Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

/pdf/the-blockade-of-immune-checkpoints-in-cancer-immunotherapy-j2cp4ba5s9.pdf

The blockade of immune checkpoints in cancer immunotherapy

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)62167-9.pdf

Frailty in elderly people

http://www.bloodmed.com/contentimage/guidelines/3182.pdf

Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Purpose
The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).

Patients and Methods
In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs).

Results
A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain.

Conclusion
Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

Comorbidity and its treatment appear to be an important influence on the behavior of cancer in older patients. Rather than a blanket effect, this may be attached to groups of syndromes with common pathophysiological mechanisms. In addition to paying attention to the impact of cancer treatment on comorbidity, or on the impact of comorbidity on the ability to deliver cancer treatment, we will have in the future to pay attention on the direct impact of comorbidity on the behavior of the cancer in elderly patients.

Biological basis of the association of cancer and aging comorbidity.

Cancer in the Elderly: Moving the Needle Toward Evidence-Based Personalized Oncology

Background Frailty is a state of increased vulnerability to stressors, and predicts risk of adverse outcomes, such as mortality. Frailty can be defined by a frailty index (FI) using an accumulation of deficits approach. An FI comprised of 20 items derived from our previously studied test-based frailty index (TBFI) and an additional 33 survey-based elements sourced from the standard CGA was developed to evaluate if predictive validity of survival was improved. Methods One hundred eighty-nine cancer patients during acute hospitalization were consented between September 2018 and May 2019. Frailty scores were calculated, and patients were categorized into four groups: non-frail (0-0.2), mildly frail (0.2-0.3), moderately frail (0.3-0.4), and severely frail (>0.4). Patients were followed for 1-year to assess FI and TBFI prediction of survival. Area under the curve (AUC) statistics from ROC analyses were compared for the FI versus TBFI. Results Increasing frailty was similarly associated with increased risk of mortality (HR, 4.5 [95% CI, 2.519-8.075] and HR, 4.1 [95%CI, 1.692-9.942]) and the likelihood of death at 6 months was about 11-fold (odds ratio, 10.9 [95% CI, 3.97-33.24]) and 9.73-fold (95% CI, 2.85-38.50) higher for severely frail patients compared to non-frail patients for FI and TBFI, respectively. This association was independent of age and type of cancer. The FI and TBFI were predictive of survival for older and younger cancer patients with no significant differences between models in discriminating survival (FI AUC, 0.747 [95% CI, 0.6772-0.8157] and TBFI AUC, 0.724 [95% CI, 0.6513-0.7957]). Conclusions The TBFI was predictive of survival, and the addition of an in-person assessment (FI) did not greatly improve predictive validity. Increasing frailty, as measured by a TBFI, resulted in a meaningfully increased risk of mortality and may be well-suited for screening of hospitalized cancer patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.4107

Martine Extermann

Papers

Biological basis of the association of cancer and aging comorbidity.

Cancer in the Elderly: Moving the Needle Toward Evidence-Based Personalized Oncology

A simple test-based frailty index to predict survival among cancer patients with an unplanned hospitalization: An observational cohort study.

Older patients with cancer and febrile neutropenia in the COVID-19 era: A new concern.

Improved Responses with Azacitidine Compared to Decitabine in Patients with Acute Myeloid Leukemia in Patients ≥70 with Poor-Risk Cytogenetics