•The COVID-19 pandemic has reshaped health-care systems worldwide.•Roughly 20% of patients develop complications and 3–6% die from COVID-19.•Patients with malignancy are more susceptible to severe ...infection and mortality from COVID-19.•Metastatic lung cancer and haematological cancer patients appear to be at greatest risk of severe complications and mortality from COVID-19.•There may be biological overlap between the inflammation caused by immune-related pneumonitis, chimeric antigen receptor T-cell cytokine release syndrome and COVID-19 pneumonitis.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and its clinical manifestation, the coronavirus disease 2019 (COVID19) have rapidly spread across the globe, leading to the declaration of a pandemic. While most present mild symptoms, it appears as though nearly 20% of confirmed patients develop significant complications. These include acute respiratory distress syndrome, septic shock and multi-organ failure, with a 3–6% mortality. A plethora of treatments has been or is being assessed, but to date, none has been proven effective. Management is mainly symptomatic, with organ support for the critically ill. Several reports, mainly case series, from across the world have concluded that patients with malignancy appear more susceptible to severe infection and mortality from COVID-19. This could be attributed to immunosuppression, co-existing medical conditions and underlying pulmonary compromise which is often the case in lung malignancy. Patients with haematological cancer and those who are receiving active chemotherapy treatment may be at greatest risk due to increased immunosuppression. This pandemic tested the resilience of worldwide health-care systems in an unprecedented manner. It has forced oncologists to rethink the entire diagnostic and therapeutic process, based on the local prevalence and impact of COVID-19. In this review we will discuss the impact of COVID-19 on patients affected by cancer, their diagnosis and management, as well as the pathophysiology of COVID-19 induced acute respiratory distress symptoms and currently investigated treatment approaches.
Introduction
The efficacy of immune checkpoint inhibitors in patients with brain metastases (BMs) from non-oncogene addicted non-small cell lung cancer (NSCLC) is under investigation. Here, we sought ...to determine the optimal management of NSCLCs with PD-L1 ≥ 50% and asymptomatic BMs who were treated with first-line pembrolizumab.
Methods
Thirty patients from 15 institutions with PD-L1 ≥ 50% NSCLC had asymptomatic BMs, and met inclusion criteria. Patients were classified based on whether they had undergone upfront local radiotherapy for BMs as well as on the type of brain radiotherapy received.
Results
Nine patients were treated with upfront pembrolizumab alone, 8 patients with whole-brain radiotherapy (WBRT) followed by pembrolizumab and 13 patients with stereotactic radiosurgery (SRS) followed by pembrolizumab. Patients’ characteristics were similar among the three groups of patients except for a higher number of BMs ≥ 3 in the WBRT group. One complete and 4 partial intracranial responses were observed with upfront pembrolizumab alone. The median survival was not reached for the pembrolizumab and WBRT (
n
= 8) groups, and it was 7.6 months for the SRS (
n
= 13) group (
P
= 0.09), with 12-month survival rates being 55.5%, 62.5%, and 23.0%, respectively. Salvage WBRT was delivered in 1 patient in the upfront pembrolizumab group and in 4 patients in the SRS group.
Conclusions
Upfront pembrolizumab showed efficacy in selected patients with PD-L1 ≥ 50% non-oncogene addicted NSCLC and asymptomatic BMs. Prospective studies should address whether pembrolizumab alone, and deferral of radiotherapy, could be pursued in this patient population.
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for patients with EGFR mutated non-small cell lung cancer as first-line treatment. ...However, treatment resistance inevitably emerges and may present as oligo-progressive disease (OPD) or systemic progressive disease (SPD). The incidence of OPD on first-line osimertinib is unknown.
We retrospectively analyzed patients who received first-line osimertinib at 13 Swiss centers. The rate of OPD (PD in ≤ 5 lesions) and treatment outcomes were analyzed.
The median age of the 148 patients was 68.2 years (range. 38.0-93.3). There were 62 % females, 83 % with a PS ≤ 1, 59 % never smokers, 57 % of patients with an EGFR exon 19 deletion and 37 % with EGFR p.L858R exon 21. 77 % experienced OPD. Median overall survival (OS) was 51.6 months (95 % CI, 38.4-65.0). Median progression-free survival (PFS) was 19.2 (95 % CI, 14.3-23.5) and 8.7 (95 % CI, 2.8-15.6) months for patients with common and uncommon EGFR mutations. Patients with OPD compared to SPD had a significantly longer time to treatment failure and longer OS of (22.9 vs. 10.8 months, p < 0.001 and 51.6 vs. 26.4 months, p = 0.004, respectively). The most common organ sites of PD were lung (62 %), brain (30 %), lymph nodes (30 %), bone (27 %) and pleura (27 %). Twenty-six patients (45 %) with OPD received local ablative treatment (LAT). The OS of OPD patients with LAT was 60.0 (95 % CI, 51.6-NA) vs. 51.4 (95 % CI 38.4-65.3) months (p = 0.43) without LAT.
The rate of OPD of patients receiving first line osimertinib was 77 %. Patients with OPD had a significantly better OS compared to patients with SPD (51.6 vs. 26.4 months). Patients with OPD receiving LAT had the longest median OS (60.0 months).
Purpose
To identify patients with metastatic urothelial cancer (mUC) unlikely to benefit from immune-checkpoint inhibitors (ICIs).
Methods/Patients
We explored the predictive and prognostic values of ...baseline neutrophil-to-lymphocyte ratio (NLR), with cut-offs ≥ 3 and ≥ 5, and of a urothelial immune prognostic index (UIPI, based on increased NLR and LDH), on 146 patients.
Results
NLR and UIPI significantly predicted progressive disease and progression-free survival with both cut-offs (
p
= 0.0069,
p
= 0.0034,
p
= 0.0160,
p
= 0.0063;
p
< 0.001,
p
= 0.021,
p
= 0.014,
p
= 0.026; for NLR-3, NLR-5, UIPI-3, UIPI-5, respectively) and overall survival when NLR cut-off was ≥ 5 (
p
= 0.03 and
p
= 0.024, for NLR-5 and UIPI-5, respectively).
Conclusions
NLR-5 deserves prospective validation to identify mUC patients with poor prognosis following ICIs.
Purpose
Metronomic oral vinorelbine (MOV) could be a treatment option for unfit patients with advanced non-small cell lung cancer (NSCLC) based on its safety profile and high patient compliance.
...Methods
We retrospectively collected data on 270 patients median age 76 (range 48–92) years, M/F 204/66, PS 0 (27)/1 (110)/≥ 2 (133), median of 3 serious comorbidities with stage IIIB-IV NSCLC treated with MOV as first (T1) (67%), second (T2) (19%) or subsequent (T3) (14%) line. Schedules consisted of vinorelbine 50 mg (138), 40 mg (68) or 30 mg (64) three times a week continuously.
Results
Patients received an overall median of 6 (range 1–25) cycles with a total of 1253 cycles delivered. The overall response rate was 17.8% with 46 partial and 2 complete responses and 119 patients (44.1%) experienced stable disease > 12 weeks with an overall disease control rate of 61.9%. Median overall time to progression was 5 (range 1–21) months T1 7 (1–21), T2 5.5 (1–19) and T3 4 (1–19) months and median overall survival 9 (range 1–36) months T1 10 (1–31), T2 8 (1–36) and T3 6.5 (2–29) months. Treatment was extremely well tolerated with 2% (25/1253) G3/4 toxicity (mainly G3 fatigue and anemia) and no toxic deaths. We observed the longer OS 14 (range 7–36) months in a subset of squamous NSCLC patients receiving immunotherapy after metronomic oral vinorelbine.
Conclusion
We confirmed MOV as an extremely safe treatment in a large real world population of advanced NSCLC with an interesting activity mainly consisting of long-term disease stabilization. We speculate the possibility of a synergistic effect with subsequent immunotherapy.
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