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

Epidemiology of Cancer and Aging.- Biological Interactions of Aging and Carcinogenesis.- Replicative Senescence and Cancer.- The Influence of Advanced Age on Cancer Occurrence and Growth.- Age and Co-Morbidity in Cancer Patients: A Population-Based Approach.- Hemopoiesis and Aging.- Clinical and Biochemical Evaluation Changes Over Aging.- Biological Screening and Impact in Elderly Cancer Patients.- Biological Basis of the Association of Cancer and Aging Comorbidity.- Biological Basis of Cancer in the Older Person.- Decision Analysis for Cancer Prevention and Cancer Treatment in the Elderly.- Guidelines for the Management of the Older Cancer Patient.

Biological Basis of Geriatric Oncology

9505 Background: Drug-drug and disease-drug interactions are significant clinical issues in the elderly. Of the elderly taking 3+ chronic medications, 33% are rehospitalized within 6 months of disc...

The impact of polypharmacy on toxicity from chemotherapy in elderly patients: Focus on cytochrome P-450 inhibition and protein binding effects

Impact of age, comorbidity, and treatment characteristics on survival in older women with advanced high grade epithelial ovarian cancer.

Background Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

Phase 2 study of concurrent cetuximab plus definitive thoracic radiation therapy followed by consolidation docetaxel plus cetuximab in poor prognosis or elderly patients with locally advanced non-small cell lung cancer.

Martine Extermann

Papers

Biological Basis of Geriatric Oncology

The impact of polypharmacy on toxicity from chemotherapy in elderly patients: Focus on cytochrome P-450 inhibition and protein binding effects

Impact of age, comorbidity, and treatment characteristics on survival in older women with advanced high grade epithelial ovarian cancer.

Phase 2 study of concurrent cetuximab plus definitive thoracic radiation therapy followed by consolidation docetaxel plus cetuximab in poor prognosis or elderly patients with locally advanced non-small cell lung cancer.

The impact of fatigue and anemia on functional status in older cancer patients treated with chemotherapy