A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, cisplatin-ineligible urothelial cancer.

BACKGROUND: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. RESULTS: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (≥median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (

Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial.

BACKGROUND: Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival benefit in melanoma with immune-related (ir) adverse events (irAEs) managed by the protocol-defined guidelines. This phase 2 study evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer (ED-SCLC). DESIGN: Patients (n=130) with chemotherapy-naïve ED-SCLC were randomized 1: 1: 1 to receive paclitaxel (175 mg/m2)/carboplatin (area under the curve=6) with either placebo (control) or ipilimumab 10 mg/kg in two alternative regimens, concurrent ipilimumab (ipilimumab+paclitaxel/carboplatin followed by placebo+paclitaxel/carboplatin) or phased ipilimumab (placebo+paclitaxel/carboplatin followed by ipilimumab+paclitaxel/carboplatin). Treatment was administered every 3 weeks for a maximum of 18 weeks (induction), followed by maintenance ipilimumab or placebo every 12 weeks. End points included progression-free survival (PFS), irPFS, best overall response rate (BORR); irBORR, overall survival (OS), and safety. RESULTS: Phased ipilimumab, but not concurrent ipilimumab, improved irPFS versus control [HR (hazard ratio)=0.64; P=0.03]. No improvement in PFS (HR=0.93; P=0.37) or OS (HR=0.75; P=0.13) occurred. Phased ipilimumab, concurrent ipilimumab and control, respectively, were associated with median irPFS of 6.4, 5.7 and 5.3 months; median PFS of 5.2, 3.9 and 5.2 months; median OS of 12.9, 9.1 and 9.9 months. Overall rates of grade 3/4 irAEs were 17, 21 and 9% for phased ipilimumab, concurrent ipilimumab and control, respectively. CONCLUSION: These results suggest further investigation of ipilimumab in ED-SCLC.

A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer.

BACKGROUND: This open-label phase III study assessed the addition of Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 to gemcitabine/cisplatin chemotherapy in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomized (1:1) to receive six or fewer 3-week cycles of i.v. gemcitabine (1250 mg/m2 on days 1 and 8) and cisplatin alone (75 mg/m2 on day 1, control arm) or combined with s.c. PF-3512676 0.2 mg/kg on days 8 and 15 of each chemotherapy cycle and weekly thereafter until progression or unacceptable toxicity (experimental arm). No crossover was planned. The primary end point was overall survival (OS). RESULTS: A total of 839 patients were randomized. Baseline demographics were well balanced. Median OS (11.0 versus 10.7 months; P=0.98) and median progression-free survival (PFS) (both 5.1 months) were similar between groups. Grade≥3 hematologic adverse events (AEs), injection-site reactions, and influenza-like symptoms were more frequently reported among patients receiving PF-3512676. At the first-interim analysis, the Data Safety Monitoring Committee recommended study discontinuation. Administration of PF-3512676 was halted based on efficacy futility and increased grade≥3 AEs (experimental arm). CONCLUSIONS: Addition of PF-3512676 to gemcitabine/cisplatin chemotherapy did not improve OS or PFS but did increase toxicity.

[Evaluation of treatment outcome for pulmonary tuberculosis with early introduction of intermittent methods, two years after the conclusion of treatment]. / Ocena wyników leczenia gruzlicy, pluc z wczesnym wprowadzeniem metody przerywanej, w dwa lata po zakonczeniu kuracji.

This publication is a continuation of our study for the treatment of pulmonary tuberculosis with early introduction of the intermittent methods. Early results were presented in a preliminary reports (Pneumonol. Alergol. Pol., 1995, 63, 57). From among 33 patients who were treated in this way, two-year follow-up was performed in 29 persons (we lost contact with two persons, 1 patient died from other reasons, and the next one was excluded for ambulatory prolongation of II phase of the treatment). 15 patients were supervised directly in our Department, and the others were estimated from records of Regional Antituberculosis Outpatient Clinics. Two years after the completion of therapy all 29 patients remained smear-negative and radiologically stable. On this basis, we assumed that results of the treatment of smear-positive pulmonary tuberculosis with early introduction of the intermittent methods are as good as standard therapy.

[Analysis of course and treatment results after treatment of pulmonary tuberculosis with early introduction of interrupted observation--preliminary report]. / Analiza przebiegu i wyników leczenia gruzlicy pluc z wczesnym wprowadzeniem kuracji nadzorowanej metoda przerywana--doniesienie wstepne.

The results of the treatment 33 patients for smear-positive pulmonary tuberculosis with Isoniazid, Rifampicin, Pyrazinamide and Streptomycin administrated during first two weeks daily, from 3 to 8 week also with these four drugs but in a little higher doses twice weekly and next Isoniazid and Rifampicin during 9-26 weeks also twice weekly as in standard Polish model were described. After therapy with above described regimen all patients became smear-negative and radiological improvement was observed. Drugs in higher doses were well tolerated. Only abnormality in laboratory findings was temporary elevated level of uric acid, which recovered to normal values before the end of therapy. Costs of antituberculous drugs were used in this regimen is approximately 35% lower than standard model in Poland.

[Spirometric investigation and spiro-ergometric test in evaluation of exercise tolerance in patients suffering from aluminosis and silicosis]. / Badanie spirometryczne a test spiroergometryczny w ocenie zdolnosci wysilkowej u chorych na pylice krzemowo-glinowa.

The main purpose of our research was to estimate the ventilation and physical efficiency in 6 patients suffering from aluminosis and silicosis. Chest X-ray examinations, statical spirometric investigations and spiroergometric tests (TSE) were performed. Oxygen levels achieved in this group were equal or even higher than medium values achieved by healthy people. Ability to physical effort can be estimated only using TSE.