Prospective Observational Study of Ramucirumab Plus Docetaxel After Combined Chemoimmunotherapy in Patients With Non-Small-Cell Lung Cancer.

BACKGROUND: A history of pre-administration of immune checkpoint inhibitors has been reported to be associated with good outcomes of ramucirumab (RAM) plus docetaxel (DOC) combination therapy for advanced non-small-cell lung cancer (NSCLC). However, existing knowledge on the clinical significance of RAM and DOC following combined chemoimmunotherapy is limited. Therefore, we evaluated the efficacy and safety of RAM plus DOC therapy after combined chemoimmunotherapy and attempted to identify the predictors of its outcomes. PATIENTS AND METHODS: This multicenter, prospective study investigated the efficacy and safety of RAM plus DOC after combined chemoimmunotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. An exploratory analysis measured serum cytokine levels at the start of treatment. RESULTS: Overall, 44 patients were enrolled from 10 Japanese institutions between April 2020 and June 2022. The median PFS and OS were 6.3 and 22.6 months, respectively. Furthermore, the ORR and DCR were 36.4% and 72.7%, respectively. The high vascular endothelial growth factor D (VEGF-D) group had a significantly shorter PFS and OS. A combination of high VEGF-A and low VEGF-D levels was associated with a longer PFS. CONCLUSION: Our results showed that RAM plus DOC after combined chemoimmunotherapy might be an effective and relatively feasible second-line treatment for patients with advanced NSCLC in a real-world setting.

Optimal Inhalation Profile of Pressurized Metered Dry Powder Inhaler Using a Valved Holding Chamber: A Dynamic Analysis.

Background: The combined use of a pressurized metered-dose inhaler and valved holding chamber (pMDI+VHC) is recommended to improve efficiency and safety; however, aerosol release is likely to vary with the inhalation maneuver. This in vitro study investigated the aerodynamic characteristics and aerosol release features of pMDI+VHC (Aerochamber, Trudell Medical International). Methods: The static and dynamic changes in the airway resistance (Raw) during inhalation (withdrawal) through pMDI+VHC were measured. Subsequently, the aerosol released from pMDI+VHC was measured using simplified laser photometry during withdrawal with either fast ramp-up then steady or slow ramp-up followed by gradual decrement at different intensities and times to peak flow (TPWF). Results: Raw increased linearly with changes in the withdrawal flow (WF) rate between 10 and 50 L/min. The slope was steep in the low WF range (<50 L/min) and became milder in the higher range. The aerosol mass tended to increase with an increase in the peak WF (PWF) of slow ramp-up profile. When three different WF increment slopes (TPWF: 0.4, 1.4, and 2.4 seconds) were compared, the released aerosol mass tended to decrease, and the aerosol release time was prolonged at longer TPWF. When the PWF was increased, the aerosol release time became shorter, and the withdrawn volume required for 95% aerosol release became larger; however, it did not exceed 0.4 L at suitable TPWF (0.4 seconds). Conclusion: Raw analysis suggests that inhalation at 30-50 L/min is suitable for pMDI+VHC in this setting. Rapid (TPWF, 0.4 seconds) inhalation, but not necessarily long (maximum 2.0 seconds) and deep (but larger than 0.55 L), is also recommended. Practically, direct inhalation to be weaker than usual breathing, as fast as possible, and far less than 2.0 seconds.

Perioperative Evaluation of the Physical Quality of Life of Patients with Non-Small Cell Lung Cancer: A Prospective Study.

Surgery is the most effective treatment for early-stage lung cancer; however, it poses a higher physical burden than other treatment options. Therefore, understanding the perioperative course of patients is important. Using the Short Form Health Survey 36, we prospectively measured the physical quality of life of patients who underwent anatomical pulmonary resection for non-small cell lung cancer at Shonan Kamakura General Hospital, Kanagawa, Japan (n = 87). In the preoperative setting, patients who had lower performance status and lived alone had significantly worse physical quality of life scores on multivariate analysis (regression coefficient (95% confidence interval), -9.37 (-13.43--5.32) and -10.22 (-13.74--7.40), respectively, p < 0.0001 for both). At 6 months postoperatively, patients who stopped smoking within 1 year preoperatively (stopped smoking within 1 year vs. remote or never smokers, 41.0 ± 10.5 vs. 48.6 ± 7.2, p = 0.002), had lower performance status (0 vs. 1-2, 49.3 ± 6.6 vs. 38.6 ± 9.6, p < 0.0001), lived alone (living alone vs. living with somebody, 41.6 ± 9.7 vs. 48.1 ± 7.9, p = 0.021), and had higher comorbid burden (Charlson comorbidity index <3 vs. ≥3, 48.2 ± 6.9 vs. 39.1 ± 14.7, p = 0.003) had significantly worse physical quality of life scores on univariate analysis. More recent smoking (regression coefficient (95% confidence interval), -4.90 (-8.78-1.0), p = 0.014), lower performance status (8.90 (5.10-12.70), p < 0.0001), living alone (5.76 (1.39-10.13), p = 0.01), and higher comorbid burden (-6.94 (-11.78--2.10), p = 0.006) were significant independent predictors of worse postoperative physical quality of life on multivariate analysis. Therefore, patients with these conditions might need additional support to maintain their physical condition after anatomical lung cancer surgery.

Prognostic impact of concomitant pH-regulating drugs in patients with non-small cell lung cancer receiving epidermal growth factor receptor tyrosine kinase inhibitors: the Tokushukai REAl-world Data project 01-S1.

PURPOSE: This study aimed to examine the prognostic impact of concomitant pH-regulating drug use in patients with epidermal growth factor receptor (EGFR)-mutation-positive non-small-cell lung cancer (NSCLC) receiving EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We conducted a nationwide retrospective cohort study and reviewed clinical data of consecutive patients with NSCLC treated with the first-line EGFR-TKIs in 46 hospitals between April 2010 and March 2020. Cox regression analyses were conducted to examine the differences in overall survival (OS) between patients treated with and without concomitant pH-regulating drugs, including potassium-competitive acid blockers (P-CABs), proton pump inhibitors (PPIs), and H2-receptor antagonists (H2RAs). RESULTS: A total of 758 patients were included in the final dataset, of which 307 (40%) were administered concomitant pH-regulating drugs while receiving frontline EGFR-TKIs. After adjusting for basic patient characteristics, patients administered gefitinib, erlotinib, afatinib, and osimertinib with concomitant pH-regulating drugs had lower OS than those without concomitant pH-regulating drugs, with hazard ratios of 1.74 (with a 95% confidence interval of 1.34-2.27), 1.33 (0.80-2.22), 1.73 (0.89-3.36), and 5.04 (1.38-18.44), respectively. The 2-year OS rates of patients receiving gefitinib with or without concomitant pH-regulating drugs were 65.4 and 77.5%, those for erlotinib were 55.8 and 66.6%, and those for afatinib were 63.2 and 76.9%, respectively. The 1-year OS rates of patients receiving osimertinib with or without concomitant pH-regulating drugs were 88.1% and 96.9%, respectively. CONCLUSION: In addition to the first-generation EGFR-TKIs, the second- and third-generation EGFR-TKIs also resulted in OS deterioration in patients with EGFR mutation-positive NSCLC when used concurrently with pH-regulating drugs.