Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients

Background: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need. Patients and methods: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry. Results: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months). Conclusion: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic

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Correction to: Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients.

Clinical and Translational Oncology.

Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients.

BACKGROUND: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need. PATIENTS AND METHODS: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry. RESULTS: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months). CONCLUSION: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic.

Nonbacterial thrombotic endocarditis associated with lung adenocarcinoma.

Nonbacterial thrombotic endocarditis (NBTE) is a rather frequent neoplasic complication, most often occurring in adenocarcinomas of the lung and pancreas. The most frequent clinical manifestation is one of multiple cerebral infarcts, but other ischaemic events can occur. Diagnosis is frequently missed on transthoracic ultrasound, making transoesophagic ultrasound a more reliable diagnostic tool. We present a case of NBTE associated with lung adenocarcinoma.

Nonbacterial thrombotic endocarditis associated with lung adenocarcinoma

Nonbacterial thrombotic endocarditis (NBTE) is a rather frequent neoplasic complication, most often occurring in adenocarcinomas of the lung and pancreas. The most frequent clinical manifestation is one of multiple cerebral infarcts, but other ischaemic events can occur. Diagnosis is frequently missed on transthoracic ultrasound, making transoesophagic ultrasound a more reliable diagnostic tool. We present a case of NBTE associated with lung adenocarcinoma (AU)

Flegmasia cerulea dolens en paciente con carcinoma testicular / Phlegmasia cerulea dolens in patients with testicular carcinoma

Describimos un caso de flegmasia cerulea dolens secundaria a una trombosis venosa profunda por compresión de la vena cava inferior, en un varón de 31 años con un tumor germinal. Necesitó un tratamiento urgente con agentes fibrinolíticos, heparina intravenosa y quimioterapia. Con el tratamiento obtuvo una respuesta completa tumoral y una completa revascularización de la vena cava y vena femoral derecha

We describe a case of phlegmasia cerulea dolens secondary to venous thrombosis due to compression of inferior vena cava, in a 31-year-old man with a germ cell tumour. He was treated with systemic thrombolytic agents, intravenous heparin and urgent chemotherapy He presented a complete tumoral response and complete revascularization of the vena cava and right femoral vein

[Phlegmasia cerulea dolens in patients with testicular carcinoma]. / Flegmasia cerulea dolens en paciente con carcinoma testicular.

We describe a case of phlegmasia cerulea dolens secondary to venous thrombosis due to compression of inferior vena cava, in a 31-year-old man with a germ cell tumour. He was treated with systemic thrombolytic agents, intravenous heparin and urgent chemotherapy He presented a complete tumoral response and complete revascularization of the vena cava and right femoral vein.