Re-irradiation for recurrent intracranial meningiomas: Analysis of clinical outcomes and prognostic factors.

PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities. MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/ß = 2 for brain tissue and α/ß = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis. RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively). CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.

Stereotactic Body Radiation Therapy and Abiraterone Acetate for Patients Affected by Oligometastatic Castrate-Resistant Prostate Cancer: A Randomized Phase II Trial (ARTO).

PURPOSE: ARTO (ClinicalTrials.gov identifier: NCT03449719) is a multicenter, phase II randomized clinical trial testing the benefit of adding stereotactic body radiation therapy (SBRT) to abiraterone acetate and prednisone (AAP) in patients with oligometastatic castrate-resistant prostate cancer (CRPC). MATERIALS AND METHODS: All patients were affected by oligometastatic CRPC as defined as three or less nonvisceral metastatic lesions. Patients were randomly assigned 1:1 to receive either AAP alone (control arm) or AAP with concomitant SBRT to all the sites of disease (experimental arm). Primary end point was the rate of biochemical response (BR), defined as a prostate-specific antigen (PSA) decrease ≥50% from baseline measured at 6 months from treatment start. Complete BR (CBR), defined as PSA < 0.2 ng/mL at 6 months from treatment, and progression-free survival (PFS) were secondary end points. RESULTS: One hundred and fifty-seven patients were enrolled between January 2019 and September 2022. BR was detected in 79.6% of patients (92% v 68.3% in the experimental v control arm, respectively), with an odds ratio (OR) of 5.34 (95% CI, 2.05 to 13.88; P = .001) in favor of the experimental arm. CBR was detected in 38.8% of patients (56% v 23.2% in the experimental v control arm, respectively), with an OR of 4.22 (95% CI, 2.12 to 8.38; P < .001). SBRT yielded a significant PFS improvement, with a hazard ratio for progression of 0.35 (95% CI, 0.21 to 0.57; P < .001) in the experimental versus control arm. CONCLUSION: The trial reached its primary end point of biochemical control and PFS, suggesting a clinical advantage for SBRT in addition to first-line AAP treatment in patients with metastatic castration-resistant prostate cancer.

Desensitization Protocol for Cemiplimab-Related Infusion Reaction in Cutaneous Squamous Cell Carcinoma: A Case Report and Literature Review.

BACKGROUND: The landscape of systemic therapies for advanced non-melanoma skin cancers has been revolutionized by the advent of immunotherapy. Cemiplimab is the only immune checkpoint inhibitor (ICI) approved by the European Medicine Agency for recurrent/metastatic cutaneous squamous cell carcinoma (cSCC). Its excellent efficacy outcomes are achieved due to its good tolerability profile. The drug-related hypersensitivity reaction (HSR) is a well-known issue in oncology, but it is rarely reported in respect to immune checkpoint inhibitors. Cemiplimab is among the agents with the best infusion tolerability profiles. Clinical practice guidelines in this field are lacking. RESULTS: We report on the successful management of a severe infusion reaction induced by Cemiplimab in a patient with cSCC based on a desensitization protocol, which led to adequate treatment delivery and prolonged clinical benefit. A review of the available literature on HSR rates and its management with ICIs, and on drug desensitization (DD) protocols and their efficacy, was conducted to highlight the limited knowledge on this topic and its importance. CONCLUSION: Our experience highlights the need for a DD protocol in order to improve the treatment of HSRs, particularly when elicited by an immunotherapy agent, preventing treatment discontinuation and preserving its efficacy.

PSMA guided approach for bIoCHEmical relapse after prostatectomy- (PSICHE) trial (NCT05022914). Detection rate and treatment decision after 68Ga-PSMA PET/CT within a prospective study.

BACKGROUND: Ultrasensitive imaging has been demonstrated to influence biochemical relapse treatment. PSICHE is a multicentric prospective study, aimed at exploring detection rate with 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and outcomes with a predefined treatment algorithm tailored to the imaging. METHODS: Patients affected by biochemical recurrence after surgery (prostate specific antigen [PSA] > 0.2 < 1 ng/mL) underwent staging with 68Ga-PSMA PET/CT. Management followed this treatment algorithm accordingly with PSMA results: prostate bed salvage radiotherapy (SRT) if negative or positive within prostate bed, stereotactic body radiotherapy (SBRT) if pelvic nodal recurrences or oligometastatic disease, androgen deprivation therapy (ADT) if nonoligometastatic disease. Chi-square test was used to evaluate the relationship between baseline features and rate of positive PSMA PET/CT. RESULTS: One hundred patients were enrolled. PSMA results were negative/positive in the prostate bed in 72 patients, pelvic nodal or extrapelvic metastatic disease were detected in 23 and 5 patients. Twenty-one patients underwent observation because of prior postoperative radiotherapy (RT)/treatment refusal. Fifty patients were treated with prostate bed SRT, 23 patients underwent SBRT to pelvic nodal disease, five patients were treated with SBRT to oligometastatic disease. One patient underwent ADT. NCCN high-risk features, stage > pT3 and ISUP score >3 reported a significantly higher rate of positive PSMA PET/CT after restaging (p = 0.01, p = 0.02, and p = 0.002). By quartiles of PSA, rate of positive PSMA PET/CT was 26.9% (>0.2; <0.29 ng/mL), 24% (>0.3; <0.37 ng/mL), 26.9% (>0.38; <0.51 ng/mL), and 34.7% (>0. 52; <0.98 ng/mL). CONCLUSIONS: PSICHE trial constitute a useful platform to collect data within a clinical framework where modern imaging and metastasis-directed therapy are integrated.

Equity, Diversity, and Inclusion in Radiation Oncology: A Bibliometric Analysis and Critical Review.

The promotion of equity, diversity, and inclusion (EDI) is being increasingly pursued in health care, both in general and within radiation oncology. Because bibliometrics is a powerful tool to reveal the scientific literature on a specific topic during a certain timespan, a systematic bibliometric analysis of the documents published on EDI in radiation oncology was performed, aiming at exploring common patterns in research and emerging trends, tracking collaborations and networks, and anticipating future directions in clinical research. Standard descriptive statistics and bibliometric techniques were used in the analysis. A collaboration network and thematic map were generated from the data. Four domains were represented: (1) motor themes, including themes well developed and important for the structuring of the research field; (2) niche themes, representing the isolated topics that do not share important external links with other themes; (3) emerging themes, referring to still weakly developed topics; and (4) basic themes, including the essential topics. EDI in the profession of radiation oncology is essential to ensure that the workforce delivering radiation oncology care both draws from the full talent pool of human capital and delivers the highest quality science and clinical care to all patients. The burgeoning literature on EDI in radiation oncology suggests that a large and growing cohort of scholars within radiation oncology are dedicated to addressing these important challenges.

Predictive factors for tolerance to taxane based chemotherapy in older adults affected by metastatic prostate cancer (ANCHISES-NCT05471427): A prospective observational trial including patients with metastatic hormone sensitive and castrate resistant prostate cancer treated with taxane chemotherapy.

INTRODUCTION: Taxane-based chemotherapy is one of the main cornerstones for treatment of metastatic prostate cancer (mPCa). In aged and well-fit patients, an indication for taxane chemotherapy should remain similar to the general population. Aiming to explore predictive factors of fitness to taxane chemotherapy in older adult patients, a prospective observational study was carried out in our institution. MATERIALS AND METHODS: We collected data from a prospective mono-centric database of patients aged ≥70 years old that were treated in our department. All patients underwent taxane treatment (either docetaxel or cabazitaxel, the latter only in second line setting) starting with standard treatment schedules (75 mg/m2 or 25 mg/m2 every three weeks, respectively). Data about G8 score post treatment decreases were collected and reported. We explored associations between baseline age, G8 score, and Charlson Comorbidity Index (CCI) with taxane dose reduction (DR), treatment temporary suspension (TS), or definitive interruption (TDI). Logistic regression analysis was performed to explore potential predictive factors for tolerability in patients treated with docetaxel. RESULTS: One hundred-eighteen patients underwent taxane chemotherapy between 2011 and 2022, the majority of cases in metastatic castrate resistant prostate cancer (mCRPC) setting (85.6%). In the overall population, DR was performed in 40.7% of cases, and TS and TDI were deemed necessary in 28% and 22.9% of patients, respectively. Forty-seven percent of patients reported a significant deterioration in terms of G8 score (from > to ≤14). Sixty-two percent of the overall population were deemed fit for further treatment after taxane chemotherapy. Rate of DR, TS, and TDI was 29.4%, 11.8% and 9.2% in the docetaxel subgroup, vs 48%, 60% and 12% of patients treated with cabazitaxel, respectively. Lower baseline G8 was reported as a continuous variable and the only independent predictive factor for TDI in docetaxel subgroup (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.25-0.68, p = 0.0008). DISCUSSION: Our data suggest that tolerability of taxane regimens in a pre-treated population of older patients with prostate cancer is acceptable, despite a non-negligible rate of TDI. Taxane chemotherapy should not be denied a priori in order to avoid undertreatment of older adult patients.

The impact of patient preference in the treatment algorithm for recurrent/metastatic head and neck squamous cell carcinoma.

The advent of immune checkpoint inhibitors for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) has revolutionized the standard of care approach in first-line treatment. The heterogeneity of disease presentation and treatment-related toxicities can be associated with suboptimal patient compliance to oncologic care. Hence, prioritizing quality of life and well-being are crucial aspects to be considered in tailoring the best treatment choice. The aim of our work is to present a short report on the topic of the patient's preference in regard to treatment and its consequences on quality of life in the recurrent/metastatic setting. According to the literature, there's an unmet need on how to assess patient attitude in respect to the choice of treatment. In view of the availability of different therapeutic strategies in first-line management of RM-HNSCC, increasing emphasis should be put on integrating patient preferences into the medical decision-making.

A narrative review of postoperative adjuvant radiotherapy for non-small cell lung cancer.

Objective: To summarize the principal studies investigating the role of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) and to discuss the recent major breakthroughs deriving from the Lung ART trial, in order to provide a real-world scenario of the management of resected NSCLC patients. Background: Surgery followed by platinum-based chemotherapy remains the mainstay of adjuvant treatments for completely resected stage II and IIIA NSCLC. Less consistent is the employment of PORT, as no significant benefit was clearly identified from the previous published meta-analysis. Furthermore, the recent results of Lung ART trial questioned for the first time the efficacy of PORT for pathological N2 (pN2) NSCLC patients. Hence, the need to define if PORT still has a role for resected NSCLC and which subgroup of patients could benefit most from this treatment. Methods: A literature search of PubMed was performed to identify publications, including prospective and retrospective clinical studies, meta-analysis and systematic review of PORT for NSCLC. No limit concerning years of publication or publication status were applied. Only papers using the English language were selected. The ESMO 2020 and ESMO 2021 online resources were used to analyze the Lung ART trial results. The authors provide a narrative summary of the findings and implications of these studies and how they improve the clinical practice. Conclusions: PORT was considered the standard of care for patients with completely resected pN2 NSCLC based on the results of an old meta-analysis that did not demonstrate a detrimental effect. The more recent randomized phase III Lung ART trial concluded that PORT could not anymore be recommended for pN2 NSCLC as a significant benefit in terms of 3 years disease-free survival (DFS) was not reached and an increased rate of radiotherapy related toxicity was observed. Retrospective studies suggest a possible role of PORT for incompletely resected NSCLC patients and those with an extranodal extension (ENE), but this issue needs to be reinforced from randomized prospective trials. The extensive publication of Lung ART trial is largely awaited to define if there is a role of PORT for resected NSCLC patients.

Quitting Smoking At or Around Diagnosis Improves the Overall Survival of Lung Cancer Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Lung cancer (LC) remains a disease with poor prognosis despite recent advances in treatments. Here, we aimed at summarizing the current scientific evidence on whether quitting smoking at or around diagnosis has a beneficial effect on the survival of LC patients. METHODS: We searched MEDLINE and EMBASE for articles published until 31st October, 2021, that quantified the impact on LC patients' survival of quitting smoking at or around diagnosis or during treatment. Study-specific data were pooled into summary relative risk (SRR) and corresponding 95% confidence intervals (CI) using random effect meta-analysis models. RESULTS: Twenty-one articles published between 1980 and 2021 were included, which encompassed a total of over 10,000 LC patients. There was substantial variability across studies in terms of design, patients' characteristics, treatments received, criteria used to define smoking status (quitters or continued), and duration of follow-up. Quitting smoking at or around diagnosis was significantly associated with improved overall survival (SRR 0.71, 95% CI 0.64-0.80), consistently among patients with non-small cell LC (SRR 0.77, 95% CI 0.66-0.90, n studies = 8), small cell LC (SRR 0.75, 95% CI 0.57-0.99, n studies = 4), or LC of both or unspecified histological type (SRR 0.81, 95% CI 0.68-0.96, n studies = 6). CONCLUSIONS: Quitting smoking at or around diagnosis is associated with a beneficial effect on the survival of LC patients. Treating physicians should educate LC patients about the benefits of quitting smoking even after diagnosis and provide them with the necessary smoking cessation support.

Steroid Use Independently Predicts for Poor Outcomes in Patients With Advanced NSCLC and High PD-L1 Expression Receiving First-Line Pembrolizumab Monotherapy.

BACKGROUND: Real-world data have suggested a detrimental effect of steroid use in patients with advanced non-small-cell lung cancer (NSCLC) receiving immunotherapy. However, previous studies included heterogeneous cohorts of patients receiving different lines of treatment with several immuno-oncology agents and various combinations of chemotherapy and immuno-oncology agents. PATIENTS AND METHODS: A comprehensive clinicopathologic database of patients with NSCLC and programmed cell death ligand 1 >50% treated with frontline pembrolizumab monotherapy was constructed in 14 centers in Italy, Spain, Greece, and Switzerland. A multivariate analysis adjusting for the established prognostic factors was performed using a Cox regression model. RESULTS: For the 265 eligible patients, the median age at diagnosis was 67 years, 66% were male, 90% were current or former smokers, 18% had had an Eastern Cooperative Oncology Group performance status of 2 or 3. Of the NSCLC subtypes, 64% were adenocarcinoma and 25% were squamous cell. Of the patients, 18% had had brain metastases at diagnosis and 24% had received steroids before or during pembrolizumab treatment. The median time to progression was 4.4 months with and 13.7 months without steroid use (hazard ratio [HR], 2.55; 95% confidence interval [CI], 1.69-3.85; log-rank P < .001). The median survival was 22.5 months for the whole cohort, 7.7 months for the steroid group, and not reached for the non-steroid group (HR, 3.64; 95% CI, 2.34-5.68; log-rank P < .001). On multivariate analysis accounting for all established prognostic variables, steroid use was still independently associated with a high risk of progression (HR, 1.864; 95% CI, 1.179-2.949; P = .008) and death (HR, 2.292; 95% CI, 1.441-3.644; P < .001) CONCLUSIONS: In patients with advanced NSCLC and programmed cell death ligand 1 expression > 50% receiving frontline pembrolizumab monotherapy, any use of steroids before or during treatment was associated with an 86% increase in the risk of progression and a 2.3-fold increase in the risk of death, even accounting for palliative indication-related bias, including the presence of central nervous system metastasis. The use of steroids for palliative indications should be restricted to absolutely necessary for patients receiving immuno-oncology monotherapy.

Real-World Treatment Patterns and Survival Outcome in Advanced Anaplastic Lymphoma Kinase (ALK) Rearranged Non-Small-Cell Lung Cancer Patients.

Introduction: Survival of ALK-rearranged NSCLC patients has dramatically improved by the use of multiple ALK-tyrosine kinase inhibitors (ALK-TKI). However, still little is known about the impact of drug sequencing and clinical features on survival in a real-world setting. Methods: Patients with stage IV ALK-rearranged NSCLC treated at six centers in Switzerland and Italy were identified and standard clinical variables collected. OS curves were constructed using the Kaplan-Meier method and compared with the log-rank test. Multivariate Cox proportional hazard analysis was applied to determine the correlations between clinical features and OS. In four patients, biopsies were subjected to NGS. Results: One-hundred and twenty-one patients with stage IV ALK-rearranged NSCLC diagnosed between 2011 and 2016 were included. With a median follow-up time of 39.5 months, the median OS from diagnosis of stage IV disease was 48.0 months. First-line treatment consisted of an ALK-TKI in 24% of patients, with crizotinib in 83% of them. Chemotherapy as first-line treatment did not influence OS (p = 0.955). The use of more than one ALK-TKI line positively correlated with OS (p = 0.016), as well as the use of alectinib or lorlatinib in any treatment line, as compared to the use of crizotinib ± ceritinib (p = 0.022). A never smoking history was an independent prognostic factor for OS (p = 0.032). Moreover, treatment with alectinib significantly improved OS. Conclusions: Targeted treatment for ALK-positive NSCLC patients lead to prolonged OS. Smoking status was a negative independent prognostic factor in a multi-variate analysis. The use of alectinib or lorlatinib in any treatment line improved overall outcome.

Neutrophil-to-lymphocyte ratio in combination with PD-L1 or lactate dehydrogenase as biomarkers for high PD-L1 non-small cell lung cancer treated with first-line pembrolizumab.

The identification of prognostic and predictive biomarkers for high-programmed cell death-ligand 1 (PD-L1) advanced non-small cell lung cancer (aNSCLC) treated with first-line pembrolizumab could support the decision-making about possible combination therapies. To explore the baseline neutrophil-to-lymphocyte ratio (NLR) with the possible addition of PD-L1 tumour proportion score (TPS) level or lactate dehydrogenase (LDH) as possible prognostic biomarkers by a multicenter retrospective exploratory analysis aiming at identifying favourable-risk patients. Baseline NLR was available for all 132 high PD-L1 aNSCLC patients, PD-L1 level and LDH for 81 (61%) and 85 (64%) patients, respectively. NLR, PD-L1 and LDH cut-offs by receiver operating characteristic (ROC) curves were 4.9, 77.5% and 268.5, respectively. Seventy-one patients (54%) had NLR <5; 25 out of 81 NLR <5 (31%) had PD-L1 >80%, 26 out of 85 (31%) NLR <5 and normal LDH (nLDH). Median follow-up was 16.3 months. As compared to NLR >5, significantly better 2-year overall survival (OS) and progression-free survival (PFS) were observed with NLR <5 [62% vs. 41%, P=0.005, hazard ratio (HR) 0.45, and median of 12.0 vs. 5.7 months, P=0.01, HR 0.56, respectively], NLR <5 + PD-L1 >80% (81%, P=0.006, HR 0.20 and median of 14.7, P=0.03, HR 0.44, respectively), and NLR <5 + nLDH (74%, P=0.009, HR 0.25 and median of 14.7, P=0.02, HR 0.40, respectively). NLR <5 and NLR <5 + nLDH significantly associated with PD (P=0.008 and P=0.025, respectively) but not response rate (RR) (P=0.09 and P=0.07, respectively); NLR <5 + PD-L1 >80% both RR (P=0.03) and PD (P=0.02). NLR <5 ± PD-L1 >80% or nLDH could represent easy-to-assess tools to identify high PD-L1 aNSCLC patients with favourable outcome following first-line pembrolizumab monotherapy.

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab.

Objectives: We retrospectively analysed patients with advanced non-small-cell lung cancer (NSCLC) harbouring high PD-L1 expression (>50%) and treated with front-line pembrolizumab, comparing outcomes of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to those with PS 0-1.Methods: Data were collected by 16 participating centres. All patients with NSCLC and high PD-L1, treated with first-line pembrolizumab were included. We collected medical data from patient files, pathology and laboratory reports. Patient characteristics, comorbidities, PS, and tumour characteristics were reported. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were calculated.Results: 302 patients were included, 246 with PS 0-1, 56 with PS 2. RR was 72% among patients with PS 0-1 compared to 45% with PS2 (odds ratio (OR) 0.31 (95% CI: 0.17-0.57), p < .001). Median PFS was 2.6 months (95% CI: 1.9-5.1) among patients with PS2 and 11.3 months (95% CI: 8.5-14.4) among those with PS 0-1. Median OS was 7.8 months (95% CI: 2.5-10.7) in the PS2 group, not reached in the PS 0-1 group. PS 2 remained predictive of poor outcomes in multivariate analysis.Conclusion: PS 2 is a strong independent predictor of poor response and survival in NSCLC patients with high PD-L1, treated with front-line pembrolizumab. Prospective randomised trials comparing immunotherapy to chemotherapy in this population would be welcome.

Outcomes from salvage chemotherapy or pembrolizumab beyond progression with or without local ablative therapies for advanced non-small cell lung cancers with PD-L1 ≥50% who progress on first-line immunotherapy: real-world data from a European cohort.

BACKGROUND: In this real-world multicenter study we addressed the activity of post-progression anticancer treatments after first-line pembrolizumab in advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥50%. METHODS: Clinico-pathological data of PD-L1 ≥50% advanced NSCLCs who failed first-line pembrolizumab were collected in 14 Oncologic Centers from different European countries. Types of subsequent anticancer treatment and outcomes on salvage chemotherapy or pembrolizumab beyond progression with or without the addition of local ablative therapies were reported. RESULTS: Out of 173 patients, 100 had progressed on pembrolizumab, of which 60 patients (60%) met eligibility criteria and were treated with either salvage chemotherapy (42/60, 70%) or pembrolizumab beyond progression (18/60, 30%). Overall, median age was 66 years, 63.3% were male, 60.0% had a performance status of 0-1, 88.3% were smokers and 61.7% had adenocarcinoma histology. In patients evaluable for response, objective response rate to salvage chemotherapy was 41.9%, with no significant difference according to the type of regimen (42.9% for platinum-based and 40.0% for single-agent chemotherapy). Median progression-free survival (PFS) to salvage chemotherapy was 4.5 months. Among patients treated with pembrolizumab beyond progression, 13 out of 18 patients (72.2%) had progressive disease in ≤2 organ sites, of whom 9 (69.2%) were managed with the addition of local ablative therapies consisting of radiation at progressive lesion(s). No significant difference was noted in terms of post-progression survival between the salvage chemotherapy and the pembrolizumab beyond progression groups of patients (6.9 versus 8.1 months, respectively, P=0.08). CONCLUSIONS: In PD-L1 ≥50% advanced NSCLCs who progress on first-line pembrolizumab, salvage chemotherapy is associated with a remarkable anticancer activity, while select patients may benefit from continuation of pembrolizumab beyond progression, with the possible addition of local ablative radiotherapy in oligoprogressive cases.