Association of opioid use with survival in patients with cancer treated with immune checkpoint inhibitors: it is time for evidence-based behaviors.

Cancer is a leading cause of morbidity and mortality worldwide, with pain experienced by most patients undergoing cancer treatment. Opioids are the recommended treatment for cancer pain management, but recent studies suggest a negative association between opioid use and survival rates among patients undergoing immunotherapy. However, conclusions cannot be drawn regarding causality from these observational data. Immunotherapy, which boosts the body's immune system to fight cancer cells, has emerged as a promising treatment option for all types of cancer. Immune checkpoint inhibitors (ICIs) can activate the anticancer function of exhausted T cells and have shown remarkable survival benefits in patients with multiple malignancies. However, a recent systematic review and meta-analysis suggested that the use of opioids during ICI treatment has an adverse effect on patient prognosis, while the use of NSAIDs is not significantly associated with the prognosis in patients treated with ICIs. These reviews have major limitations due to the retrospective nature of the studies and the multiple factors that can influence the phenomenon. Therefore, caution is required when interpreting results from retrospective data on drug interactions. The findings of this study are alarming and potentially harmful to patients with cancer suffering from pain or other symptoms requiring opioid drugs.

2023 MASCC/ESMO consensus antiemetic guidelines related to integrative and non-pharmacological therapies.

PURPOSE: Review the literature to propose suggestions or recommendations for controlling nausea and vomiting through integrative and non-pharmacological treatments for the MASCC/ESMO 2023 update of its antiemetic guidelines. METHODS: The authors identified available systematic reviews and/or meta-analyses for 12 integrative therapies, including acupressure, acupuncture, auricular therapy, electrical stimulation of point PC6, ginger use (i.e., Zingiber officinale), guided imagery, hypnosis, inhalation aromatherapy, music therapy, food-based interventions, progressive muscle relaxation, and reflexology. Reviews were assessed for quality through the AMSTAR2 tool. A consensus committee reviewed recommendations as per MASCC/ESMO established processes. RESULTS: Thirty-nine systematic reviews and/or meta-analyses were used. There were major methodological flaws for many of the trials used as the bases for the reviews. No recommendation for ingested ginger could be made because of conflicting evidence. Recommendations were possible for acupuncture/electroacupuncture treatments, food-based interventions, and progressive muscle relaxation training alone or combined with guided imagery. No recommendations could be reached for a number of food-based approaches, inhalation aromatherapy, hypnosis in adults, music therapy, and reflexology. CONCLUSION: While a limited number of suggestions are provided, there is a need for significantly higher quality trials in many of the therapeutic approaches assessed, before stronger recommendations and a wider range of approaches are made.

Real-world incidence and risk factors of pneumonitis in chemoradiation plus immune checkpoint inhibitors compared with chemoradiation alone in lung cancer: a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) have shown high efficacy in lung cancer. Adding ICIs to chemoradiation might increase the treatment efficacy, while the application of ICIs or chemoradiation alone can induce treatment-related pneumonitis, so whether combination therapy would increase the risk of pneumonitis needs careful evaluation. This study aimed to retrospectively analyze the incidence of pneumonitis in patients who underwent chemoradiation combined with ICIs compared with chemoradiation alone and explore the risk factors of pneumonitis in combination therapy. Methods: This was a retrospective cohort study. Patients who received conventional thoracic radiation with a minimum total dose of 50 Gy for lung cancer between January 2020 and December 2021 at West China Hospital were retrospectively reviewed and followed up for at least 6 months after radiation. Patients were divided into two groups according to whether chemoradiation was administered with or without ICIs. Pneumonitis was evaluated by chest computed tomography (CT) at least every 2 months in outpatient department. The clinical characteristics, including sex, age, smoking history, pathological diagnosis, baseline pulmonary disease [including chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD)], treatment strategy, location of primary tumor and radiological dosimetric parameters were recorded. Chi-squared tests or Fisher's exact tests were performed to analyze the difference between the combination group and control group for categorical variables and Mann-Whitney U test for continuous variables. Univariate and multivariate analyses were performed by logistic regression. Results: A total of 152 patients who received chemoradiation were enrolled. The median age was 59 years. A total of 115 (75.7%) patients were non-small cell lung cancer (NSCLC), 22 (14.5%) were small cell lung cancer (SCLC), and 15 (9.9%) were other pathological types. Among them, 58 received chemoradiation combined with ICIs and 94 received chemoradiation alone. The rate of grade ≥2 pneumonitis was significantly higher in the combination therapy group (39.7% vs. 22.3%, P=0.028) and was associated with the use of ICIs [odds ratio (OR): 2.641, 95% confidence interval (CI): 1.244-5.608, P=0.011] and percent volume of the lung receiving ≥30 Gy (V30) (OR: 1.728, 95% CI: 1.214-2.460, P=0.002). The history of chronic lung disease was the independent risk factor (OR: 6.359, 95% CI: 1.953-20.705, P=0.002) of grade ≥3 pneumonitis. In the combination group, univariate and multivariate analyses revealed that V5, V20, V30, and mean lung dose (MLD) were not associated with pneumonitis, whereas the history of chronic lung disease was an independent risk factor of grade ≥3 pneumonitis (OR: 8.351, 95% CI: 1.469-47.484, P=0.017). Conclusions: The incidence of pneumonitis of ICIs combined with chemoradiation was higher than chemoradiation alone, but manageable. The combination therapy should be applied with caution especially in patients with history of chronic lung disease.

Safety and efficacy outcomes of early cessation of anti-PD1 therapy in patients 80 years or older: A retrospective cohort study.

Older patients have similar immune checkpoint inhibitor efficacy and rates of adverse events as younger patients, but appear to have decreased tolerability, particularly in the oldest patient cohort (>80 years), often leading to early cessation of therapy. We aimed to determine whether early discontinuation impacts efficacy of anti-PD-1 therapy in patients ≥80 years old. In this retrospective, multicenter, international cohort study, we examined 773 patients with 4 tumor types who were at least 80 years old and treated with anti-PD-1 therapy. We determined response rate, overall survival (OS), and progression-free survival (PFS) in patients who discontinued therapy early (<12 months) for reasons other than progression or death. We used descriptive statistics for demographics, response, and toxicity rates. Survival statistics were described using Kaplan Meier curves. Median (range) age at anti-PD-1 initiation was 83.0 (75.8-97.0) years. The cancer types included were melanoma (n = 286), non-small cell lung cancer (NSCLC) (n = 345), urothelial cell carcinoma (UCC) (n = 108), and renal cell carcinoma (RCC) (n = 34). Of these, 102 met the primary endpoint of <12 months to discontinuation for reasons other than death or progression. Median PFS and OS, respectively, for these patients were 34.4 months and 46.6 months for melanoma, 15.8 months and 23.4 months for NSCLC, and 10.4 months and 15.8 months for UCC. This study suggests geriatric patients who have demonstrated therapeutic benefit and discontinued anti-PD-1 therapy at less than 12 months of duration for reasons other than progression may have durable clinical benefit without additional therapy.

Comparing efficacy and safety of upfront treatment strategies for anaplastic lymphoma kinase-positive non-small cell lung cancer: a network meta-analysis.

Aim: This article is based on our previous research, which was presented as a post at the Congress Aiom 2022 Congress and published in Tumori Journal as Conference Abstract (Tumori J. 2022;108:1-194. doi: 10.1177/03008916221114500). In this paper, a comprehensive presentation of all the achieved results is provided. Several tyrosine kinase inhibitors (TKIs) have been investigated to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). However, direct comparisons between these TKIs are lacking, with many only being compared to crizotinib. To address this gap, a network meta-analysis was conducted to compare the efficacy and safety of various first-line systemic therapies for ALK-positive NSCLC. Methods: A thorough search of PubMed, Embase, and Cochrane Library was performed to identify randomized controlled trials (RCTs) published between January 01, 2000 and April 01, 2022, and included trials that investigated upfront treatments for this molecular subgroup and reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of grade 3 or higher (grade ≥ 3 AEs). Results: The analysis included 9 RCTs with 2,443 patients receiving eight different treatments: alectinib (at two different dosages), brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Second and third-generation TKIs significantly prolonged PFS compared to crizotinib, with lorlatinib having the highest probability of yielding the most favorable PFS, followed by alectinib (300 mg or 600 mg). However, only alectinib has been shown to significantly prolong OS compared to crizotinib to date. Lorlatinib appears superior in reducing the risk of central nervous system (CNS) progression, followed by alectinib 600 mg. Ceritinib had the highest rate of AEs, followed by lorlatinib and brigatinib. Conclusions: Based on the network meta-analysis, alectinib and lorlatinib emerged as the most promising upfront treatment options. These treatments provide prolonged disease control while maintaining an acceptable safety profile.