Lorlatinib After Alectinib-Induced Pneumonitis: A Case Report.

ALK gene rearrangements are detected in approximately 3% to 5% of NSCLC. ALK tyrosine kinase inhibitors, such as third-generation lorlatinib, have exhibited remarkable efficacy in ALK-rearranged NSCLC; however, they have been associated with a low incidence of treatment-limiting and potentially fatal drug-induced interstitial lung disease (ILD). There is concern that this may represent a class effect, a theory that is supported by a number of case reports. Because of clinical trial exclusion criteria, there are limited prospective data to guide decision-making after ALK tyrosine kinase inhibitors-induced ILD. A systematic review of the literature was conducted and only identified four reported cases of lorlatinib safety in this context. Here, we report the successful sequencing of lorlatinib in a patient who discontinued alectinib secondary to grade 3 drug-induced ILD.

How frail is frail in oncology studies? A scoping review.

AIMS: The frailty index (FI) is one way in which frailty can be quantified. While it is measured as a continuous variable, various cut-off points have been used to categorise older adults as frail or non-frail, and these have largely been validated in the acute care or community settings for older adults without cancer. This review aimed to explore which FI categories have been applied to older adults with cancer and to determine why these categories were selected by study authors. METHODS: This scoping review searched Medline, EMBASE, Cochrane, CINAHL, and Web of Science databases for studies which measured and categorised an FI in adults with cancer. Of the 1994 screened, 41 were eligible for inclusion. Data including oncological setting, FI categories, and the references or rationale for categorisation were extracted and analysed. RESULTS: The FI score used to categorise participants as frail ranged from 0.06 to 0.35, with 0.35 being the most frequently used, followed by 0.25 and 0.20. The rationale for FI categories was provided in most studies but was not always relevant. Three of the included studies using an FI > 0.35 to define frailty were frequently referenced as the rationale for subsequent studies, however, the original rationale for this categorisation was unclear. Few studies sought to determine or validate optimum FI categorises in this population. CONCLUSION: There is significant variability in how studies have categorised the FI in older adults with cancer. An FI ≥ 0.35 to categorise frailty was used most frequently, however an FI in this range has often represented at least moderate to severe frailty in other highly-cited studies. These findings contrast with a scoping review of highly-cited studies categorising FI in older adults without cancer, where an FI ≥ 0.25 was most common. Maintaining the FI as a continuous variable is likely to be beneficial until further validation studies determine optimum FI categories in this population. Differences in how the FI has been categorised, and indeed how older adults have been labelled as 'frail', limits our ability to synthesise results and to understand the impact of frailty in cancer care.

The impact of frailty on health outcomes in older adults with lung cancer: A systematic review.

BACKGROUND: Frailty is prevalent in older adults with lung cancer, however the impact of frailty in this population is not well understood. The aim of this review was to evaluate the outcomes that are measured in frail older adults with lung cancer, and to determine the associations between frailty and these outcomes. METHODS: A systematic online search of PubMed, EMBASE, and Cochrane databases was conducted to identify all English-language studies between January 2015 and May 2022 prospectively evaluating frailty and outcomes in older adults (median age > 65 years) with lung cancer. Studies were excluded if frailty was defined by a single domain assessment or not clearly defined. Quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Of 1891 studies screened, 16 met inclusion criteria. The median number of patients was 96 (range 26-494) and the mean age was 76.6 years. Eight different frailty assessments were used, and frailty definitions varied widely. The most frequently assessed outcomes were overall survival (n = 13,81%), treatment-related toxicity (n = 8,50%), hospitalisation (n = 5,31%), and treatment completion/discontinuation (n = 4,25%). Quality of life (n = 3,19%), function (n = 1,6%), frailty trajectory (n = 1,6%), and emergency visits (n = 1,6%) were infrequently assessed. Frailty had a strong and consistent association with mortality (Hazard Ratio range: 3.5-11.91). It was also associated with treatment-related toxicity and treatment selection. The remaining outcomes were not statistically significant. CONCLUSION: These data support frailty as an important predictor of mortality in older adults with lung cancer, however further research is warranted to determine the association between frailty and other meaningful endpoints for this vulnerable population.