Camrelizumab combined with microwave ablation improves the objective response rate in advanced non-small cell lung cancer

PURPOSE A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

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Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.2.360 ◽

1994 ◽

Vol 12 (2) ◽

pp. 360-367 ◽

Cited By ~ 597

Author(s):

T Le Chevalier ◽

D Brisgand ◽

J Y Douillard ◽

J L Pujol ◽

V Alberola ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Response Rate ◽

Randomized Study ◽

Objective Response ◽

Multicenter Trial ◽

Small Cell ◽

Survival Duration ◽

Small Cell Lung

PURPOSE We designed a prospective randomized trial to compare vinorelbine and cisplatin (NVB-P) with vindesine and cisplatin (VDS-P) and to evaluate whether the best of these regimens affords a survival benefit compared with vinorelbine alone (NVB), an outpatient regimen, in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-five centers included 612 patients in this study: 206 on NVB-P, 200 on VDS-P, and 206 on NVB. Vinorelbine was administered at a dose of 30 mg/m2 weekly, cisplatin at 120 mg/m2 on days 1 and 29 and then every 6 weeks, and vindesine at 3 mg/m2 weekly for 6 weeks and then every other week. Treatment was continued until progression or toxicity. Four percent of the patients entered were ineligible and 59% had metastatic disease. RESULTS An objective response rate was observed in 30% of patients in the NVB-P arm versus 19% in the VDS-P arm (P = .02) and 14% in the NVB arm (P < .001). The median duration of survival was 40 weeks in the NVB-P arm, compared with 32 weeks in the VDS-P arm and 31 weeks in the NVB arm. Comparison of survival among the three groups demonstrated an advantage for NVB-P compared with VDS-P (P = .04) and NVB (P = .01). Neutropenia was significantly higher in the NVB-P group (P < .001), and neurotoxicity was more frequent with VDS-P (P < .004). CONCLUSION Since our results have demonstrated that NVB-P yields a longer survival duration and a higher response rate than VDS-P or NVB alone, with acceptable toxicity, this combination should be considered a relevant regimen in advanced NSCLC.

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ALK and EGFR mutation analysis in a phase II trial of cisplatin/pemetrexed in Japanese patients with advanced nonsquamous non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18017 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18017-e18017

Author(s):

Kyohei Kaburaki ◽

Fumiyoshi Ohyanagi ◽

Azusa Tanimoto ◽

Toshio Sakatani ◽

Yuko Kawano ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Response Rate ◽

Fusion Gene ◽

Objective Response ◽

Small Cell ◽

Wild Type ◽

Small Cell Lung

e18017 Background: Recently, ethnic differences and genotypes such as EGFR mutation (EGFRm) or fusion gene (ALK translocation: ALKt) are important factors in non-small cell lung cancer (NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard care for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen has not been well examined in Japanese Nsq NSCLC patients (pts); furthermore, the difference in efficacy between genotypes was not thoroughly examined. Therefore, the present study was conducted to evaluate the efficacy of the CP regimen in Japanese Nsq NSCLC pts, and to determine whether EGFRm and ALKt impacted the treatment. Methods: This study was conducted from May 2009 to December 2010. Pts were eligible for this study if they had histologically or cytologically confirmed recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and adequate organ function. Pts received C (75 mg/m2) plus P (500 mg/m2) on day 1 every 3 weeks. Of the 50 pts initially enrolled, 49 were evaluated, and 43 tumor samples were available for analysis. Most pts were male (80%), and 80% of the pts had adenocarcinoma. The primary endpoint was the response rate that was evaluated according to RECIST. EGFRm was examined using PCR-based methods, and the ALK fusion protein was examined using a highly sensitive IHC method in the available tumor specimens. Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment. Results: The objective response rate and disease control rate in all pts were 44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months, and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was identified. Among the 43 samples, the following mutations were identified: 9 EGFRm (21%), 5 ALKt (12%), and 29 wild-type (67%). Objective response was observed in 6 (66.7%) EGFRm, 2 (40%) ALKt, and 13 (44.8%) wild-type. Conclusions: Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment.

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Clinical Study of Gefitinib for Non-Small Cell Lung Cancer

Proceedings of Anticancer Research ◽

10.26689/par.v5i6.2687 ◽

2021 ◽

Vol 5 (6) ◽

pp. 47-51

Author(s):

Yang Li

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Tumor Markers ◽

Cell Lung Cancer ◽

Adverse Reactions ◽

Response Rate ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung ◽

Single Drug

Objective: To evaluate the clinical efficacy of gefitinib in non-small cell lung cancer. Methods: A total of 45 patients with non-small cell lung cancer who received treatment in Taizhou Second People’s Hospital from January 2018 to January 2020 were selected as the subjects in this study, in which all of them were treated with gefitinib. Its efficacy and safety were evaluated. Results: The objective response rate was 53.33% and the disease control rate was 84.44%. After treatment, the levels of tumor markers were measured again, of which the levels of CA125 and CEA were significantly lower than before (P < 0.05). After treatment, the patients’ CD3+, CD4+, and CD4+/CD8+ were significantly lower than those before treatment, and CD8+ was significantly higher (P < 0.05). Conclusion: Gefitinib, which is a targeted therapy for non-small cell lung cancer, can reduce the level of serum tumor markers and improve the immune function. The curative effect is good, but more emphasis should be on the adverse reactions caused by a single drug use.

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VAC chemotherapy with valproic acid for refractory/relapsing small cell lung cancer: a phase II study

ERJ Open Research ◽

10.1183/23120541.00029-2015 ◽

2015 ◽

Vol 1 (2) ◽

pp. 00029-2015 ◽

Cited By ~ 2

Author(s):

Thierry Berghmans ◽

Jean-Jacques Lafitte ◽

Arnaud Scherpereel ◽

Lieveke Ameye ◽

Marianne Paesmans ◽

...

Keyword(s):

Lung Cancer ◽

Valproic Acid ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Response Rate ◽

Phase Ii Study ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung

Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study was to determine whether epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine and cyclophosphamide (VAC) regimen improves 6-month progression-free survival (PFS).Patients with pathologically proven SCLC refractory to prior platinum derivatives and etoposide were eligible. After central registration, patients received VAC plus daily oral valproic acid.64 patients were registered, of whom six were ineligible. Seven patients did not receive any CT, leaving 51 patients assessable for the primary end-point. The objective response rate was 19.6%. Median PFS was 2.8 months (95% CI 2.5–3.6 months) and 6-month PFS was 6%. Median survival time was 5.9 months (95% CI 4.7–7.5 months). Toxicity was mainly haematological, with 88% and 26% grade 3–4 neutropenia and thrombopenia, respectively.Despite an interesting response rate, the addition of valproic acid to VAC did not translate into adequate PFS in relapsing SCLC or SCLC refractory to platinum–etoposide.

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Randomized Phase II Trial of a Toll-Like Receptor 9 Agonist Oligodeoxynucleotide, PF-3512676, in Combination With First-Line Taxane Plus Platinum Chemotherapy for Advanced-Stage Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.12.5807 ◽

2008 ◽

Vol 26 (24) ◽

pp. 3979-3986 ◽

Cited By ~ 118

Author(s):

Christian Manegold ◽

Donald Gravenor ◽

Donald Woytowitz ◽

Jörg Mezger ◽

Vera Hirsh ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Response Rate ◽

Objective Response ◽

Small Cell ◽

Toll Like Receptor ◽

Small Cell Lung ◽

First Line ◽

Platinum Chemotherapy

PurposeThis study assessed the efficacy of the combination of standard taxane plus platinum chemotherapy with the synthetic Toll-like receptor 9–activating oligodeoxynucleotide PF-3512676 in patients with non–small-cell lung cancer (NSCLC).Patients and MethodsChemotherapy-naive patients with stage IIIB to IV NSCLC were randomly assigned (one to two ratio) to receive four to six cycles of taxane/platinum chemotherapy alone or with 0.2 mg/kg of subcutaneous PF-3512676 on days 8 and 15 of each 3-week cycle. The primary end point was objective response rate (ORR).ResultsBaseline demographics were similar between treatment arms, although significantly more patients in the PF-3512676 arm had stage IV disease (85% compared with 62% in the chemotherapy-alone arm). The modified intent-to-treat analysis (n = 111) demonstrated a 38% ORR (confirmed and unconfirmed) in the PF-3512676 arm (n = 74) and 19% in the chemotherapy-alone arm (n = 37) by investigator evaluation. Blinded, independent radiologic review for 90 patients showed a similar trend in confirmed response rate (19% and 11%, respectively). Median survival was 12.3 months in the PF-3512676 arm and 6.8 months in the chemotherapy-alone arm, and 1-year survival was 50% and 33%, respectively. Mild to moderate local injection site reactions and flu-like symptoms were the most common PF-3512676–related adverse events, but grade 3/4 neutropenia, thrombocytopenia, and anemia were all reported more commonly for patients in the PF-3512676 arm.ConclusionThe addition of PF-3512676 to taxane plus platinum chemotherapy for first-line treatment of NSCLC improves objective response and may improve survival. Confirmatory phase III trials are ongoing.

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Efficacy of single-site radiotherapy plus PD-1 inhibitors vs PD-1 inhibitors for oligometastatic non-small cell lung cancer

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03849-3 ◽

2021 ◽

Author(s):

Peiliang Wang ◽

Tianwen Yin ◽

Kaikai Zhao ◽

Jinming Yu ◽

Feifei Teng

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Response Rate ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Small Cell ◽

Single Site ◽

Small Cell Lung ◽

Metastatic Sites

Abstract Purpose Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aimed to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity. Methods We retrospectively identified oligometastatic NSCLC (< 4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS). Results Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of RT to ICI therapy significantly increased the best ORR from 31.2% to 50.8% (p = 0.015). The out-of-field (abscopal effect) response rate could reach 41.3% (95%CI 26.5%–56.1%) in the ICI plus RT group. Median PFS was 8.9 months (95%CI 4.7–13.1 months) with ICI alone versus 13.8 months (95%CI 9.5–18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.556; p = 0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients aged < 65 years (p = 0.016), patients with ECOG PS = 0 (p = 0.048), and patients with 1–2 metastatic sites (p = 0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm. Conclusion Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.

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Poziotinib for Patients With HER2 Exon 20 Mutant Non–Small-Cell Lung Cancer: Results From a Phase II Trial

Journal of Clinical Oncology ◽

10.1200/jco.21.01113 ◽

2021 ◽

pp. JCO.21.01113

Author(s):

Yasir Y. Elamin ◽

Jacqulyne P. Robichaux ◽

Brett W. Carter ◽

Mehmet Altan ◽

Don L. Gibbons ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Objective Response Rate ◽

Response Rate ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung ◽

Platinum Based Chemotherapy ◽

Exon 20

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with HER2 exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study. PATIENTS AND METHODS Patients with advanced HER2 exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles. The primary end point was objective response rate per RECIST version 1.1. Confirmatory scans were performed at least 28 days from initial radiologic response. RESULTS Thirty patients received poziotinib treatment. At baseline, 90% of patients received prior platinum-based chemotherapy and 53% had two lines or more prior systemic therapies. As of data cutoff on March 1, 2021, the confirmed objective response rate was 27% (95% CI, 12 to 46). Responses were observed across HER2 exon 20 mutation subtypes. The median duration of response was 5.0 months (95% CI, 4.0 to not estimable). The median progression-free survival was 5.5 months (95% CI, 4.0 to 7.0). The median overall survival was 15 months (95% CI, 9.0 to not estimable). The most common grade 3 treatment-related adverse events were skin rash (47%) and diarrhea (20%). There was one possible treatment-related death because of pneumonitis. CONCLUSION Poziotinib showed promising antitumor activity in patients with HER2 exon 20 mutant NSCLC including patients who had previously received platinum-based chemotherapy.

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Cisplatin versus cisplatin plus etoposide in the treatment of advanced non-small-cell lung cancer. Lung Cancer Working Party, Belgium.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.8.1087 ◽

1989 ◽

Vol 7 (8) ◽

pp. 1087-1092 ◽

Cited By ~ 88

Author(s):

J Klastersky ◽

J P Sculier ◽

G Bureau ◽

P Libert ◽

P Ravez ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Response Rate ◽

Randomized Study ◽

Objective Response ◽

Working Party ◽

Small Cell ◽

Small Cell Lung ◽

Significant Difference

We conducted a randomized study comparing the survival after treatment with cisplatin (120 mg/m2) or cisplatin plus etoposide (100 mg/m2 on days 1, 2, and 3) in 162 evaluable patients with advanced non-small-cell lung cancer (NSCLC). No statistically significant difference in survival was detected; the median survival was 26 and 22 weeks, respectively, for patients receiving cisplatin and for those receiving cisplatin plus etoposide. The objective response rate was 19% for cisplatin and 26% for the combination; the corresponding response rates were 17% and 43% in patients with limited disease. No significant differences were detected between the two study arms as far as toxicity was concerned, except for alopecia and granulocytopenia, which occurred more frequently in patients treated with cisplatin plus etoposide.

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The Application of Combined Immune Checkpoint Inhibitor Modalities in Previously Treated Non-Small Cell Lung Cancer Patients and the Associations Thereof With the Lung Immune Prognostic Index

Frontiers in Oncology ◽

10.3389/fonc.2021.690093 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ting Zhang ◽

Xue Yang ◽

Jing Zhao ◽

Lixia Xia ◽

Qiyuan Wang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint Inhibitor ◽

Response Rate ◽

Objective Response ◽

Prognostic Index ◽

Small Cell ◽

Small Cell Lung ◽

Previously Treated

BackgroundImmune checkpoint inhibitor (ICI) monotherapy remains the standard of care for patients with previously treated non-small cell lung cancer. However, few reports have compared the clinical benefits of second-line ICIs alone with those of ICIs combined with other therapies, including anti-angiogenesis therapy or chemotherapy.MethodsPatients with previously treated advanced non-small cell lung cancer who received ICIs were retrospectively reviewed. The progression-free survival (PFS), overall survival, objective response rate, disease control rate, and safety were assessed. Complete blood cell counts and serum lactate dehydrogenase (LDH) levels were measured before and after ICI treatment.ResultsOf 120 patients, 75 were treated with ICI monotherapy, 26 with ICIs plus anti-angiogenic therapy (ICI+A), and 19 with ICIs plus chemotherapy (ICI+C). The objective response rate was significantly higher in the ICI+C group (57.9%) than ICI monotherapy (26.3%) and ICI+A (31.8%) groups. The depth of response was significantly greater in the ICI+C (-35.1%) than ICI+A (−2.04%) and ICI monotherapy (3.963%) groups. ICI+C afforded a better PFS compared with the ICI monotherapy and ICI+A groups (8.5 vs. 4.6 and 4.1 months, respectively). Notably, the pre- and post-treatment peripheral neutrophil/lymphocyte ratios and serum LDH levels were negatively correlated with the PFS of the entire cohort. More importantly, the pretreatment lung immune prognostic index (neutrophil/lymphocyte ratio ≥ 4 and LDH level ≥ upper limit of normal) satisfactorily predicted the responses to ICI-based strategies. Adverse events (AEs) occurred in 65.3%, 92.3%, and 94.7% of patients in the ICI monotherapy, ICI+A, and ICI+C groups, respectively. Grade 3–5 AEs were more common in the combination therapy groups (ICI+A, 19.2%; ICI+C, 21%; ICI monotherapy, 4%).ConclusionIn second-line settings and beyond, ICIs combined with chemotherapy prolonged survival, with tolerable AEs. Addition of anti-angiogenic agents to ICIs did not afford any additional benefits. Further prospective studies are warranted.

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