Feasibility, Tolerability, and Effectiveness of Transbronchial Interventions in Elderly Patients With Malignant Central Airway Obstruction: A Retrospective Single-institution Study.

BACKGROUND: In elderly patients with malignant central airway obstruction (MCAO), the treating physicians often hesitate to undertake transbronchial interventions (TBIs) as a palliative procedure in view of the advanced age of the patients. METHODS: We conducted this retrospective study to evaluate the differences in the feasibility, tolerability, and effectiveness of TBIs between elderly (aged 75 years old or above; elderly group; n=27) and nonelderly (aged below 75 years old; nonelderly group; n=50) patients with MCAO. The primary endpoint was the incidence of complications during (within 24 hours) and after (>24 hours) TBIs. RESULTS: The mean age of the patients was 81 years in the elderly group and 61 years in the nonelderly group. The complications encountered during/after TBI included endobronchial bleeding or hypoxemia requiring intubation occurring during the TBIs, and bacterial pneumonia, airway reocclusion, and stent migration occurring after the TBIs, although there was no difference in the frequency of complications during/after the TBIs between the elderly group and nonelderly group (26% vs. 30%, P =0.706). There was no difference in the percentage of patients in whom successful airway recanalization was achieved by TBI (93% vs. 80%, P =0.197), the percentage of patients who showed symptomatic improvement after the TBIs (67% vs. 76%, P =0.380) and the OS after the TBIs (6.1 vs. 7.3 months, P =0.704) between the 2 groups. CONCLUSION: TBIs can be undertaken without hesitation as a palliative procedure in elderly patients with MCAO.

Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small cell lung cancer in a real-world setting (OSI-FACT-EP).

OBJECTIVES: Osimertinib is the primary treatment for patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer. However, evidence of the outcomes of osimertinib treatment in patients over 75 years of age in the real-world setting is limited. MATERIALS AND METHODS: This retrospective study analyzed the data of 538 patients (203 elderly and 335 non-elderly) with EGFR mutation-positive lung cancer in whom osimertinib was initiated as first-line treatment between August 2018 and December 2019. Patients over 75 years of age were classified as elderly. The data cut-off date was February 28, 2022. RESULTS: The progression-free survival (PFS) did not significantly differ between the elderly and non-elderly groups [elderly group: median PFS, 16.9 months (95 % confidence interval (CI), 14.3-20.2); non-elderly group: median PFS, 22.1 months (95 % CI: 19.5-26.3); hazard ratio (HR) for the elderly against the non-elderly: 1.21 (95 % CI: 0.98-1.50), p = 0.079]. However, the time to treatment failure (TTF) was significantly shorter in the elderly than in the non-elderly [elderly group: median TTF, 14.0 months (95 % CI: 0.98-1.50); non-elderly group: median TTF, 21.8 months (95 % CI: 18.2-24.6); HR for the elderly against the non-elderly: 1.46 (95 % CI: 1.20-1.77), p < 0.001]. Furthermore, the rate of treatment discontinuation because of adverse events was 28.6 % in the elderly and 14.9 % in the non-elderly (p < 0.001). Among patients who discontinued treatment, the conversion rate to second-line treatment was 39.6 % in the elderly and 72.8 % in the non-elderly. In addition, the median overall survival was 30 months (95 % CI: 25.8-37.7) in the elderly and not reached (NR) (95 % CI: NR-NR) in the non-elderly (p < 0.001). CONCLUSION: In a real-world clinical setting, elderly patients receiving osimertinib as first-line treatment should be aware of the frequent inability to transition to second-line treatment due to adverse events.

Safety and efficacy of osimertinib rechallenge or continuation after pneumonitis: A multicentre retrospective cohort study.

INTRODUCTION: Although osimertinib is a standard first-line treatment for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, the incidence rate of pneumonitis associated with osimertinib is high. However, there are few reports about the safety and efficacy of osimertinib rechallenge after the development of pneumonitis. METHODS: We conducted a retrospective multicentre cohort study of consecutive patients who developed pneumonitis associated with osimertinib as a first-line and received osimertinib rechallenge. The primary outcome was the incidence rate of any grade pneumonitis after osimertinib rechallenge. The secondary outcome was treatment efficacy in patients after osimertinib rechallenge. RESULTS: In total, 33 patients who received osimertinib rechallenge were included. Of them, 26 patients had grade 1, 6 patients had grade 2, and 1 patient had grade 3 initial pneumonitis. The median follow-up period after the osimertinib rechallenge was 16.9 months (interquartile range, 11.1-21.3 months). After the start of osimertinib rechallenge, five patients (15%) experienced mild relapsed pneumonitis. Three of the five patients had similar imaging patterns for initial and relapsed pneumonitis. No significant differences in characteristics were observed between patients with and without relapsed pneumonitis. The median progression-free survival after osimertinib rechallenge was not achieved (95% confidence interval: 10.3 months - not reached). CONCLUSION: Osimertinib rechallenge was feasible and effective for patients who developed initial pneumonitis associated with first-line osimertinib therapy. Osimertinib might be considered a treatment option even after the development of mild initial pneumonitis.

Overall Survival of Small-cell Lung Cancer Patients With Malignant Central Airway Obstruction Who Received Chemotherapy Without Undergoing Transbronchial Interventions: A Single-institution Retrospective Study.

BACKGROUND/AIM: This study aimed to determine whether the prognosis of small-cell lung cancer (SCLC) patients with malignant central airway obstruction (MCAO) who receive chemotherapy without undergoing transbronchial intervention (TBI) is not inferior to that of SCLC patients without MCAO. PATIENTS AND METHODS: We compared overall survival (OS) from the time of SCLC diagnosis between stage III or IV SCLC patients with MCAO (MCAO group, n=22) and those without MCAO (non-MCAO group, n=88). MCAO is generally defined as >50% obstruction of the trachea or mainstem bronchi. RESULTS: The median interval from the time of SCLC diagnosis until the initiation of anticancer therapy and the median number of chemotherapy regimens were 6 days and 2 regimens, respectively, in the MCAO group and 15 days and 2 regimens in the non-MCAO group. During the median follow-up period of 11.7 months after SCLC diagnosis, 95% of the patients in the MCAO group and 85% of the patients in the non-MCAO group died. No difference in the median OS (11.9 months vs. 12.4 months, p=0.455) was seen between the MCAO group and the non-MCAO group. A multivariate analysis showed that the presence of MCAO was not associated with an increased risk of death in SCLC patients who received chemotherapy (p=0.664). CONCLUSION: The prognosis of SCLC patients with MCAO who receive chemotherapy without undergoing TBI is not inferior to that of SCLC patients without MCAO.

Prognosis of stage I non-small cell lung cancer patients aged ≥ 80 years who were considered medically operable but received best supportive care alone.

INTRODUCTION: Some elderly stage I non-small cell lung cancer (NSCLC) patients may refuse both stereotactic body radiotherapy (SBRT) and surgery and may instead desire best supportive care (BSC) alone, despite having a medically operable condition. METHODS: We retrospectively evaluated the differences in the 3-year overall survival (3-year OS) rates among elderly stage I NSCLC patients aged ≥ 80 years who received surgery (OP group, n = 39), SBRT (RT group, n = 32) or BSC alone (BSC group, n = 28), stratifying the later groups according to those who were medically inoperable (MI subgroup) and those who were considered medically operable but refused surgery (MO subgroup). RESULTS: During a median 39.1-month follow-up period, 44 patients died. The 3-year OS rates were longer and higher in the MI-RT subgroup and the OP group than in the MI-BSC subgroup (67%, 89%, and 22%, respectively; p = 0.001). No differences in the 3-year OS rates were seen among the MO-RT subgroup, the MO-BSC subgroup, and the OP group (75%, 70%, and 89%, respectively; p = 0.164). However, a multivariate analysis identified a performance status (PS) score of 1-2 or a Charlson comorbidity index (CCI) score of ≥2, as well as stage IB disease and BSC, as independently increasing the risk of death. CONCLUSIONS: Elderly stage I NSCLC patients who were medically operable but who refused surgery and desire BSC alone should be encouraged to undergo SBRT unless they have a good PS and are otherwise in healthy condition.

Drug-Related Pneumonitis Induced by Osimertinib as First-Line Treatment for Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Real-World Setting.

BACKGROUND: Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data currently are lacking. RESEARCH QUESTION: What is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest CT scans and clinical information during osimertinib exposure were collected until June 2020. The primary end point was DRP incidence identified through central review. RESULTS: A total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) had a diagnosis of DRP (all grades), and 21 patients (4.6%) had a diagnosis of grade 3 or more DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT scan patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and nonspecific interstitial pneumonia were found in 30, 21, 18, 9, and two patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio, 1.72; 95% CI, 1.01-2.89; P = .046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not affect treatment efficacy negatively. INTERPRETATION: For osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features.

Difference in the Overall Survival Between Malignant Central Airway Obstruction Patients Treated by Transbronchial Microwave Ablation and Stent Placement: A Single-institution Retrospective Study.

BACKGROUND/AIM: Transbronchial microwave ablation (MWA) can be performed safely in patients with malignant central airway obstruction (MCAO), under moderate sedation and a high fraction of inspired oxygen. PATIENTS AND METHODS: We retrospectively evaluated the difference in the overall survival (OS) after transbronchial interventions (TBIs) between MCAO patients with endoluminal or mixed-type obstruction who were treated by MWA (MWA group, n=34) and those with extraluminal obstruction who were treated by stent placement (STP) (STP group, n=27). RESULTS: The OS was longer in the MWA group than in the STP group (10.2 months vs. 4.5 months, p=0.001). A significant difference in the OS between the two groups was observed in the patients who received post-TBI anticancer therapy (27.2 months vs. 6.0 months, p=0.002). The OS tended to be longer in the MWA group than in the STP group, among the patients who received best supportive care alone (3.8 months vs. 1.8 months, p=0.068). Nine patients (26%) of the MWA group underwent additional MWA when tumor regrowth into the airway lumen was noted (median of TBI sessions, 3). Multivariate analysis identified the adoption of MWA as the initial treatment procedure to be independently associated with a reduced risk of death in patients with MCAO (hazard ratio=0.473, p=0.031). CONCLUSION: Adoption of MWA as the initial treatment procedure is beneficial in MCAO patients with endoluminal or mixed-type obstruction, regardless of whether patients receive post-TBI anticancer therapy or not.

Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT).

BACKGROUND: Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient. METHODS: We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS). RESULTS: The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2.82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P < 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), ≥50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%). CONCLUSION: During initial treatment with osimertinib, PD-L1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation.

Efficacy and safety of transbronchial microwave ablation therapy under moderate sedation in malignant central airway obstruction patients with respiratory failure: a single-institution retrospective study.

BACKGROUND: The safety and efficacy of transbronchial microwave ablation (TMA) therapy in patients with malignant central airway obstruction (CAO) with respiratory failure remains unclear. METHODS: A total of 38 patients with advanced non-small cell lung cancer (NSCLC) or lung metastases with malignant endoluminal obstruction received TMA therapy under moderate sedation and high fractions of inspired oxygen (FiO2). The success rate of airway patency restoration, complication rate, and overall survival time (OS) from the initiation of TMA therapy were compared in the following two groups of patients with malignant CAO patients: the group with respiratory failure (PaO2/FiO2 ≤ 300) (RF group, n = 10) and the group without respiratory failure (PaO2/FiO2 > 300) (non-RF group, n = 28) at the time of the TMA therapy. RESULTS: Both the RF group and non-RF group received a median of two sessions of TMA. There was no significant difference in the percentage of patients who showed restored airway patency after the first session of TMA (90% vs. 96%), in the complication rate of TMA therapy (10% vs. 11%), or in the OS (7.1 months vs. 9.1 months) between the RF group and the non-RF group. Multivariate analysis identified no significant association between TMA therapy and the risk of death in malignant CAO patients with respiratory failure (p = 0.196). CONCLUSION: TMA therapy under moderate sedation was well tolerated and effective in patients with malignant CAO, including those with respiratory failure.

Overall survival of super-elderly (85 years or older) advanced non-small cell lung cancer patients with active epidermal growth factor receptor mutations receiving first-line gefitinib therapy: a single-institute retrospective study.

BACKGROUND: The survival benefit of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy in super-elderly patients with advanced non-small cell lung cancer (NSCLC) harboring active EGFR mutations remains unclear. METHODS: We conducted a retrospective evaluation of the difference in the overall survival (OS) among super-elderly (aged ≥ 85 years) NSCLC patients who had received best supportive care alone (BSC group, n = 36), cytotoxic chemotherapy (CT group, n = 11) or EGFR-TKI therapy (TKI group, n = 22). RESULTS: The median age of the patients was 88 years. Among the 35 super-elderly NSCLC patients with an performance status (PS) score of 0-2, 11of 18 EGFR wild-type patients received cytotoxic chemotherapy and 15 of 17 EGFR-mutant patients received EGFR-TKI therapy with gefitinib (n = 13) or osimertinib (n = 2). The OS tended to be longer in the TKI group than in the CT or BSC group (16.9 months vs. 7.2 months or 9.8 months, p = 0.059). Among the 34 super-elderly NSCLC patients with a PS score of 3-4, 7 with EGFR-mutant received gefitinib therapy and the remaining 27 received BSC alone. The OS tended to be longer in the TKI group than in the BSC group (4.6 months vs. 2.3 months, p = 0.060). Multivariate analysis identified a good PS before the start of first-line therapy and presence of active EGFR mutations reduced a risk of death. CONCLUSIONS: Gefitinib appears to be useful as a salvage therapy in super-elderly NSCLC patients with active EGFR mutation, regardless of their PS.

Chemotherapy should be performed in epidermal growth factor receptor mutation-positive lung adenocarcinoma patients who had progressive disease to the first epidermal growth factor receptor-tyrosine kinase inhibitor.

After the failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, some non-small cell lung cancer patients desire to receive switching with another EGFR-TKI (TKI-switching), although cytotoxic chemotherapy has been recommended as second-line therapy. It is unclear who should not receive TKI-switching in these patients. We retrospectively evaluated overall survival (OS) from the initiation of first EGFR-TKI (first-TKI) therapy in advanced lung adenocarcinoma patients with active EGFR mutations (deletion of exon 19 or L858R in exon 21) who received TKI-switching according to the best response of the first-TKI. There was no difference in the OS between patients receiving TKI-switching (n = 35) and patients receiving additional chemotherapy between the first-TKI and second-TKI therapy (n =10) (P = 0.614). Among patients receiving TKI-switching, the OS in cases with progressive disease to the first-TKI (n = 9) was shorter than that in cases with disease control to the first-TKI (n = 26) (12.7 months vs. 49.4 months, P < 0.001). Five of the nine progressive disease cases who received TKI-switching missed an opportunity to receive chemotherapy. Their OS tended to be shorter than that in patients who received chemotherapy during the whole period of anticancer therapy (12.2 months vs. 20.3 months, P = 0.060). The multivariate analysis showed that disease control to the first-TKI therapy (P = 0.005) or the presence of chemotherapy (P = 0.087) decreased the risk of mortality. Chemotherapy should be performed in patients with progressive disease to the first-TKI.

Timing of resumption of immune checkpoint inhibitor therapy after successful control of immune-related adverse events in seven advanced non-small cell lung cancer patients.

Among advanced non-small cell lung cancer (NSCLC) patients in whom grade 2/3 immune-related adverse events (irAEs) that had developed during the initial immune checkpoint inhibitor (ICI) therapy had been successfully controlled, we experienced three patients in whom ICI therapy was resumed at the diagnosis of progressive disease (PD group, n = 3) and four patients in whom it was resumed immediately after successful control of irAEs (non-PD group, n = 4). The tumor response rate, disease control rate to the resumed ICI and progression-free survival from the resumption of ICI therapy were 0%, 0% and 2 months in the PD group and 25%, 75% and 4.8 months in the non-PD group. In advanced NSCLC patients in whom resumption of discontinued ICI therapy was planned, the ICI therapy should be resumed immediately after successful control of irAEs, rather than at the diagnosis of PD.

Survival Analysis for Patients with ALK Rearrangement-Positive Non-Small Cell Lung Cancer and a Poor Performance Status Treated with Alectinib: Updated Results of Lung Oncology Group in Kyushu 1401.

LESSONS LEARNED: Alectinib confers a pronounced survival benefit in patients with ALK rearrangement-positive non-small cell lung cancer and a poor performance status. Survival benefit of alectinib for patients with a poor performance status was consistent regardless of the presence of central nervous system metastases. BACKGROUND: We previously reported a marked objective response rate (ORR) and safety for alectinib treatment in patients with ALK rearrangement-positive non-small cell lung cancer (NSCLC) and a poor performance status (PS) in the Lung Oncology Group in Kyushu (LOGiK) 1401 study. It remained unclear, however, whether alectinib might also confer a long-term survival benefit in such patients. METHODS: Eighteen patients with ALK rearrangement-positive advanced NSCLC and a PS of 2, 3, or 4 (n = 12, 5, and 1, respectively) were enrolled in LOGiK1401 between September 2014 and December 2015 and received alectinib. We have now updated the survival data for the study. RESULTS: The median follow-up time for all patients was 27.3 months. The median progression-free survival (PFS) was 16.2 months (95% confidence interval [CI], 7.1-30.8 months), and the median survival time (MST) and the 3-year overall survival rate were 30.3 months (95% CI, 11.5 months to not reached) and 43.8% (95% CI, 20.8-64.7%), respectively. This survival benefit was similarly manifest in patients with a PS of 2 (MST, 20.5 months) and those with a PS of ≥3 (MST, not reached). PFS did not differ between patients with or without central nervous system (CNS) metastases at baseline (median of 17.5 and 16.2 months, respectively, p = .886). CONCLUSION: Alectinib showed a pronounced survival benefit for patients with ALK rearrangement-positive NSCLC and a poor PS regardless of the presence of CNS metastases, a patient population for which chemotherapy is not indicated.

Prognosis of EGFR-mutant Lung Adenocarcinoma Patients With Malignant Pleural Effusion Receiving First-line EGFR-TKI Therapy Without Pleurodesis: A Single-institute Retrospective Study.

BACKGROUND/AIM: The survival benefit of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy without pleurodesis in EGFR-mutant lung adenocarcinoma patients with malignant pleural effusions (MPE) remains unclear. PATIENTS AND METHODS: We retrospectively evaluated overall survival (OS) among EGFR wild-type lung adenocarcinoma patients with MPE who received chemotherapy with pleurodesis (CT+PLD) and without pleurodesis (CT-PLD), and EGFR-mutant lung adenocarcinoma patients with MPE who received EGFR-TKI therapy with pleurodesis (TKI+PLD) and without pleurodesis (TKI-PLD). RESULTS: There was no difference in OS between the CT+PLD and the CT-PLD groups (10.8 months vs. 7.4 months). As compared to the TKI+PLD group, OS tended to be longer in the TKI-PLD group (21.8 months vs. 31.1 months). Patients in the TKI-PLD group had no hypoalbuminemia or deterioration of performance status during management of MPE and could receive second- and further-line therapy. CONCLUSION: EGFR-mutant patients with MPE who received first-line EGFR-TKI therapy without pleurodesis may show a better prognosis than those with pleurodesis.

Additional bevacizumab in EGFR-mutant lung adenocarcinoma patients who had oligo-progression after the failure of EGFR-TKI: A single-institute retrospective study.

INTRODUCTION: In EGFR-mutant NSCLC patients with oligo-progression disease (oligo-PD) after the EGFR-TKI failure, additional local ablative therapy (LAT) including stereotactic ablative radiotherapy reportedly extends the duration of the current EGFR-TKI and prolongs survival times. In clinical practice, however, all the patients cannot receive LAT for oligo-PD. METHODS: We retrospectively evaluated the efficacy and tolerability of additional bevacizumab as an alternative to LAT for oligo-PD after the EGFR-TKI failure in previously treated lung adenocarcinoma patients (median number of previous therapies, 2 regimens). Oligo-PD was defined as a situation in which disease progression has occurred in less than 5 anatomical sites after EGFR-TKI that has achieved at least stable disease. RESULTS: During a median 29.6-month follow-up period from the initiation of EGFR-TKI, 9 patients developed oligo-PD. One patient underwent LAT, but other 8 patients did not because of a few micro-metastatic lesions (n = 2), meningitis (n = 1), no indication of pleurodesis (n = 1), patient refusal (n = 2) or oligo-PD in the LAT treated sites (n = 3). Additional bevacizumab with continuation of the current EGFR-TKI had a disease control rate of 100% and a median time of progression-free survival from additional bevacizumab until another PD was 8.8 months. The reason for the discontinuation was because of another PD (n = 6) or treatment-related adverse events (n = 3). Four patients received sequential therapy and overall survival from additional bevacizumab was 10.1 months. CONCLUSIONS: Additional bevacizumab could be useful for EGFR-mutant adenocarcinoma patients with oligo-PD after the EGFR-TKI failure.

Toxicity and Efficacy of Sequential Chemotherapy in Patients with p-stage I Non-small Cell Lung Cancer that Recurring during Postoperative Tegafur-Uracil Adjuvant Chemotherapy.

It is not clear whether sequential chemotherapy can be performed immediately in patients with p-stage I non-small cell lung cancer recurring during a 2-year period of daily oral administration with tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. Patients receiving chemotherapy within 1 month after the discontinuation of UFT (n = 10) (five cases with aggressive recurrent tumors) had the increased risk of grade 4 neutropenia, but the overall survival was not inferior to that in patients who received chemotherapy beginning more than 1 month (n = 11). We could perform sequential chemotherapy immediately while paying attention to grade 4 neutropenia.

Re-administration of Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer Who Recovered from Chemotherapy-induced Interstitial Lung Disease.

We reported that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor re-administration (TKI-R) might be salvage therapy in patients with advanced non-small cell lung cancer after recovery from EGFR-TKI-induced interstitial lung disease (ILD). Here we retrospectively evaluated whether chemotherapy re-administration (CT-R) was effective in patients after chemotherapy-induced ILD. After providing their informed consent due to the risk of severe ILD, five patients received CT-R and six received TKI-R with oral administration of 0.5 mg/kg prednisolone. The overall survival (OS) from the occurrence of drug-induced ILD was shorter in CT-R cases than that in TKI-R cases (7.3 months vs. 25.4 months, p=0.003). The median duration of OS, however, was 7.3 months in cases with CT-R and 1.9 months in cases without CT-R. Multivariate analysis showed that CT-R as well as TKI-R tended to reduce the risk of mortality. CT-R might be salvage therapy in such patients, although the benefit of CT-R was smaller than that of TKI-R.

Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease.

PURPOSE: Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome. METHODS: We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not. RESULTS: EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone. CONCLUSIONS: EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.

Alectinib for Patients with ALK Rearrangement-Positive Non-Small Cell Lung Cancer and a Poor Performance Status (Lung Oncology Group in Kyushu 1401).

INTRODUCTION: Alectinib has shown marked efficacy and safety in patients with anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangement-positive NSCLC and a good performance status (PS). It has remained unclear whether alectinib might also be beneficial for such patients with a poor PS. METHODS: Eligible patients with advanced ALK rearrangement-positive NSCLC and a PS of 2 to 4 received alectinib orally at 300 mg twice daily. The primary end point of the study was objective response rate (ORR), and the most informative secondary end point was rate of PS improvement. RESULTS: Between September 2014 and December 2015, 18 patients were enrolled in this phase II study. Of those patients, 12, five, and one had a PS of 2, 3, or 4, respectively, whereas four patients had received prior crizotinib treatment. The ORR was 72.2% (90% confidence interval: 52.9-85.8%). The ORR did not differ significantly between patients with a PS of 2 and those with a PS of 3 or higher (58.3% and 100%, respectively [p = 0.114]). The PS improvement rate was 83.3% (90% confidence interval: 64.8-93.1%, p < 0.0001), with the frequency of improvement to a PS of 0 or 1 being 72.2%. The median progression-free survival was 10.1 months. Toxicity was mild, with the frequency of adverse events of grade 3 or higher being low. Neither dose reduction nor withdrawal of alectinib because of toxicity was necessary. CONCLUSIONS: Alectinib is a treatment option for patients with ALK rearrangement-positive NSCLC and a poor PS.