Effect of polypharmacy on the outcomes of older patients with advanced non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors: A retrospective cohort study.

INTRODUCTION: The effect of polypharmacy on older patients with cancer is unclear. This study aimed to explore the effect of polypharmacy on the outcomes of treatment in older patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. MATERIALS AND METHODS: We retrospectively reviewed the records of older patients (aged ≥65 years) with advanced NSCLC who received PD-1/PD-L1 inhibitors with or without platinum-based chemotherapy as first-line treatment from March 2016 to December 2020. Patients with driver oncogenes or Eastern Cooperative Oncology Group performance status (PS) ≥2 were excluded. Polypharmacy was defined as receiving five or more oral or inhaled medications at baseline. We compared the progression-free survival (PFS), overall survival (OS), and mean cumulative length of hospital stays between the polypharmacy and non-polypharmacy groups. RESULTS: A total of 122 patients, with a median age of 72 years (range, 65-89 years), were included in the analysis. Of the patients, 34 (27.8%) had a PS of 0 and 68 (55.7%) had a PD-L1 tumor proportion score (TPS) of ≥50%. The median number of oral or inhaled medications was 4 (range, 0-12), and 60 (49.1%) patients were taking ≥5 medications (polypharmacy). Age and Charlson Comorbidity Index score were significantly higher in the polypharmacy group (P = 0.01 and P < 0.001, respectively). Compared with the non-polypharmacy group, the polypharmacy group had a similar median PFS (6.7 vs. 8.5 months, P = 0.94) and a shorter median OS (17.3 vs. 26.0 months, P = 0.04). In the polypharmacy group, the adjusted hazard ratio for OS (adjusted for age, PS, and PD-L1 TPS) was 1.65 (95% confidence interval, 1.04-2.86, P = 0.03). Patients in the polypharmacy group had longer hospital stays (46.3 ± 7.5 vs. 27.7 ± 4.1 days/person, P < 0.05) and more emergency hospitalizations (1.6 ± 0.3 vs. 0.8 ± 0.1 times/person, P < 0.05) during the first year. DISCUSSION: Polypharmacy was associated with shorter survival time and longer hospitalization in older patients with advanced NSCLC receiving first-line immunotherapy with or without chemotherapy.

The efficacy and safety of anamorelin among patients with diabetes.

BACKGROUND: Anamorelin is a selective ghrelin receptor agonist approved for cancer cachexia in Japan. Little is known about predictors of anamorelin efficacy. This study aimed to assess the effect of diabetes on the efficacy and safety of anamorelin in patients with cancer cachexia. METHODS: Medical records of patients with advanced non-small-cell lung, gastric, pancreatic, or colorectal cancer who received anamorelin between January 2021 and March 2023 were retrospectively reviewed. The diabetic (DM) group included patients with a confirmed diagnosis of type 2 diabetes mellitus, random plasma glucose of ≥ 200 mg/dL, or hemoglobin A1c of ≥ 6.5%. The maximum body weight gain and adverse events during anamorelin administration were compared between the DM and non-DM groups. Patients with a maximum body weight gain ≥ 0 kg were classified as the responders. RESULTS: Of 103 eligible patients, 31 (30.1%) were assigned to the DM group. The DM group gained less weight (median of -0.53% vs. + 3.00%, p < 0.01) and had fewer responders (45.2% vs. 81.9%, p < 0.01) than the non-DM group. The odds ratio for non-response in the DM group was 6.55 (95% confidential interval 2.37-18.06, p < 0.01), adjusted by age and performance status. The DM group had a higher cumulative incidence of hyperglycaemic adverse events (72.2% vs. 6.3%, p < 0.01) and more discontinuations due to hyperglycaemic adverse events (25.8% vs. 4.2%, p < 0.01) than the non-DM group. CONCLUSIONS: Patients with diabetes and cancer cachexia are less likely to gain weight with anamorelin despite a high risk of hyperglycaemic adverse events.

Concordance of ALK fusion gene-rearrangement between immunohistochemistry and next-generation sequencing.

BACKGROUND: Although various companion diagnostic tests of ALK fusion gene-rearrangement are approved, few reports have assessed the concordance of ALK fusion gene-rearrangement in two companion diagnostic tests: next-generation sequencing (NGS) testing and immunohistochemistry (IHC). METHODS: The samples evaluated for gene alterations using NGS testing between May 2019 and November 2021 were included in this study. The inclusion criteria were as follows: samples were diagnosed with non-small cell lung cancer; the results of the NGS analysis were informative; and samples had residual specimens for IHC. We performed IHC on the residual specimens and retrospectively collected sample characteristics from medical records. RESULTS: A total of 185 samples were analyzed using NGS. Twenty-six samples were excluded because of failure to analyze gene alterations using NGS, no residual samples, and inadequate IHC. We analyzed 159 samples. The major histological type was adenocarcinoma (115 samples). The number of surgical and transbronchial lung biopsy specimens was 59 and 56, respectively. ALK fusion gene-rearrangement was detected in four samples using NGS, and five were detected using IHC. The sensitivity and specificity of IHC referred to by NGS were 75.0% and 98.7%, respectively. The concordance rate between IHC and NGS was 98.1%. ALK rearrangement was detected in two patients using IHC but not using NGS. In addition, ALK rearrangement was detected in one patient using NGS but not using IHC. CONCLUSION: Our results suggest that IHC and NGS might be complementary tests. In patients suspected of harboring ALK fusion gene-rearrangement, it should be analyzed using another diagnostic method.

Relationship between patterns of immunohistochemical conventional neuroendocrine markers and efficacy of immune check point inhibitors in patients with extensive disease small cell lung cancer.

BACKGROUND: Which patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)-SCLC, to assess whether conventional NE markers are predictive of ICIs. METHODS: Patients with untreated ED-SCLC who received first-line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first-line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI-chemo group) and with chemotherapy alone (chemo group). RESULTS: A total of 227 patients were included in the ICI-chemo and chemo groups, respectively. The progression-free survival (PFS) tended to be better in patients in the ICI-chemo group than those treated with chemotherapy alone in patients with NE marker-positive SCLC. In particular, it was statistically significant in patients with chromogranin A-positive SCLC (p = 0.036). In patients with NE marker-negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker. CONCLUSION: Our study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker-negative SCLC.

Safety and efficacy of amrubicin with primary prophylactic pegfilgrastim as second-line chemotherapy in patients with small cell lung cancer.

BACKGROUND: Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P-PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P-PEG as second-line chemotherapy for SCLC. METHODS: We retrospectively reviewed patients with SCLC who received AMR as second-line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P-PEG in their regimen, patients (n = 60) were divided into P-PEG (n = 21) and non-P-PEG groups, and their clinical outcomes were evaluated. RESULTS: Median of AMR treatment cycles was five (range: 1-39 cycles) in P-PEG group and four (range: 1-15 cycles) in non-P-PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P-PEG group than in the non-P-PEG group. The objective response rates were 52.4% and 30.8%, and median progression-free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P-PEG and non-P-PEG groups, respectively. CONCLUSIONS: AMR with P-PEG as second-line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P-PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.

Chemotherapy for patients with advanced lung cancer with interstitial lung disease: a prospective observational study.

Introduction: Although recent advances in chemotherapy for lung cancer are remarkable, most clinical trials have excluded patients with interstitial lung disease (ILD) due to the concern of developing acute exacerbation (AE) of ILD. Hence, accumulating original evidence of cancer treatment for this population is important. Methods: Between 2016 and 2020, a prospective observational study was conducted across 11 Japanese hospitals. Patients with chemotherapy-naïve, inoperable, advanced lung cancer with ILD were included. The primary outcome was the frequency of AE-ILD after registration; the secondary outcomes were the risk factor of AE-ILD and the efficacy of chemotherapy. Results: Among 124 patients enrolled, 109 patients who received chemotherapy were analyzed. The median age was 72 years, and the majority showed usual interstitial pneumonia (UIP)/probable UIP pattern upon chest computed tomography. The median percent-predicted forced vital capacity (%FVC) was 81% (interquartile range: 66-95%). After registration, 23 patients (21.1%; 95% confidence interval [CI]: 14.4-29.7%) developed AE-ILD. The logistic analysis revealed that lower %FVC slightly but significantly increased the risk of AE-ILD (odds ratio per 10% decrease: 1.27; 95% CI: > 1.00-1.62). Overall response rates/median overall survival times in non-small-cell lung cancer and small-cell lung cancer for the first-line chemotherapy were 41% (95% CI: 31-53)/8.9 months (95% CI: 7.6-11.8) and 91% (95% CI: 76-98)/12.2 months (95% CI: 9.2-14.5), respectively. Conclusion: AE-ILD during chemotherapy is a frequent complication among patients with lung cancer with ILD, particularly those with lower %FVC. Conversely, even in this population, passable treatment response can be expected.

[A CASE OF REPEATED DRUG-INDUCED LUNG DISEASES DUE TO MULTIPLE HERBAL MEDICINES CONTAINING COMMON INGREDIENTS].

We present a rare case of repetitive lung disease caused by various herbal medicines containing common ingredients. In June 201X-2, an 81-year-old man with chronic sinusitis was treated with Shini-seihai-to. One month later, the patient experienced liver dysfunction, and pulmonary opacity was observed on a chest radiograph; this condition improved following the discontinuation of Shini-seihai-to. In October 201X-2, the patient developed fever and dyspnea after treatment with Saiko-keishi-to, which was administered to treat irritable bowel syndrome, and was diagnosed with pneumonia. His condition did not improve with antimicrobial treatment but did improve with systemic corticosteroids. Following discharge from the hospital, the patient took both Shini-seihai-to and Hochu-ekki-to. He developed a fever two days later, which improved after discontinuing the medicines. The patient developed a cough after taking Sairei-to in February 201X and was subsequently admitted to our hospital with respiratory failure; pulmonary opacity was observed on a chest computed tomography scan. On the basis of clinical course, lymphocytosis in bronchoalveolar lavage fluid, and drug-induced lymphocyte stimulation tests, we diagnosed the patient with Sairei-to-induced lung disease. The patient's condition improved after discontinuing Sairei-to. We conclude that common ingredients in different herbal medicines may cause drug-induced lung injury. Therefore, we recommend that scrupulous attention should be paid to Chinese herbal medicine use in patients with a history of lung injury induced by herbal medicines.