Anti-PD-(L)1 for KRAS-mutant advanced non-small-cell lung cancers: a meta-analysis of randomized-controlled trials.

PURPOSE: The most frequent mutation in advanced non-small-cell lung cancer (NSCLC), Kirsten rat-sarcoma viral oncogene (KRAS) is found in 20-25% of these patients' tumors. While phase III trials on therapies targeting KRAS, especially KRASG12C, are ongoing, the clinical efficacy of anti-programmed death protein-1 (PD-1) or its ligand (PD-L1) against KRAS-mutant NSCLCs remains a topic of debate. METHODS: This meta-analysis examined randomized-trial data comparing first- or second-line anti-PD-(L)1 with or without chemotherapy vs. chemotherapy alone for advanced KRAS-mutant NSCLCs. Outcome measures included overall survival (OS) and progression-free survival (PFS). Analyses were computed using the Cochrane method of collaboration for meta-analyses, with Review Manager software (RevMan version 5.3; Oxford, UK). RESULTS: We analyzed 3 first-line trials (IMpower-150, Keynote-189 and Keynote-042) and 3 second-line trials (Oak, Poplar and CheckMate-057) that included 1313 NSCLCs (386 KRAS-mutant and 927 KRAS wild-type tumors). For KRAS-mutant NSCLCs, anti-PD-(L)1 with or without chemotherapy was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.59 [0.49-0.72]; p < 0.00001) and PFS (0.58 [0.43-0.78]; p = 0.0003) compared to chemotherapy alone. OS benefited in both first- and second-line trials. OS for patients with KRAS-mutant NSCLCs was significantly longer than that for those with KRAS wild-type tumors (p = 0.001). CONCLUSIONS: Anti-PD-(L)1 with or without chemotherapy seemed to achieve longer OS and PFS than chemotherapy alone for patients with KRAS-mutant and wild-type KRAS advanced NSCLCs, with an even greater OS benefit for the former.

Impact of the addition of bevacizumab, oxaliplatin, or irinotecan to fluoropyrimidin in the first-line treatment of metastatic colorectal cancer in elderly patients.

INTRODUCTION: The clinical benefit of double-front-line therapy (including oxaliplatin or irinotecan or bevacizumab plus 5-fluorouracil (5FU) or capecitabine) compared to monotherapy (5FU or capecitabine) in elderly (> 70 years) patients with metastatic colorectal cancer (MCRC) is controversial. We performed a meta-analysis of published randomized studies. MATERIALS AND METHODS: The selection of the studies was carried out using PubMed with the following keywords: "metastatic colorectal cancer," "elderly," "oxaliplatin," "irinotecan," "bevacizumab," "survival." The efficacy endpoints were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. By convention, an HR < 1 was a result in favor of biotherapy. RESULTS: This meta-analysis (MA) included ten studies: three assessing irinotecan (FFCD 2001-02, CAIRO, and an already published MA by Folprecht), three assessing oxaliplatin (FOCUS2, FFCD 2000-05, and a published study by De Gramont), and four assessing bevacizumab (PRODIGE-20, AVEX, AGITG-MAX, and "AVF2192g" by Kabbinavar). Our MA included 1652 patients (62% of men). Concerning age, we chose a cut-off of 70 years or a cut-off of 75 years, corresponding to the available data for each study. The performance index (PS) was 0-1 for about 90% of patients, with the exception of FFCD 2001-02 and FOCUS2 which included 30% of patients with PS2. Overall, the addition of bevacizumab to fluoropyrimidin statistically improves both OS and PFS (HR = 0.78; CI 0.63-0.96 and HR = 0.55; CI 0.44-0.67, respectively). The addition of oxaliplatin did not statistically improve OS (= 0.99; CI 0.85-1.17) but improves PFS (HR = 0.81; CI 0.67-0.97) as well as the addition of irinotecan (HR = 1.01; CI 0.84-1.22 and HR = 0.82; CI 0.68-1.00, respectively). CONCLUSION: In previously untreated elderly patients with MCRC, the addition of bevacizumab to fluoropyrimidin appears more effective in terms of OS or PFS than the addition of oxaliplatin or irinotecan.

[Checkpoint inhibitors, the perspectives for elderly patients]. / Inhibiteurs de "check point", quelles perspectives pour les patients âgés ?

The arrival of new immunotherapies, called checkpoint inhibitors, is radically changing the world of oncology. Currently, there are some twenty different cancers which may respond to this type of therapy. It is therefore important that professionals involved in the care of elderly people with cancer are already made aware of these new treatments. This article explains how these checkpoint inhibitors work and describes their efficacy and their toxicity for elderly patients.

Doublet chemotherapy vs. single-agent therapy with 5FU in elderly patients with metastatic colorectal cancer. a meta-analysis.

BACKGROUND: The clinical benefit of first-line doublet chemotherapy (including oxaliplatin or irinotecan) compared to single-drug therapy (5FU) in elderly patients (>70 or >75 years old) with metastatic colorectal cancer (MCRC) is controversial. Therefore, we undertook a meta-analysis of all published phase III studies. MATERIAL AND METHODS: We performed a PubMed search using keywords metastatic colorectal cancer, phase III studies, oxaliplatin, irinotecan, survival. We also screened Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) proceedings. Few studies have been published corresponding to our inclusion criteria. The efficacy outcomes were overall survival (OS) and progression-free survival (PFS). Toxicity was also examined when available. Hazard ratios (HRs) with their 95 % confidence intervals (CI) were collected from the studies and pooled. By convention, HRs <1 corresponded to a better outcome for doublets. p values <0.05 were considered statistically significant. A fixed-effect model was used. We used Comprehensive Meta-Analysis Software (Biostat, Englewood, NJ, USA). RESULTS: This meta-analysis (MA) included five original studies (Mitry and Venderbosch for CAIRO both assessing irinotecan, De Gramont and Seymour for FOCUS2 and Ducreux assessing oxaliplatin) and an already published MA (Folprecht) of four trials comparing FOLFIRI with 5FU (Saltz, Douillard, Köhne and Seymour). Our MA included 1225 patients (70 % men). For age, we chose a cut-off of 70 years for oxaliplatin and a cut-off of 75 years for irinotecan. The performance status (PS) score was 0-1 in about 90 % of patients except for the studies by Mitry and Seymour FOCUS2 which both included 30 % of PS2 patients. Overall, doublet chemotherapy, compared to 5FU alone, did not improve OS (HR = 1.00; CI: 0.89-1.13) but significantly improved PFS (HR = 0.82; CI: 0.72-0.93). When assessed separately, FOLFIRI and FOLFOX both significantly improved PFS (HR = 0.83; 0.68-1.00 and HR = 0.81; 0.68-0.97, respectively). The main grade 3-4 toxicities for FOLFIRI were diarrhoea, nausea, vomiting and neutropenia, which occurred significantly more often than with 5FU alone. CONCLUSION: Addition of oxaliplatin or irinotecan to 5FU in metastatic CRC significantly improved PFS in elderly patients more than 70 years old but was associated with an increased risk of toxicity as shown for irinotecan.

Clinical benefit of anti-PD-1/PD-L1 plus chemotherapy in first-line treatment for patients over the age of 65 or 75 with metastatic non-small cell lung cancer (NSCLC).

Anti-PD-1/PD-L1 plus chemotherapy (CT) is considered the standard of care in first line treatment of metastatic NSCLC. However, the clinical benefit of this combination in older patients is controversial. We performed a meta-analysis of phase III randomized trials that compared PD-1/PD-L1 inhibitor plus CT with CT alone in first line of treatment for older patients with advanced NSCLC. Subgroups of patients over 65 and over 75 were analyzed. The outcomes included overall survival (OS) and progression-free survival (PFS). A fixedeffect model was used. We analyzed ten trials with an anti-PD-1 (camrelizumab, cemiplimab, nivolumab, pembrolizumab, tislelizumab or toripalimab) and six trials with an anti-PD-L1 (atezolizumab, durvalumab or sugemalimab), including 3666 patients over the age of 65 (41%) and 282 patients over the age of 75 (<10%). For patients over 65 years of age, anti-PD- 1/PD-L1 + CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.79 [0.72-0.86]; p < 0.00001) and P FS (0.63 [0.58-0.68]; p < 0.00001) compared to CT alone. Survival benefits occurred in both anti-PD-1 and anti-PD-L1 trials. For patients over 75 years of age, OS benefit was not statistically significant (0.88 [0.67-1.16]; p = 0.37). For patients over the age of 65 with untreated NSCLC, the anti-PD-1/PD-L1 combination with CT, compared with CT alone, is associated with significantly improved OS and PFS. Due to the low number of patients, it is difficult to conclude for those over 75.

First-line concomitant EGFR-TKI + chemotherapy versus EGFR-TKI alone for advanced EGFR-mutated NSCLC: a meta-analysis of randomized phase III trials.

INTRODUCTION: A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (EGFR) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest. METHODS: We conducted a meta-analysis of phase III randomized trials comparing EGFR-TKI + ChT vs. EGFR-TKI alone as first-line therapy for advanced NSCLC harboring an activating EGFR mutation. RESULTS: Three studies evaluated gefitinib + ChT (NEJ009, GAP-Brain, and Noronha et al.) and another evaluated osimertinib + ChT (FLAURA-2). Those four eligible studies included 1413 patients with non-squamous NSCLCs, 826 (58%) with an exon-19 deletion (ex19del) and 541 (38%) with EGFRL858R. The EGFR-TKI + ChT combination was significantly associated with prolonged PFS (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.45-0.59]; p < 0.0001) and OS (HR: 0.69 [0.52-0.93]; p = 0.01). PFS was particularly improved for patients with brain metastases (HR: 0.41[0.33-0.51]; p < 0.00001). CONCLUSIONS: For patients with untreated, advanced, EGFR-mutated NSCLCs, the EGFR-TKI + ChT combination, compared to EGFR-TKI alone, was associated with significantly prolonged PFS and OS. However, further studies are needed to identify which patients will benefit the most from the combination. REGISTRATION: PROSPERO CRD42024508055.

[Assessment of nursing needs and risk management in geriatric oncology]. / Evaluation des besoins en soins et gestion des risques en oncogériatrie.

In France, the incidence and rate of mortality of cancer increase with age. For elderly patients suffering from cancer, the standard geriatric assessment, together with an oncological assessment aims to optimise the treatment. This geriatric oncology assessment enables the priorities to be identified and the cancer treatment to be adapted by anticipating the risks and organising the support care.

Is There a Benefit of Oxaliplatin in Combination with Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer? An Updated Meta-Analysis.

BACKGROUND: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear. METHODS: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until March 2021, we searched PubMed and the Cochrane Library. We also searched for relevant ASCO conference abstracts. The primary endpoint was disease-free survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3). RESULTS: A total of seven randomized clinical trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6, and STAR-01) with 5782 stage II or III rectal cancer patients were analyzed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone. Compared with the 5FU alone group, the OXP + 5FU regimen improved DFS (HR = 0.90, 95% CI: 0.81-0.99, p = 0.03) and pathologic complete response (pCR) (OR = 1.21, 95% CI: 1.07-1.37, p = 0.002). Patients treated with the OXP + 5FU regimen had significantly less metastatic progression (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering adverse events (AEs), there was more grade 3-4 diarrhea with OXP + 5FU (OR = 2.41, 95% CI: 1.74-3.32, p < 0.00001). However, there were no significant differences grade 3-4 hematologic AEs (OR = 1.16, 95% CI: 0.87-1.57, p = 0.31). CONCLUSIONS: Our meta-analysis with long-term results from the randomized studies showed a benefit of the addition of OXP + 5FU regiment in terms of DFS, metastatic progression, and pCR rate that did not translate to improved OS.

Impact on All-Cause and Cardiovascular Mortality Rates of Coronary Artery Calcifications Detected during Organized, Low-Dose, Computed-Tomography Screening for Lung Cancer: Systematic Literature Review and Meta-Analysis.

Although organized, low-dose, computed-tomography (CT) scan lung-cancer screening has been shown to lower all-cause and lung-cancer-specific mortality, the primary cause of death for subjects eligible for such screening remains cardiovascular (CV) mortality. This meta-analysis study was undertaken to evaluate the impact of screening-scan-detected coronary artery calcifications (CACs) on CV and all-cause mortality. We conducted a systematic review and meta-analysis of studies reporting CV mortality according to the Agatson CAC score for participants in a lung-cancer screening program of randomized clinical or cohort studies. PubMed, Embase, and Cochrane databases were screened in June 2020. Two authors independently selected articles and extracted data. Six studies, including 20,175 subjects, were retained. CV and all-cause mortality rates were higher for subjects with CAC scores >0, with respective relative risks of 2.02 [95% CI 1.23-3.32] and 2.29 [95% CI 1.00-5.21]. Both mortality rates were even higher for those with high CAC scores (>400 or >1000). CACs are more common in men than in women, with an odds ratio of 1.49 [95% CI 1.40-1.59]. The presence of CAC is associated with CV mortality with an RR of 2.05 [95% CI 1.20-3.57] in men and 2.37 [CI 95% 1.29-5.09] in women, respectively. Analysis of lung-cancer-screening scans for CACs is a tool able to predict CV mortality. Prospective studies within those programs are needed to assess the benefit of primary CV prevention based on CAC detection.

First-line PD-1/PD-L1 inhibitor plus chemotherapy vs chemotherapy alone for negative or < 1% PD-L1-expressing metastatic non-small-cell lung cancers.

AIMS: Single-agent anti-PD-1/PD-L1 clinical efficacy against < 1% PD-L1-expressing non-small-cell lung cancers (NSCLCs) is controversial. METHODS: This meta-analysis examined randomized-trial data comparing first-line PD-1/PD-L1-inhibitor + chemotherapy (CT) vs CT alone for advanced < 1% PD-L1 NSCLCs. Outcome measures included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). RESULTS: IMpower (atezolizumab + CT), Keynote (pembrolizumab + CT) and CheckMate (nivolumab + CT) trials included 2037 NSCLCs (1246 PD-L1-negative; 791 < 1% PD-L1 expression). Anti-PD-1/PD-L1 + CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.75 [0.63-0.89]; p = 0.0008) and PFS (0.72 [0.65-0.80]; p < 0.0001), and higher ORR (odds ratio 2.06 [1.50-2.83]; p < 0.0001). CONCLUSIONS: First-line anti-PD-1/PD-L1 + CT combination appears superior to CT alone for advanced, < 1% PD-L1-expressing NSCLCs for OS, PFS and ORR.

First-line angiogenesis inhibitor plus erlotinib versus erlotinib alone for advanced non-small-cell lung cancer harboring an EGFR mutation.

PURPOSE: Erlotinib is indicated as first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor-receptor (EGFR) mutation. Addition of a vascular endothelial growth factor (VEGF) inhibitor (anti-VEGF) in combination with the tyrosine-kinase inhibitor erlotinib in this setting is controversial. METHODS: We conducted a meta-analysis of randomized trials comparing anti-VEGF plus erlotinib vs erlotinib alone as first-line therapy for advanced NSCLC harboring an EGFR mutation. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and median duration of response (DOR). A fixed-effect model was used. RESULTS: Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al.), and another evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients, 654 (53.2%) with exon 19 deletion (ex19del) and 568 (46.8%) with EGFRL858R. Patients were predominantly women (63%), Asians (85%) and non-smokers (60%); the median age was 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with prolonged PFS (hazards ratio [HR] 0.59 [95% confidence interval (CI) 0.51-0.69]; p < 0.00001). The combination achieved significantly longer median DOR (p < 0.005). Based on interim analyses, OS (HR 0.90 [0.68-1.19]; p = 0.45) and ORR (odds ratio 1.19 [95% CI 0.91-1.55]; p = 0.21 were comparable. CONCLUSIONS: For patients with untreated, advanced, EGFR-mutation-harboring NSCLCs, the anti-VEGF + erlotinib combination, compared to erlotinib alone, was associated with significantly prolonged PFS but mature data for OS are needed to confirm the benefit of this strategy.

First-line immune-checkpoint inhibitor plus chemotherapy versus chemotherapy alone for extensive-stage small-cell lung cancer: a meta-analysis.

INTRODUCTION: Platin-based chemotherapy (CT) has long been the first-line standard-of-care for patients with extensive-stage small-cell lung cancer (ES-SCLC). Adding immune-checkpoint inhibitor(s) to CT (ICI+CT) in this setting is an option of interest, although its benefit is apparently modest. METHODS: This meta-analysis was conducted on randomized trials comparing first-line ICI+CT versus CT alone for ES-SCLC. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), response at 12 months and adverse events (AEs). Subgroup analyses were computed according to the immunotherapy used, performance status (PS), age, platinum salt, liver metastases and brain metastases at diagnosis. RESULTS: The literature search identified one randomized phase II (ECOG-ACRIN-5161) and four phase III trials (CASPIAN, IMPOWER-133, KEYNOTE-604 and Reck et al. 2016) that included 2775 patients (66% males, 95% smokers, median age: 64 years, PS = 0 or 1). ICI+CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS [0.82 (0.75-0.89); p < 0.00001] and PFS [0.81 (0.75-0.87); p < 0.00001], with OS benefits for anti-PD-L1 [0.73 (0.63-0.85); p < 0.0001] or anti-PD-1 [0.76 (0.63-0.93); p < 0.006] but not for anti-CTLA-4 [0.90 (0.80-1.01), p = 0.07]. ORRs for ICI+CT or CT alone were comparable [odds ratio 1.12 (0.97-1.00); p = 0.12], but responses at 12 months favored ICI+CT [4.16 (2.81-6.17), p < 0.00001]. Serious grade-3/4 AEs were more frequent with ICI+CT [odds ratio 1.18 (1.02-1.37); p = 0.03]. Compared with CT, no ICI+CT benefit was found for ES-SCLC with brain metastases at diagnosis [HR 1.14 (0.87-1.50); p = 0.34]. CONCLUSIONS: First-line ICI+CT appears to be superior to CT alone for ES-SCLC except for patients with brain metastases at diagnosis.

Immune Checkpoint Inhibitors for Patients Aged ≥ 75 Years with Advanced Cancer in First- and Second-Line Settings: A Meta-Analysis.

BACKGROUND: The impact of aging on the effectiveness of immune checkpoint inhibitors (ICIs) remains controversial, and little is known on the subject in adults aged ≥ 75 years. OBJECTIVE: The objective of this comprehensive meta-analysis was to assess the efficacy of ICIs in patients aged ≥ 75 years. METHODS: We performed a meta-analysis of published randomized controlled trials concerning ICIs (as monotherapy or in combination) versus standard therapy in patients with advanced solid tumors between January 2010 and January 2020. We compared overall survival between older (aged ≥ 75 years) and younger (< 75 years) patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected and pooled. The secondary endpoint focused on the impact of the use of ICIs in first- and second-line settings. RESULTS: In total, 15 phase III studies evaluating anti-programmed cell death 1 (anti-PD-1) (nivolumab or pembrolizumab), anti-programmed cell death ligand 1 (anti-PD-L1) (atezolizumab or avelumab), or anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) (ipilimumab) therapies were included. Enrolled patients had non-small-cell lung cancer, renal cell carcinoma, melanoma, head and neck squamous cell carcinoma, or gastric cancer. Eight studies assessed treatment in the first-line setting and seven in the second-line setting. The median age was 64 years, with 906 patients aged ≥ 75 years (552 in first line, 354 in second line) and 8741 were aged < 75 years (4992 in first line, 3749 in second line). In the first-line setting, HRs for death were 0.78 (95% CI 0.61-0.99) in patients aged ≥ 75 years versus 0.84 (95% CI 0.71-1.00) in those aged < 75 years. In the second-line setting, HRs for death were 1.02 (95% CI 0.77-1.36) in patients aged ≥ 75 years versus 0.68 (95% CI 0.61-0.75) in those aged < 75 years, with a statistically significant difference observed between subgroups (p = 0.009 for interaction). CONCLUSIONS: ICIs appear to be effective in patients aged ≥ 75 years. However, the survival benefit is mainly observed in first-line treatment and remains unclear in the second-line setting.

Is There a Benefit of Addition Docetaxel, Abiraterone, Celecoxib, or Zoledronic Acid in Initial Treatments for Patients Older Than 70 Years With Hormone-sensitive Advanced Prostate Cancer? A Meta-analysis.

BACKGROUND: Results from large randomized controlled trials combining docetaxel, abiraterone, celecoxib, or bisphosphonates with androgen deprivation therapy (ADT) in hormone-sensitive prostate cancer have emerged. However, in our knowledge, few data are available in patients older than 70 years. Therefore, we undertook a meta-analysis of all published phase III studies. MATERIALS AND METHODS: We performed a PubMed search using the keywords: "hormone sensitive prostate cancer," "phase III studies," "docetaxel," "abiraterone," "celecoxib," and "bisphosphonates." We also screened American Society of Clinical Oncology and European Society for Medical Oncology proceedings. Combination therapies were compared with ADT alone. The efficacy outcomes were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. A hazard ratio of less than 1.00 favored the combination group. RESULTS: This meta-analysis included 8 studies: 3 assessed docetaxel (CHAARTED, STAMPEDE arm E and C), 2 others assessed abiraterone (LATITUDE and STAMPEDE arm G); 2 others assessed celecoxib (STAMPEDE arm D and F), and the last one assessed zoledronic acid alone (STAMPEDE arm B). Our meta-analysis included 2264 patients (86% with metastases). Concerning age, we chose a cutoff of 70 years, corresponding to the available data for each study. The performance index was 0 to 1 for about 90% of patients. Overall, in patients > 70 years old, the addition of docetaxel statistically improved PFS (HR, 0.51; 95% CI, 0.42-0.61) but not OS (HR, 0.86; 95% CI, 0.69-1.07). The addition of abiraterone to ADT also statistically improved PFS (HR, 0.49; 95% CI, 0.37-0.64) but not OS (HR, 0.85; 95% CI, 0.67-1.08), as well as the addition of celecoxib (HR, 0.67; 95% CI, 0.53-0.85 and HR, 0.95; 95% CI, 0.73-1.25, respectively). The addition of zoledronic acid did not improve PFS or OS (HR, 0.78; 95% CI, 0.61-1.00 and HR, 0.99; 95% CI, 0.71-1.38, respectively). CONCLUSIONS: The addition of docetaxel, abiraterone, or celecoxib to ADT significantly increased PFS in older men with hormone-sensitive advanced prostate cancer. However, the benefit in OS is not statistically significant. Further studies are needed to define the best first-line strategy in this subgroup.

Chronological Age and Risk of Chemotherapy Nonfeasibility: A Real-Life Cohort Study of 153 Stage II or III Colorectal Cancer Patients Given Adjuvant-modified FOLFOX6.

OBJECTIVES: To assess nonfeasibility of adjuvant-modified FOLFOX6 chemotherapy in patients with stage II or III colorectal cancer. METHODS: Consecutive patients managed between 2009 and 2013 in 2 teaching hospitals in the Paris urban area were included in the CORSAGE (COlorectal canceR, AGe, and chemotherapy fEasability study) cohort study. Nonfeasibility was defined by the frequencies of empirical first-cycle dose reduction (>15%), early discontinuation (<12 cycles), and low relative dose intensity (RDI) (<0.85). Risk factors for chemotherapy nonfeasibility were identified using multivariate logistic regression. RESULTS: Among 153 patients, 56.2% were male (median age, 65.6 y; 35.3%≥70 y; 7.3% with performance status [PS]≥2). For 5-fluorouracil (5-FU), 20.9% of patients had first-cycle dose reduction and 28.1% early discontinuation; RDI was 0.91 (25th to 75th percentiles, 0.68 to 0.99). Factors independently associated with first-cycle 5-FU dose reduction were aged 65 to 69 years versus those younger than 65 years (adjusted odds ratio [aOR], 5.5; 95% confidence interval [CI], 1.5-19.9) but not age 70 years and older, PS≥2 (aOR, 6.02; 95% CI, 1.15-31.4), higher Charlson Comorbidity Index (aOR1-point increase, 1.4; 95% CI, 1.05-1.82), or larger number of medications (aOR 1-medication increase, 1.19; 95% CI, 1.00-1.42). Oxaliplatin dose reduction occurred in 52.3% of patients and early discontinuation in 62.7%; the latter was more common in the 70 years and older group (92.6% vs. 74.6% in the <65-y group; P=0.01); RDI was 0.7 (95% CI, 0.55-0.88). CONCLUSIONS: In the real-world setting, compared with their younger and older counterparts, patients aged 65 to 69 years given modified FOLFOX6 for stage II or III colorectal cancer had higher frequencies of 5-FU nonfeasibility defined based on first-cycle dose reduction, early discontinuation, and RDI; and these differences were independent from PS, comorbidities, and number of medications.

Is There a Survival Benefit of First-Line Epidermal Growth Factor Receptor Tyrosine-Kinase Inhibitor Monotherapy Versus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer?: A Meta-Analysis.

BACKGROUND: Tyrosine-kinase inhibitors (TKIs) markedly improve progression-free survival (PFS) of patients with advanced non-small-cell lung cancer (NSCLC) mutated for epidermal growth factor receptor (EGFR). Results on overall survival (OS) are less clear-cut. We performed a publication-based meta-analysis to address further this issue. METHODS: We did a PubMed query using keywords simultaneously (lung neoplasm, tyrosine kinase inhibitors, epidermal growth factor receptor mutation, survival, and randomized controlled trials). We also searched for relevant abstracts in annual proceedings of ASCO, ESMO, and WCLC meetings. We cross-checked all references from all eligible articles. Only phase III randomized controlled trials comparing TKI monotherapy and platinum-based doublet chemotherapy in first-line treatment of metastatic or advanced NSCLC were included. We used EasyMA software to perform statistical analyses. A random effect model was used in case of heterogeneity between studies (and a fixed effect model in absence of heterogeneity). RESULTS: The eight eligible studies included 2962 patients (780 males, 2182 females, mostly Asian, median age 60 years), 2909 adenocarcinomas (98 %), 1739 mutated tumors (897 exon 19 deletion, 699 L858 mutation), 448 stage IIIB, and 2222 stage IV (75 %) tumours and 2453 never smokers (83 %). Four studies assessed gefitinib, two studies assessed erlotinib, and two studies assessed afatinib. Chemotherapies were doublets including a platinum salt. All studies included patients with EGFR mutations, but six studies included only EGFR mutated patients. OS was similar among patients who first received TKI or chemotherapy (HR 0.98, 95 % CI 0.87-1.10, fixed effect model). Conversely, compared with chemotherapy, EGFR TKIs significantly improved PFS in patients with EGFR-mutated tumours (HR 0.37, 95 % CI 0.29-0.49, random effect model). Concerning side effects, rash (RR 6.29, 95 % CI 4.05-9.77), diarrhoea (RR 3.51, 95 % CI 2.15-5.75), stomatitis (RR 3.57, 95 % CI 1.81-7.04), and interstitial lung disease (RR 6.07, 95 % CI 1.66-22.2) were significantly more frequent after TKIs. As expected, fatigue (RR 0.38, 95 % CI 0.32-0.45), nausea/vomiting (RR 0.19, 95 % CI 0.11-0.32), and haematological disorders, including thrombocytopenia (RR 0.18, 95 % CI 0.09-0.35), anaemia (RR 0.22, 95 % CI 0.15-0.33), and grade 3-4 neutropenia (RR 0.06, 95 % CI 0.04-0.08), were significantly more frequent after chemotherapy. CONCLUSION: The major discrepancy between a similar OS and a markedly improved PFS after first-line TKI compared with chemotherapy could be related to the high level of crossing-over between both groups.

Measurement of gait speed in older adults to identify complications associated with frailty: A systematic review.

Several frailty screening tests in older cancer patients were developed but their statistical performance is low. We aimed to assess whether measurement of usual gait speed (GS) alone could be used as a frailty screening test in older cancer patients. This systematic review was conducted on "pub med" between 1984 and 2014 and included reviews and original studies. Eligibility criteria were: GS over a short distance, alone or included in composite walking tests (Timed Get Up and Go test: TGUG, Short Physical Performance Battery: SPPB) in older people (aged 65 and over) living in a community setting and predictive value of GS on medical complications associated with frailty. 46 articles were finally selected. GS alone is consensual and recommended for screening sarcopenia in elderly. A slow GS is predictive of early death, disability, falls and hospitalization/institutionalization in older people living in a community setting. GS alone is comparable to composite walking tests that do not provide additional information on the medical complications associated with frailty. Despite few studies in geriatric oncology, GS seems to predict overall survival and disability. We suggest GS over 4m (at a threshold of 1m/s) as a new frailty screening test in older cancer patients (65 and over) to guide the implementation of a comprehensive geriatric assessment during the initial management phase or during follow-up. Prospective cohort studies are needed to validate this algorithm and compare it with other screening tool.

Similar survival rates with first-line gefitinib, gemcitabine, or docetaxel in a randomized phase II trial in elderly patients with advanced non-small cell lung cancer and a poor performance status (IFCT-0301).

OBJECTIVES: We evaluated the impact of age in a randomized phase II trial that compared three first-line drugs in elderly patients with advanced non-small cell lung cancer (NSCLC) and a poor performance status (PS). MATERIALS AND METHODS: Patients with advanced NSCLC with a PS of 2 or 3 were enrolled into a multicenter randomized trial: arm A, gefitinib; arm B, gemcitabine; and arm C, docetaxel. We performed subgroup analyses according to age. RESULTS: Between December 2004 and June 2007, 127 patients were enrolled. Analyses were performed between the two subgroups aged <70years (younger, n=56) and ≥70years (older, n=71). Patients mainly had adenocarcinoma (46% young vs. 51%: elderly), of which 62% vs. 75% had a PS of 2, respectively. Significantly more elderly patients were women and non-smokers, and there was a non-significant trend towards more PS-2 among the elderly. Progression-free survival (PFS) was 1.4months (95% CI: 1.1-1.9) for younger compared to 2.3months (95% CI: 2.1-2.9) for elderly patients. Overall survival (OS) was 2.0months (95% CI: 1.5-2.4) and 3.7months (95% CI: 2.4-4.8), respectively. Toxicity did not differ between younger and older patients. NSCLC was better controlled in elderly patients after three cycles of monotherapy compared to younger patients (p=0.034). When adjusted for stratification criteria, age was the main prognostic factor for PFS. Adjusted HRs for PFS was 0.57 (95% CI: 0.38-0.85) for the elderly compared to patients aged <70years (p=0.004). CONCLUSIONS: Older patients had a decreased risk of progression/death compared to younger patients. Single-agent chemotherapy can be considered for patients aged ≥70years with a PS of 2.