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Simple Summary: The clinical significance of nivolumab plus ipilimumab in patients with recurrence after chemoradiotherapy followed by durvalumab remains unclear. We investigated the efficacy and safety of nivolumab plus ipilimumab in patients who relapsed after chemoradiotherapy followed by durvalumab. The 6- and 12-month PFS rates for nivolumab plus ipilimumab for relapse after durvalumab were 46.7% and 36.4%, indicating a long-tail plateau. Nivolumab plus ipilimumab was particularly effective in patients treated with durvalumab for 6 months or more. Therefore, nivolumab plus ipilimumab is a promising treatment option for patients who have relapsed after CCRT–durvalumab, with good tolerability. Nivolumab plus ipilimumab showed promising efficacy in patients with metastatic non-small-cell lung cancer (NSCLC). The efficacy of the nivolumab plus ipilimumab combination regimen in NSCLC patients who relapse after durvalumab consolidation following concurrent chemoradiotherapy (CCRT) has not been determined. Between January 2021 and June 2022, clinical data were retrospectively extracted from the medical records of patients with NSCLC who received nivolumab plus ipilimumab after CCRT and durvalumab consolidation. A total of 30 patients were included in this analysis. The median number of durvalumab treatment cycles was 11. Median PFS and OS with nivolumab plus ipilimumab were 4.2 months (95% confidence interval [CI]: 0.7–7.7) and 18.5 months (95% CI: 3.5–33.5), respectively. The 6-month and 12-month PFS rates were 46.7% (95% CI: 28.8–64.5) and 36.4% (95% CI: 19.0–53.7). In multivariate analysis, a significant correlation was observed between a durvalumab treatment duration of 6 months or more and PFS (p = 0.04) as well as OS (p = 0.001). Grade 3 adverse events, including pneumonitis, dermatitis, and colitis, occurred in 10% of the patients. This study suggests that nivolumab plus ipilimumab is effective, especially in patients who have received durvalumab for 6 months or more, and tolerable for patients who relapsed after durvalumab following CCRT. [ABSTRACT FROM AUTHOR]

Background: The relationship between antinuclear antibody (ANA) and the efficacy of programmed death-1 (PD-1) blockade remains controversial. Here, we investigated the prognostic significance of ANA titer in patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab monotherapy as the first-line treatment, compared with that of platinum-based chemotherapy with PD-1 blockade. Methods: Our clinical data based on the ANA titer (1:80) were retrospectively reviewed for patients with advanced NSCLC, who were treated with first-line pembrolizumab monotherapy and platinum-based chemotherapy with PD-1 blockade. Immunohistochemical staining for tumor-infiltrating lymphocytes such as CD4, CD8 and Foxp3 was performed. Results: Among 106 patients treated with pembrolizumab, 19 (17.9%) tested high for ANA. Progression-free survival (PFS) and overall survival (OS) were significantly better in patients with high ANA than in those with low ANA, and high ANA was identified as an independent prognostic predictor, particularly in the subgroup with programmed death ligand-1 (PD-L1) ≥ 50%. However, no statistically significant difference in PFS and OS based on the ANA titer was observed in 59 patients treated with combinational chemotherapy and immunotherapy. High numbers of intratumoral Foxp3 and stromal CD8 were significantly associated with low ANA. Conclusions: Assessment of preexisting ANA titers was useful to prognose PD-1 blockade as a first-line setting, particularly for the PD-L1 ≥ 50% subgroup, but not in the case of combined immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Chemoradiotherapy followed by durvalumab is the standard treatment for the patients with local advanced non‐small cell lung cancer (NSCLC). There is a real‐world data about the management of adverse events, such as pneumonitis, according to the different institutions. Here, we present the experience regarding the management of adverse events after the initiation of durvalumab as daily practice. Methods: From July 2018 to August 2019, 41 patients with locally advanced NSCLC, who underwent chemoradiotherapy followed by durvalumab, were retrospectively analyzed in the study using our medical records. Results: The median age of patients was 72 years (range: 51–80 years). A total of 33 patients were male and eight were female, and 40 patients (98%) received a total radiation dose of 60 Gy as concomitant chemoradiotherapy. The median V20 for the entire cohort was 18.9% (range: 3.5–29.9). Any adverse events during chemoradiotherapy and durvalumab were observed in 32 patients (78.0%), while three patients (7.3%) experienced grade 3 toxicities. In total, 25 (61.0%) patients experienced pneumonitis, four (9.8%) thyroid dysfunction, three (7.3%) myopathy, two (4.9%) rash or eruption, one (2.4%) bowel disease and one (2.4%) malaise. Grade 3 pneumonitis, thyroid dysfunction and myopathy were observed in one (2.4%), one (2.4%) and one (2.4%), respectively. A total of 22 (53.7%) patients were unable to continue durvalumab due to pneumonitis. However, durvalumab was finally readministered to six patients. Conclusions: The adherence to lung dose constraints such as V20 as well as close treatment monitoring are a prerequisite for the management of pneumonitis during maintenance therapy with durvalumab. [ABSTRACT FROM AUTHOR]

Background: After the cessation of immune checkpoint inhibitor (ICI) therapy due to an immune-related adverse event (irAE), it remains unclear whether retreatment with ICI is more effective than its discontinuation. To explore the clinical significance of its retreatment, patients with non-small cell lung cancer (NSCLC) who had treatment interruption of nivolumab due to irAEs were identified and the clinical differences between discontinuation and retreatment with nivolumab were retrospectively reviewed.Methods: 49 (26%) of 187 patients treated with nivolumab experienced the cessation of treatment due to a serious irAE. Retreatment was chosen in 21 patients (retreatment cohort), while 28 patients discontinued treatment (discontinuation cohort).Results: The most common irAEs requiring treatment cessation in 49 patients included pneumonitis (59.2%), adrenal insufficiency (8.2%), liver dysfunction (8.2%) renal dysfunction (8.2%), colitis (6.1%), hypothyroidism (4.1%), and rash (2.0%). The frequency of grade 3 or 4 initial irAEs did not differ between the retreatment and discontinuation cohorts; however, the incidence of renal dysfunction and colitis was higher in the retreatment cohort than in the discontinuation cohort. Retreatment with nivolumab displayed an overall response rate of 15%, without a significant increase in irAEs. The median overall survival and progression-free survival did not differ significantly between the retreatment and discontinuation cohorts, irrespective of the efficacy of prior nivolumab.Conclusions: Retreatment exhibited a slightly higher efficacy without a significant increase in irAEs; however, the clinical significance of retreatment and discontinuation was similar in NSCLC patients that led to treatment interruption due to any irAE after initial nivolumab. [ABSTRACT FROM AUTHOR]

Whether primary prophylactic pegylated‐granulocyte‐colony stimulating factor (PEG‐G‐CSF) should be administered immediately after the initiation of ramucirumab plus docetaxel (DR) to prevent the occurrence of febrile neutropenia (FN) is unclear. Our retrospective study aimed to elucidate whether PEG‐G‐CSF could control the occurrence of FN as a result of DR in patients with previously treated non‐small‐cell lung cancer. Thirty‐three patients with previously treated non‐small‐cell lung cancer who had received DR were eligible for our analysis. Of the 33 patients, 29 received prophylactic PEG‐G‐CSF immediately after DR, but none developed FN. However, FN was observed in 2 (50%) of the 4 patients that were not administered PEG‐CSF. The overall response and disease control rates in the 29 patients with prophylactic PEG‐GSF were 31% and 62%, respectively. The median progression‐free and overall survival rates of the patients with and without prophylactic PEG‐GSF were 177 and 163 days (P = 0.20), and 628 and 274 days (P = 0.13), respectively. Primary prophylactic PEG‐G‐CSF suppressed the occurrence of FN secondary to the administration of DR. [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor (VEGF) has been identified as one of the resistant mechanisms to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). However, the relationship between the efficacy of osimertinib and protein expression of VEGF family members in patients with advanced non‐small cell lung cancer (NSCLC) harboring EGFR mutations remains unclear. Methods: A total of 76 patients with advanced NSCLC with EGFR major mutations (del19 or L858R) receiving first‐line osimertinib were eligible as the osimertinib (Osi) group, whereas 43 patients receiving first‐ or second‐generation EGFR‐TKIs were compared with the control group. The expression of vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial growth factor C (VEGF‐C) in the tumor specimens was analyzed using immunohistochemistry. Results: VEGFR2 and VEGF‐C were highly expressed in 65.8% and 51.3% of patients, respectively, in the Osi group, and 69.7% and 76.7%, respectively, in the control group. High VEGFR2 and VEGF‐C levels were significantly associated with poor performance status (PS) and female sex, respectively. In the Osi group, patients with co‐high expression of VEGFR2 and VEGF‐C showed significantly worse progression‐free survival (PFS) and overall survival (OS) than those without co‐high expression. In del19, VEGFR2 was a significant predictor of PFS and OS and independent predictor of OS in multivariate analysis. In L858R, co‐high expression of VEGFR2 and VEGF‐C was identified as a significant predictor of PFS and OS and independent predictor of PFS. Conclusion: VEGFR2 and VEGF‐C are highly expressed in EGFR‐mutant NSCLC cells. Increased expression of VEGFR2 was identified as a significant prognostic factor in patients with EGFR del19 mutation who received osimertinib, whereas co‐high expression of VEGFR2 and VEGF‐C was a significant predictor for those with EGFR L858R mutation. [ABSTRACT FROM AUTHOR]

Challenge tests involving chemical stimulation by inhalation of capsaicin or citric acid are currently used to assess cough sensitivity. We investigated the clinical usefulness of cough challenge tests based on mechanical stimulation. A total of 347 patients (126 men and 221 women) were enrolled in the study, including 161 patients with asthma, 116 with cough-variant asthma, 27 with acute upper respiratory tract viral infections, 25 with acute bronchitis, four with pneumonia, three with chronic bronchitis and 11 with cough of unknown aetiology. Three modes of mechanical stimulation were assessed: the cervical trachea was compressed softly with the fingers several times (tracheal compression test); the trachea was stretched by retroflexion of the neck for 5 s (tracheal stretch test); and a vibrating tuning fork was placed on the cervical trachea for 20 s (tuning fork test). The relationships between phonation-induced cough and the results of these tests were assessed. The cough detection rate was 27.7% with the tracheal compression test, 39.8% with the tracheal stretch test and 36.9% with the tuning fork test. An itchy sensation with or without cough was noted by about 50% of subjects undergoing each of the tests. Provocation of cough and an itchy sensation during each test was significantly more frequent in subjects with phonation-induced cough. Tests were usually negative after improvement of the cough with treatment. Mechanical stimulation of the cervical trachea is a feasible cough challenge test that may be useful for evaluating disease activity. The clinical usefulness of three cough challenge tests based on mechanical stimulation was evaluated. Mechanical stimulation of the cervical trachea is easy to perform in daily practice and may be a useful method for evaluating disease activity in patients with cough. [ABSTRACT FROM AUTHOR]

Objectives: Programmed death-1(PD-1)/programmed death ligand-1 (PD-L1) antibodies have clinical benefits for cancer patients facing immune-related adverse events (irAEs). However, the effect of steroid use on the prognosis of patients with non-small cell lung cancer (NSCLC) receiving PD-1 blockade remains unclear. Methods: NSCLC patients with complete response (CR)/partial response (PR) or stable disease (SD)/not evaluable (NE) status plus progression-free survival (PFS) of 180 days after PD-1 blockade from December 2015 to December 2018 were retrospectively registered in our study and were divided into two groups: those with and without systemic steroid use for irAEs. Results: In total, 126 patients who had benefitted from PD-1 blockade were enrolled in our study; among them, 44 received systemic steroids for irAEs, and 82 had no adverse events or, if they did, did not receive systemic steroids. Among the 44 patients requiring steroids, interstitial lung disease (ILD), adrenal insufficiency, diarrhea, and liver dysfunction were observed in 19, 9, 4, and 4 patients, respectively. More side effects were observed in the group treated by steroids. The median PFS and overall survival (OS) in patients with and without systemic steroid use were 11.7 and 16.0 months (p < 0.037) and 35.0 and 41.0 months (p < 0.28), respectively. In univariate and multivariate analyses of survival, systemic steroid treatment for irAEs was significantly associated with PFS. The occurrence of ILD, adrenal insufficiency, and fever was significant in patients who used systemic steroids for irAEs. Conclusions: Patients administered systemic steroids for irAEs due to PD-1 blockade treatment exhibited shorter PFS than those who were not. Systemic steroids might affect survival after PD-1 blockade even for patients who once acquired its clinical benefit. [ABSTRACT FROM AUTHOR]

Background: Durvalumab is a standard drug used during maintenance therapy after chemoradiotherapy in patients with locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the clinical benefits of durvalumab after chemoradiotherapy in patients with LA-NSCLC with a performance status (PS) of 2 and/or aged > 75 years. As daily carboplatin plus concurrent thoracic radiotherapy is recommended for elderly patients according to guideline, the current phase II study aims to investigate the effect of daily carboplatin plus radiotherapy followed by durvalumab for patients with stage III NSCLC who have a PS of 2 and/or are older.Methods: Daily carboplatin plus radiotherapy followed by durvalumab is performed for the patients with stage III NSCLC who have a PS of 2 and/or are older. This is a trial in progress manuscript.Study Treatment: Daily, intravenous, low-dose carboplatin (30 mg/m2 in a 30-min infusion) is administered to patients 1 h before radiotherapy for the first 20 fractions. Radiotherapy for all patients consisted of 60 Gy administered as 30 fractions over 6 weeks. Durvalumab at a dose of 10 mg/kg/body is intravenously administered every 2 weeks for up to 12 months after chemoradiotherapy.Exploratory Assessment: In the future, an exploratory investigation will be performed to determine whether the combined assessment of T-cell markers, PD-L1 expression, and tumor mutation burden could predict the outcomes of the regimen.Discussion: The results of our study will exhibit the efficacy and tolerability of durvalumab as maintenance therapy after daily carboplatin plus radiotherapy.Trial Registration: During the first registration (before induction chemoradiotherapy), 70 patients will be included; then, we include 58 patients during the second registration (before durvalumab treatment after chemoradiotherapy). https://jcrb.niph.go.jp/ .Primary Endpoint: The primary endpoint of the current study is the 12-month progression-free survival (PFS) rate after the initiation of durvalumab.Secondary Endpoints: The secondary endpoints are the feasibility, objective response, PFS, overall survival, and adverse events. [ABSTRACT FROM AUTHOR]

Introduction: Biomarkers for predicting the outcome of ipilimumab plus nivolumab (Nivo-Ipi) treatment in cancer patients have not been identified. Herein, we investigated the prognostic significance of inflammatory and nutritional markers in patients with advanced non-small cell lung cancer (NSCLC) receiving Nivo-Ipi. Methods: Our study retrospectively analyzed 101 patients with advanced NSCLC who received Nivo-Ipi at a single institution. Inflammatory and nutritional indices were correlated with patient outcomes and included the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score (GPS). Results: The NLR significantly correlated with the PLR, SII, PNI, ALI, and GPS. Regarding therapeutic efficacy, the NLR, SII, and PNI predicted a partial response, and all indices predicted progressive disease. In subgroup analyses, the SII, PNI, and ALI predicted the outcome of patients with adenocarcinoma, whereas only the PNI predicted the outcome of patients with non-adenocarcinoma. The PNI and SII were the most useful indices in patients with a programmed death ligand-1 expression level of <1% and ≥1%, respectively. Conclusion: The NLR, PLR, SII, PNI, ALI, and GPS were significantly associated with the outcome of Nivo-Ipi treatment in patients with NSCLC. The PNI was the most suitable marker regardless of histological type. The SII and PNI were the most promising markers for patients with and without PD-L1 expression, respectively. [ABSTRACT FROM AUTHOR]

Background: Re-challenge of erlotinib after gefitinib failure is reported to yield some benefit in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation. However, little is known about the re-challenge of afatinib after 1st generate on EGFR tyrosine kinase inhibitor (TKI) failure.Methods: From May 2015 to August 2018, 62 patients with advanced NSCLC harboring sensitive EGFR mutation received afatinib after gefitinib and/or erlotinib failure at our institution was included in our retrospective study.Results: The overall response rate (ORR) and disease control rate (DCR) of afatinib as re-challenge were 17.0% and 79.2%, respectively. The median time on treatment of 1st generation EGFR-TKI (1st TKI) was 14 months. By multivariate analysis, smoking, performance status (PS), and time on treatment of 1st TKI with more than 10 months were confirmed to be independent prognostic factors predicting a worse progression-free survival (PFS), and significant prognostic markers for overall survival (OS) were PS and time on treatment of 1st TKI with more than 10 months, especially in patients with exon 19 deletion.Conclusions: Re-challenge of afatinib was identified as one of the therapeutic options after 1st TKI failure in the patients with advanced NSCLC harboring EGFR mutation when the time of treatment by prior 1st TKI is more than 10 months. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the chemotherapy response improves after exposure to immunotherapy. Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects that stimulate tumor shrinkage. We conducted a retrospective study to evaluate improvement of the efficacy of ramucirumab plus docetaxel after the failure of nivolumab as a PD‐1 inhibitor. Methods: From February 2016 to December 2017, 152 patients with non‐small cell lung cancer (NSCLC) administered nivolumab in our institution were identified. We reviewed the records of 20 NSCLC patients administered ramucirumab plus docetaxel after nivolumab failure. The overall response rate (ORR), progression‐free survival (PFS), and overall survival (OS) were investigated. Pegylated granulocyte colony‐stimulating factor was prophylactically administered to 18 patients (90%) after the administration of ramucirumab plus docetaxel. Results: The median age of the patients was 70 (range: 55–77) years. Twelve patients were male and eight were female. The histology was adenocarcinoma in 16 patients, squamous cell carcinoma in three, and other in one. The ORR of ramucirumab plus docetaxel was 60%, and the PFS and OS were 169 and 343 days, respectively. Among the 20 patients, 12 achieved a partial response, giving an ORR of 60.0%. Six patients had stable disease and two had progressive disease. The disease control rate was 90%. Gastrointestinal adverse events were frequently observed in 19 patients. Conclusions: Ramucirumab plus docetaxel achieved a higher response rate when administered immediately after nivolumab failure compared to regimens without prior nivolumab administration. [ABSTRACT FROM AUTHOR]

In the original publication of the article, the authors found few errors and the corrections are given below. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the effectiveness and tolerability of atezolizumab plus carboplatin and etoposide combination chemotherapy in elderly patients with extensive‐disease (ED) small‐cell lung cancer (SCLC). Methods: This retrospective study evaluated 65 SCLC patients who received atezolizumab, carboplatin, and etoposide for ED‐SCLC in nine study institutions between August 2019 and September 2020. Clinical efficacy, assessed according to response rate and survival, and toxicity were compared between the elderly (n = 36 patients; median age: 74 years [range: 70–89 years]) and the non‐elderly group (n = 29 patients; median age: 67 years [range: 43–69 years]). Results: The response rate was 73.8% (80.5% in the elderly group and 65.5% in the non‐elderly group). There was no significant difference in both the median progression‐free survival (5.5 months vs. 4.9 months, p = 0.18) and the median overall survival (15.4 months vs. 15.9 months, p = 0.24) between the elderly group and the non‐elderly group. The frequencies of grade ≥3 hematological adverse events in the elderly patients were as follows: decreased white blood cells, 36.1%; decreased neutrophil count, 61.1%; decreased platelet count, 8.3%; and febrile neutropenia, 8.3%. One treatment‐related death due to lung infection occurred in the elderly group. Conclusion: Despite hematologic toxicities, especially decreased neutrophil count, atezolizumab, carboplatin, and etoposide combination chemotherapy demonstrates favorable effectiveness and acceptable toxicity in elderly patients. Thus, atezolizumab plus carboplatin and etoposide could be the preferred standard treatment modality for elderly patients with ED‐SCLC. [ABSTRACT FROM AUTHOR]

Anti-programmed death-1 (PD-1) blockade is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, no appropriate modality exists for monitoring its therapeutic response immediately after initiation. Therefore, we aimed to elucidate the clinical relevance of 18F-FDG PET/CT versus CT in predicting the response to PD-1 blockade in the early phase. This prospective study included a total of 54 NSCLC patients. 18F-FDG PET/CT was performed at 4 weeks and 9 weeks after PD-1 blockade monotherapy. Maximum standardized uptake values (SULmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated. Among all patients, partial metabolic response and progressive metabolic disease after PD-1 blockade were observed in 35.2% and 11.1% on SULmax, 22.2% and 51.8% on MTV, and 27.8% and 46.3% on TLG, respectively, whereas a partial response (PR) and progressive disease (PD), respectively, based on RECIST v1.1 were recognized in 35.2% and 35.2%, respectively. The predictive probability of PR (MTV: 57.9% vs. 21.1%, p = 0.044; TLG: 63.2% vs. 21.1%, p = 0.020) and PD (MTV: 78.9% vs. 47.3%, p = 0.002; TLG: 73.7% vs. 21.1%, p = 0.007) detected based on RECIST at 4 weeks after PD-1 blockade initiation was significantly higher using MTV or TLG on 18F-FDG uptake than on CT. Multivariate analysis revealed that metabolic response by MTV or TLG at 4 weeks was an independent factor for response to PD-1 blockade treatment. Metabolic assessment by MTV or TLG was superior to morphological changes on CT for predicting the therapeutic response and survival at 4 weeks after PD-1 blockade. [ABSTRACT FROM AUTHOR]

• NSCLC diagnosis within 1 year of AID diagnosis increases risk of AID flares. • The safety profiles of combination immunotherapy monotherapy were comparable. • After inverse probability weighting, ICB versus without ICB prolonged survival. • These results support the use of ICB in patients with NSCLC and pre-existing AID. The risk and survival of patients with non-small cell lung cancer (NSCLC) with pre-existing autoimmune disorders (AIDs) receiving immune checkpoint blockade (ICB) therapy have not been clearly established. This multi-institutional, retrospective cohort study was conducted in collaboration with 20 centers in Japan. In total, 229 patients with advanced or recurrent NSCLC and pre-existing AID, with or without ICB treatment from January 2010–February 2020, were included and analyzed. Among 69 patients who received ICB, 2 received two lines of ICBs with a total of 71 ICB treatments; 57 (80.3 %) and 14 (19.7 %) patients received ICB monotherapy and combination therapy, respectively. AID flares were observed in 18 patients (25.4 %, 95 % confidence interval [CI], 15.8–37.1 %) receiving ICB. AID exacerbations were more likely when NSCLC was diagnosed less than 1 year after the AID diagnosis (odds ratio 5.26 [95 % CI, 1.40–21.61]; P = 0.016). Immune-related adverse events were observed in 32 patients (45.1 %, 95 % CI, 33.2–57.3 %); 17 had grade 3 or higher. The safety profile of combination immunotherapy was not significantly different from that of the monotherapy. After inverse probability weighting, the use of ICB prolonged survival (hazard ratio 0.43 [95 % CI, 0.26–0.70]; P = 0.0006). These findings revealed a novel risk factor for AID flares following ICB treatment, that is the diagnosis of NSCLC within 1 year of AID diagnosis, and showed that ICBs may improve survival in this population. These results support the utilization of ICB in patients with NSCLC and pre-existing AID. [ABSTRACT FROM AUTHOR]

Background: Biomarker assessments for nivolumab monotherapy efficacy in previously treated patients with non‐small cell lung cancer (NSCLC) remain unclear. We evaluated whether body mass index (BMI) and Glasgow prognostic score (GPS) are useful for assessing the efficacy of nivolumab alone as a second‐line treatment in patients with pretreated NSCLC. Methods: Data of 99 patients treated with second‐line nivolumab monotherapy for NSCLC between January 2016 and December 2019 were evaluated for prognostic values of BMI and GPS to assess their usefulness in predicting progression‐free survival (PFS) and overall survival (OS). Results: The Eastern Cooperative Oncology Group‐performance status (PS) independently predicted the second‐line nivolumab monotherapeutic effect; good PS (0–1) correlated with significantly longer PFS (4.3 vs. 1.9 months, log‐rank; p = 0.0004) and OS (17.7 vs. 4.6 months, log‐rank; p < 0.0001) than poor PS. BMI independently predicted survival, with high BMI (≥22.1 kg/m2) associated with significantly longer OS (19.1 vs. 8.5 months, log‐rank; p = 0.0023) than low BMI (<22.1 kg/m2). However, GPS showed no significant difference for PFS or OS. Conclusion: Among patients with NSCLC treated with nivolumab monotherapy as second‐line treatment, PS was significantly correlated with both PFS and OS and BMI with OS. Thus, BMI could be a useful predictor of survival in these patients. [ABSTRACT FROM AUTHOR]

Background: Osimertinib 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. Methods: Enrolled 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. Results: Thirty-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. Conclusion: Osimertinib 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. [ABSTRACT FROM AUTHOR]

Background: There are no established biomarkers for predicting the efficacy of first‐line pembrolizumab monotherapy in patients with high programmed death‐ligand 1 (PD‐L1) expression. In this study, we investigated whether the Glasgow prognostic score (GPS), neutrophil‐to‐lymphocyte ratio (NLR), and body mass index (BMI) can be used to evaluate the effect of first‐line pembrolizumab monotherapy in patients with advanced non‐small cell lung cancer (NSCLC) who express high levels of PD‐L1. Methods: We reviewed data from 142 patients with high PD‐L1 expression who underwent first‐line pembrolizumab monotherapy for NSCLC at six Japanese institutions between February 2017 and June 2019 and assessed the prognostic value of the GPS, NLR, and BMI. The Kaplan–Meier method and Cox proportional hazard models were used to examine differences in progression‐free survival (PFS) and overall survival (OS). The GPS, NLR, and BMI were calculated using C‐reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively. Results: The GPS independently predicted the first‐line pembrolizumab monotherapy efficacy, as a good GPS (GPS 0–1) was associated with a significantly better PFS and OS compared to a poor GPS (GPS 2) (PFS: 11.8 vs. 2.9 months, p < 0.0001; OS: not reached vs. 8.3 months, p < 0.0001). Furthermore, BMI independently predicted efficacy, as patients with high BMI (BMI ≥21.4) exhibited significantly better OS compared to those with low BMI (BMI <21.4) (OS: not reached vs. 14.1 months, p = 0.006). Conclusions: Among patients with high PD‐L1 expression undergoing first‐line pembrolizumab monotherapy for NSCLC, the GPS is significantly correlated with both PFS and OS, and BMI with OS, indicating that they could be used to predict treatment outcome in these patients. To the best of our knowledge, this is the first study to assess the relationship among the GPS, NLR, and BMI and survival among patients with high PD‐L1 expression undergoing first‐line pembrolizumab monotherapy for NSCLC. [ABSTRACT FROM AUTHOR]

Background: 2‐deoxy‐2‐[fluorine‐18] fluoro‐d‐glucose (18F‐FDG) positron emission tomography (18F‐FDG‐PET) is a convenient modality to assess the metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18F‐FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18F‐FDG uptake and programmed death ligands 1 and 2 (PD‐L1/PD‐L2) expression in patients with TETs. Methods: A total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18F‐FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD‐L1, PD‐L2, GLUT1, HIF‐1α, VEGFR2, VEGF‐C, and β2 adrenergic receptor. Results: High uptakes of SUVmax, SUVmean, MTV, and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%), and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS (performance status) of 1–2, thymic carcinoma, and advanced stage, and SUVmax on 18F‐FDG uptake displayed a close association with PD‐L1 and PD‐L2 expressions, but not with MTV and TLG. Our analysis revealed that SUVmax was identified as being significant relationship for positive PD‐L1/PD‐L2 expression. GLUT1, HIF‐1α, and VEGFR2 were significantly associated with the expression of PD‐L1/PD‐L2 from the biological viewpoint. Conclusion: 18F‐FDG accumulation was closely associated with the expression of PD‐L1/PD‐L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD‐L1/PD‐L2 could affect the glucose metabolism and hypoxia in thymic tumor cells. [ABSTRACT FROM AUTHOR]

Background: Among patients with non-small cell lung cancer (NSCLC), the impact of first-line treatment on overall survival (OS) may be influenced by subsequent therapies. Thus, using patient-level data, we assessed the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS among patients with high-programmed death-ligand 1 (PD-L1) expression undergoing first-line pembrolizumab monotherapy for NSCLC. Methods: We reviewed data from 133 patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC at 6 Japanese centers between February 2017 and December 2018. The correlations of PFS and PPS with OS were evaluated at the patient level. Results: Linear regression analyses and Spearman's rank correlation coefficient revealed that PPS was strongly correlated with OS (r = 0.76, p < 0.05, R2 = 0.65), while PFS was only moderately correlated with OS (r = 0.71, p < 0.05, and R2 = 0.4). Furthermore, PPS was significantly associated with performance status at the end of pembrolizumab monotherapy, as well as the use of platinum-based combination chemotherapy after pembrolizumab monotherapy (both p < 0.05). Conclusions: Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, PPS was more strongly correlated with OS, relative to the relationship between PFS and OS. Therefore, subsequent treatment appears to significantly influence OS in patients with disease progression following first-line pembrolizumab monotherapy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the relationship between tumor metabolic glycolysis and inflammatory or nutritional status in patients with advanced non-small cell lung cancer (NSCLC) who received programmed death-1 (PD-1) blockade. A total of 186 patients were registered in the present study. All of patients underwent 18F-FDG PET imaging before initial PD-1 blockade, and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed as indicators of 18F-FDG uptake. As inflammatory and nutritional index, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ration (PLR), systemic immune inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI) and Glasgow prognostic score (GPS) were evaluated based on previous assessment. 18F-FDG uptake by MTV and TLG significantly correlated with the scores of NLR, PLR, SII, PNI and ALI, in addition to the level of albumin, lactate dehydrogenase, C-reactive protein, white blood cells, neutrophils, lymphocytes and body mass index. The count of NLR, PLR and SII was significantly higher in patients with <1 year overall survival (OS) compared with in those with ≥1 year OS, and that of PNI and ALI was significantly lower in those with <1 year OS compared with those with ≥1 year OS. High MTV under the high PLR, SII and low ALI were identified as significant factors for predicting the decreased PFS and OS after PD-1 blockade in a first-line setting. In second or more lines, high MTV was identified as a significant prognostic predictor regardless of the levels of PLR, SII, ALI and GPS. In conclusion, metabolic tumor glycolysis determined by MTV was identified as a predictor for the outcome of PD-1 blockade under the high inflammatory and low nutritional conditions, in particular, when treated with a first-line PD-1 blockade. A high MTV under high PLR and SII and low ALI in the first-line setting could be more predictive of ICI treatment than other combinations. [ABSTRACT FROM AUTHOR]

Background: The effect of second‐line treatment on overall survival (OS) may be affected by subsequent treatment in patients with non‐small cell lung cancer (NSCLC); however, in such patients, the correlation between post‐progression survival (PPS) and OS is unclear. Our study assessed the correlation of progression‐free survival (PFS) and PPS with OS, using individual patient data, in advanced NSCLC patients who were treated with second‐line nivolumab monotherapy, Methods: Between January 2016 and March 2019, we evaluated 92 NSCLC patients who received second‐line nivolumab treatment after first‐line platinum‐based combination chemotherapy. Using individual patient data, the correlations of PFS and PPS with OS were examined. Results: Linear regression and Spearman rank correlation analysis demonstrated that PPS was strongly correlated with OS (r = 0.85, p < 0.05, R2 = 0.75), while PFS was moderately correlated with OS (r = 0.65, p < 0.05, R2 = 0.42). Performance status at the beginning of second‐line treatment, immune checkpoint inhibitor rechallenge, and the number of treatment regimens used post‐progression, after the second‐line treatment significantly correlated with PPS (p < 0.05). In advanced NSCLC patients who underwent second‐line treatment with nivolumab, in comparison to PFS, there was a stronger correlation between PPS and OS. Conclusions: Our findings suggest that subsequent treatment for disease progression after a second‐line nivolumab treatment had a significant impact on OS. [ABSTRACT FROM AUTHOR]

Background: There is currently insufficient information available on effective therapies that can be administered to patients with non‐small cell cancer (NSCLC) who develop resistance to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). However, sequential treatment via programmed death‐1 (PD‐1) blockade followed by EGFR‐TKI rechallenge is suggested to improve the therapeutic efficacy in such patients. Methods: A total of 75 patients with advanced NSCLC harboring sensitive EGFR mutations treated with afatinib, erlotinib, or gefitinib after EGFR‐TKI treatment failure were retrospectively analyzed. Among them, 13 patients were treated with EGFR‐TKI rechallenge immediately after the failure of PD‐1 blockade therapy (experimental group) and the remaining 62 patients did not receive PD‐1 inhibitor therapy before EGFR‐TKI rechallenge (control group). Blood samples were collected at two time points; before the initiation of anti‐PD‐1 therapy and at EGFR‐TKI rechallenge. Results: The objective response rates of EGFR‐TKI rechallenge in the experimental and control groups were 46.1% and 16.1%, respectively, with a significant difference (p = 0.026). In the experimental group, the median progression‐free survival (PFS) and overall survival (OS) after EGFR‐TKI rechallenge were 5.0 and 25.0 months, respectively, and no statistically significant difference in the percentage of lymphocytes before immune checkpoint inhibitor (ICI) therapy and EGFR‐TKIs was observed in patients with partial response (PR) and without PR after EGFR‐TKI rechallenge. In particular, the sequential treatment of PD‐1 blockade therapy followed by EGFR‐TKI rechallenge was consecutively repeated three times in two out of 13 patients in the experimental group, and EGFR‐TKI rechallenge consecutively for the third time yielded a PR without increased toxicities. Conclusions: EGFR‐TKI rechallenge immediately after PD‐1 blockade treatment was identified as an effective therapy for NSCLC patients with resistance to EGFR‐TKIs. [ABSTRACT FROM AUTHOR]

Background: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare tumor with an aggressive clinical course. However, there is limited knowledge of its treatment strategy. This retrospective study aimed to assess the efficacy and safety of anti-programed death-1 (PD-1) blockade monotherapy in previously treated advanced LCNEC. Methods: Eleven patients with previously treated advanced LCNEC who received immune checkpoint inhibitor monotherapy between January 2015 and November 2020 were retrospectively analyzed for efficacy and safety. Results: Of a total of 11 patients (median [range] age, 66 [37–79] years; 8 men [73%] and 3 women [27%]), 8 patients had performance status (PS) 0–1 [73%] and 3 patients had PS 2 [27%]; 9 patients received 1 prior chemotherapy [82%] and 2 patients received 2 prior chemotherapies [18%]. The median follow-up duration was 4.6 months. Although PD-1 blockade was administered at median cycles of 3 (range, 1–12), overall response rate, median progression-free survival, and median overall survival were 9.1%, 2.7 months, and 4.6 months, respectively. Any adverse events were observed in 9 patients (82%), including 1 patient with grade 3 pneumonitis as a serious adverse event. Conclusion: Anti-PD-1 blockade monotherapy as a subsequent line for previously treated advanced LCNEC exhibited usefulness and tolerability and was identified as a valid treatment option. [ABSTRACT FROM AUTHOR]

Background: The safety of pembrolizumab monotherapy in treatment‐naïve non‐small cell lung cancer (NSCLC) patients with high programed death‐ligand 1 (PD‐L1) expression and pre‐existing interstitial lung disease (ILD) has not yet been determined. Here, we aimed to evaluate the prognosis, efficacy and safety associated with pembrolizumab in such settings. Methods: In this single‐institution retrospective study conducted from May 2017 to October 2019, pembrolizumab was administered to 72 Japanese patients with treatment‐naïve advanced NSCLC with PD‐L1 tumor proportion score (TPS) ≥50%. Patients with ILD were assigned to the ILD group, and those without to the non‐ILD group. Between‐group comparisons were then performed. Results: Of the 72 patients, 61 (84.7%) were male. The median age was 70 years. A total of 64 patients (88.9%) had a smoking history, median PD‐L1 TPS status was 77.5%, and 10 of the 72 patients (13.9%) had ILD on pretreatment computed tomography. The objective response rate (ORR) was 45.8% and disease control rate (DCR) was 75.0%. The ORR was 70.0% and DCR was 90.0% in the ILD group, while the ORR was 41.9% and DCR was 72.6% in the non‐ILD group. The median overall survival was 568 days; the value in the non‐ILD group was 521 days, while in the ILD group was not reached. There was no significant difference between the two groups (log‐lank, P = 0.73). Conclusions: Pembrolizumab was administered to patients with pre‐existing ILD with no difference in prognosis compared to patients without ILD. In patients with ILD, physicians should consider the expected long‐term prognosis and risk of adverse events. [ABSTRACT FROM AUTHOR]

Background: Osimertinib is the most promising treatment option for patients with epidermal growth factor receptor (EGFR) mutation‐positive non‐small cell lung cancer (NSCLC) with acquired T790M resistance. However, recent studies have suggested that osimertinib could increase the frequency of serious adverse events (AEs) if administered immediately after immune checkpoint inhibitor (ICI) treatment. Methods: In this single‐institution retrospective study conducted from May 2016 to January 2019, osimertinib was administered to 47 patients with pretreated advanced NSCLC harboring the EGFR mutation. Results: Of the 47 patients, 20 (42.6%) were men and 27 (57.4%) were women. The median age was 71 years (range 37–83 years). A total of 19 patients (40.4%) had a smoking history. Furthermore, seven patients (14.9%) received osimertinib immediately after nivolumab therapy, while 40 patients (85.1%) were treated with osimertinib after treatment with drugs other than nivolumab. The frequency of grade 3 or 4 hepatotoxicity was significantly higher in patients with nivolumab prior to osimertinib (4/7; 57.1%) than in those treated with drugs other than nivolumab prior to osimertinib (2/40; 5.0%) (P = 0.0026). Liver biopsies were performed in two patients who received osimertinib immediately after nivolumab. In both patients, CD‐8‐positive T cell infiltration was predominantly observed in the liver tissues. Conclusions: The use of osimertinib immediately after nivolumab significantly increased the frequency of grade 3 or higher hepatotoxicity in patients with advanced NSCLC harboring EGFR mutation acquired T790M resistance. [ABSTRACT FROM AUTHOR]

Background: It remains unclear why radiation clinically provides a synergistic effect when combined with immune checkpoint inhibitors such as nivolumab. The purpose of our study was to retrospectively evaluate whether the therapeutic efficacy of nivolumab is improved as a result of a history of radiotherapy (RT) in patients with previously treated advanced non‐small cell lung cancer (NSCLC). Methods: From February 2016 to December 2017, 124 consecutive patients were administered nivolumab for pretreated advanced NSCLC. The patients were divided into RT and non‐RT groups. Results: Sixty‐six (53%) of the 124 patients had been administered RT before the initiation of nivolumab, 52 (42%) received extracranial RT, and 40 (32%) were treated with thoracic RT. The median number of nivolumab cycles was 4 (range: 1–43). The overall response rate (ORR) and disease control rate (DCR) of nivolumab in all patients were 28.0% and 58.4%, respectively. The ORR (36.4%) was significantly higher in patients who had received previous RT than in patients who had not received any RT (19%). The therapeutic efficacy of nivolumab was particularly noteworthy in patients with non‐adenocarcinoma and squamous cell carcinoma histology administered extracranial RT, with ORRs of 48.3% and 52.6%, and DCRs of 87.1% and 84.2%, respectively. Conclusion: Previous RT was an independent prognostic marker of favorable prognosis after nivolumab administration and improved the response rate to nivolumab treatment. Previous RT was clinically identified to have a synergistic effect with nivolumab treatment, increasing the response rate and improving the outcome of patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to retrospectively assess the incidence of interstitial lung disease (ILD) related to EGFR‐tyrosine kinase inhibitor (TKI) treatment immediately before and/or after the administration of a PD‐1 antibody. Methods: We analyzed the data of 26 patients who underwent treatment with EGFR‐TKIs immediately before and/or after the administration of an anti‐PD‐1 antibody. Results: Four out of the 26 patients developed ILD during EGFR‐TKI treatment: three patients during the administration of osimertinib immediately after, and one during afatinib immediately before treatment with an anti‐PD‐1 antibody. Three of 12 patients who underwent EGFR‐TKI therapy immediately after anti‐PD‐1 antibody treatment experienced osimertinib‐induced ILD. ILD was not observed in the five patients administered an anti‐PD‐1 antibody followed by first or second‐generation EGFR‐TKIs. Conclusion: ILD was observed in the treatment sequence of an anti‐PD‐1 antibody followed by osimertinib, but not with first or second‐generation EGFR‐TKIs. [ABSTRACT FROM AUTHOR]

A 70-year-old Japanese man was admitted to hospital because of decreased consciousness due to type II respiratory failure. Severe hypothyroidism was diagnosed and considered to be associated with hypoventilation due to respiratory muscle dysfunction and sleep apnea syndrome. His status was improved partially by replacement of thyroid hormone. Despite maintaining a euthyroid state, improvement of respiratory muscle dysfunction was incomplete. [ABSTRACT FROM AUTHOR]

To the best of our knowledge, no published reports have examined the significance of additional immune checkpoint inhibitors in treating malignancies, including lung cancer. Therefore, the present study aimed to examine the efficacy and feasibility of adding atezolizumab to carboplatin and etoposide combination chemotherapy for small cell lung cancer with extensive disease (ED-SCLC). The present retrospective analysis examined 16 patients with ED-SCLC who received the addition of atezolizumab to carboplatin and etoposide therapy during treatment at four institutions between August 2019 and September 2020. The effectiveness of treatment was evaluated based on tumor response, survival time and adverse events. Within the study cohort, there were 14 males (87.5%) and 2 females (12.5%), with a median age of 73.5 years (range, 62–79 years); 7 patients had a performance status (PS) of 0–1 (43.8%) and 9 had a PS of 2–3 (56.3%). The median follow-up period was 12.1 months. The overall response rate, median progression-free survival time and median overall survival time were 75.0%, 5.3 and 13.0 months, respectively. Regarding the frequency of hematological adverse events, the occurrence of grade ≥3 adverse events was observed, including decreased neutrophil (56.3%), white blood cell (50.0%) and platelet (43.8%) counts, as well as febrile neutropenia (12.5%). Although 1 patient developed grade 3 pneumonitis as a serious adverse event, no treatment-related deaths were observed. Despite the aforementioned hematological toxicities, the addition of atezolizumab to carboplatin and etoposide therapy during treatment demonstrated favorable efficacy and acceptable toxicity in ED-SCLC. Thus, adding atezolizumab to carboplatin and etoposide combination chemotherapy may be a treatment option for ED-SCLC. [ABSTRACT FROM AUTHOR]

Background Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of malignant pleural effusion (MPE). Here, a multicenter phase II trial to evaluate bevacizumab in non-squamous non-small cell lung carcinoma patients with MPE was conducted. Methods Patients having MPE with no prior treatment and performance status of 0–2 received carboplatin (area under the curve: AUC 6; up to 6 cycles) and pemetrexed (500 mg/m 2 ) with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was the control rate of MPE without pleurodesis at 8 weeks after treatment. VEGF levels in plasma and MPE were measured by enzyme immunoassay. Results Of 30 patients entered (median 66 years; 24 males; adenocarcinoma; 4 epidermal growth factor receptor: EGFR mutations), 28 patients (2 withdrawn patients) were given a median of 4 cycles of carboplatin, and 68% of the patients received maintenance pemetrexed with bevacizumab (median 8 cycles). At eight weeks, MPE was controlled without pleurodesis in 93% of treated patients (95% confidence interval: 77–99%). At the median follow-up time of 12.8 months, 78.6% of the cases required no pleurodesis. Response rate was 46%, and median progression-free survival (PFS) and overall survival (OS) were 8.2 months and 18.6 months, respectively. Toxicities of grade ≥3 included neutropenia (28.6%), thrombocytopenia (28.6%), proteinuria (3.6%), and hypertension (3.6%). Assessment of VEGF levels before treatment indicated that patients with low VEGF (<1000 pg/ml) in MPE frequently needed pleurodesis (p = 0.011), and that high VEGF (≥100 pg/ml) in plasma was indicative of poor prognosis in the context of PFS (p = 0.012). Conclusion The combination of bevacizumab with carboplatin and pemetrexed demonstrated efficacy with acceptable toxicities in patients with MPE. [ABSTRACT FROM AUTHOR]

Simple Summary: Thymic carcinoma is identified as thoracic neoplasm having low sensitivity to systemic chemotherapy. As first-line setting, platinum-based chemotherapy is administered, but, it is difficult to achieve long-term survival. Therefore, salvage chemotherapy is clinically considered as second or third line treatment. This study reviewed the therapeutic significance of several kinds of cytotoxic agents and molecular targeting drugs in patients with previously treated thymic carcinoma. The clinical trials of salvage chemotherapy in patients with thymic carcinoma are limited, and we cannot draw an optimal conclusion due to the small sample size. However, S-1, amrubicin, docetaxel, pemetrexed, and paclitaxel, sunitinib and lenvatinib yielded some efficacy to such patients. As S-1 and amrubicin are limited to Japan and East Asian, it remains unclear which regimens are better as second-line setting. Further investigation is warranted to establish the clinical evidence of salvage chemotherapy in advanced or metastatic thymic carcinoma by large-scale study. Thymic carcinoma is a rare neoplasm, and it is difficult to achieve complete remission with systemic chemotherapy. In advanced or recurrent thymic carcinoma, platinum-based chemotherapy is chosen as the first-line setting; however, it remains unclear which regimen is better to improve its outcome. It remains unknown whether salvage chemotherapy should be administered to patients with platinum-based chemotherapy-refractory thymic carcinoma. Currently, several clinical studies have investigated the efficacy of second-line settings for advanced thymic carcinoma. As cytotoxic agents, S-1, amrubicin, pemetrexed, docetaxel, paclitaxel, and gemcitabine have been reported as prospective phase II studies or retrospective studies. The overall response rates (ORRs) of S-1, amrubicin, and pemetrexed were 25–50%, 11–44.4%, and 9–10%, respectively. Molecular targeting drugs, such as sunitinib, everolimus, and lenvatinib, also provide clinical effectiveness with tolerability after the failure of platinum-based regimens. Based on the results of the prospective phase II study, the ORR, median progression-free survival, and median overall survival were 16.6% and 5.6 months, respectively, in everolimus, 26% and 7.2 months, respectively, in sunitinib, and 38% and 9.3 months, respectively, in lenvatinib. Although it is difficult to compare each study, lenvatinib appears to be better in increasing efficacy as a second-line setting. However, each study had a small sample size, which may have biased the results of their studies. Further investigation is warranted to elucidate the therapeutic significance of salvage chemotherapy in advanced thymic carcinoma in a large-scale study. [ABSTRACT FROM AUTHOR]

There is a lack of markers for predicting favorable outcomes after pembrolizumab therapy in patients with non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) expression ≥ 50%. This retrospective study examined the prognostic significance of 2-deoxy-2-[18F] fluoro-d-glucose (18F-FDG) uptake as a predictive marker of first-line pembrolizumab. Forty-eight patients with previously untreated NSCLC and PD-L1 expression levels ≥ 50% who underwent 18F-FDG-positron emission tomography (PET) just before administration of pembrolizumab monotherapy were eligible and underwent assessment of metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum of standardized uptake value (SUVmax) on 18F-FDG uptake. The objective response rate, median progression-free survival, and median overall survival were 51.1%, 7.1 months, and 18.6 months, respectively. In univariate survival analyses, high MTV was barely a significant prognostic predictor and was confirmed as an independent factor linked to worse outcomes in multivariate analysis, predominantly in patients with a histological diagnosis of adenocarcinoma. A high MTV was significantly associated with distant metastases (especially bone metastasis), C-reactive protein (CRP) level, and PD-L1 expression ≥ 75%. Metabolic tumor activity assessed as MTV from 18F-FDG uptake predicted the prognosis after first-line pembrolizumab treatment in patients with NSCLC and PD-L1 expression ≥ 50%, especially for adenocarcinoma. [ABSTRACT FROM AUTHOR]

It remains unclear whether the accumulation of 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) before the initiation of anti-programmed death-1 (PD-1) antibody can predict the outcome after its treatment. The aim of this study is to retrospectively examine the prognostic significance of 18F-FDG uptake as a predictive marker of anti-PD-1 antibody. Eighty-five patients with previously treated non-small cell lung cancer (NSCLC) who underwent 18F-FDG-positron emission tomography (PET) just before administration of nivolumab or pembrolizumab monotherapy were eligible in our study, and metabolic tumor volume (MTV), total lesion glycolysis (TLG) and the maximum of standardized under value (SUVmax) on 18F-FDG uptake were assessed. Objective response rate, median progression-free survival and median overall survival were 36.6%, 161 days and 716 days, respectively. The frequency of any immune-related adverse events was significantly higher in patients with low 18F-FDG uptake on PET than in those with high uptake. By multivariate analysis, the tumor metabolic activity by TLG and MTV was identified as an independent prognostic factor for predicting outcome after anti-PD-1 antibody therapy, but not SUVmax, predominantly in patients with adenocarcinoma. Metabolic tumor indices as TLG and MTV on 18F-FDG uptake could predict the prognosis after anti-PD-1 antibodies in patients with previously treated NSCLC. [ABSTRACT FROM AUTHOR]