysis, the factors found to be significantly associated with inferior OS in NSCLC included nonadenocarcinoma histology, performance status more than 2, and stage. In small-cell lung cancer, younger age and earlier stage at presentation showed significantly better survival. Conclusion Our study highlights the challenges faced in treating lung cancer in India. Although median survival in advanced-stage lung cancer is still poor, strategies such as personalized medicine and use of second-line and maintenance chemotherapy may significantly improve the survival in patients with advanced-stage lung cancer in developing countries.

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