Lorlatinib experience in a patient with ALK + non-small cell lung cancer on hemodialysis: A case report.

INTRODUCTION: Lorlatinib is a potent third-generation anaplastic lymphoma kinase/c-ros oncogene 1 (ALK)/ROS1 oral tyrosine kinase inhibitor that has broad coverage of acquired resistance mutations and is currently indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ALK-positive. CASE REPORT: In this case, we aimed to present the safety and effectiveness of lorlatinib use in a patient diagnosed with ALK-positive metastatic NSCLC who underwent hemodialysis 3 days a week. MANAGEMENT & OUTCOME: A 76-year-old female patient has been undergoing regular hemodialysis for about 2 years. A brain magnetic resonance imaging (MRI) was taken due to headache and a mass was detected. She was diagnosed with lung adenocarcinoma as a result of excisional biopsy. Positron emission tomography/ computed tomography (PET/CT) showed a mass in the hilar region of the left lung and multiple lymphadenopathy in the mediastinum. In February 2023, 100 mg lorlatinib was started daily. There was no significant regression in PET-CT and no brain MRI residue during follow-up. The patient has been continuing lorlatinib for approximately 1 year with almost complete response, with no side effects other than hypercholesterolemia. DISCUSSION: We presented our experience using lorlatinib in a patient with metastatic ALK + NSCLC undergoing hemodialysis. Although the dosage of lorlatinib in hemodialysis patients is still controversial, our case report indicates that 100 mg lorlatinib was safe in this patient.

Survival trends among patients with metastatic non-small cell lung cancer before and after the approval of immunotherapy in the United States: A Surveillance, Epidemiology, and End Results database-based study.

BACKGROUND: In 2015, the US Food and Drug Administration approved nivolumab as the first immunotherapy for patients with advanced non-small cell lung cancer (NSCLC). However, population-based survival benefit studies after the introduction of immunotherapy in lung cancer are lacking. This study examined overall survival (OS) and cancer-specific survival in patients with NSCLC in the pre immunotherapy and immunotherapy eras. METHODS: This study used the Surveillance, Epidemiology, and End Results database, which spanned 17 registries from 2000 to 2020. Two cohorts were delineated: preimmunotherapy (2010-2014) and immunotherapy (2015-2020), which coincided with nivolumab's approval. RESULTS: This study included 191,802 patients, 90,807 in the preimmunotherapy era and 100,995 in the immunotherapy era. OS was significantly higher in the immunotherapy era, as shown by Kaplan-Meier curves (1-year OS, 40.1% vs. 33.5%; 3-year OS, 17.8% vs. 11.7%; 5-year OS, 10.7% vs. 6.8%; median OS, 8 vs. 7 months; p < .001 by log-rank test). Similarly, cancer-specific survival improved in the immunotherapy era (1-year survival, 44.0% vs. 36.8%; 3-year survival, 21.7% vs. 14.4%; 5-year survival, 14.3% vs. 9.0%; median OS, 10 vs. 8 months; p < .001 by log-rank test). Survival rates were significantly better in the immunotherapy era, as confirmed by multivariate analysis with a Cox proportional hazards model after adjusting for age, sex, race, income, and geographical area (adjusted hazard ratio, 0.830; 95% CI, 0.821-0.840; p < .001). CONCLUSIONS: In summary, the survival rate of patients with metastatic NSCLC has improved since the introduction of immunotherapy.

Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy.

INTRODUCTION: For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3­DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population. METHODS: This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart). RESULTS: In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%. CONCLUSION: The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.

The Interplay of Malignancy and Endocarditis: A Report of a Rare Case of Marantic Endocarditis in Metastatic Lung Adenocarcinoma.

Endocarditis involves inflammation of the inner layer of the heart, known as the endocardium. This condition typically presents with vegetation, with bacteria and fungi usually being the primary culprits. It is divided into two main categories based on its cause: infectious endocarditis and noninfectious endocarditis (NIE). Most cases of NIE are associated with malignancies, most of which are adenocarcinomas of the pancreas and lungs. We present the case of a 63-year-old man with recently diagnosed stage 3 non-small cell lung cancer and a previous history of thrombosis to the renal and popliteal arteries alongside an extensive cardiovascular history who presented with blurry vision secondary to multiple acute ischemic strokes, initially thought to be a consequence of septic emboli due to bacterial endocarditis; however, further workup revealed otherwise, illustrating the complex relationship between malignancy and endocarditis and its ramification.

Palliative care integration and end-of-life care intensity for patients with NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) without oncogenic driver mutations is considered to have a poor prognosis, although recent therapeutic progress. This study aims to assess the real-life integration of palliative care (PC) and the intensity of end-of-life (EOL) care for this population. METHODS: This was an observational cohort study of decedent patients from metastatic NSCLC without oncogenic driver mutations over the period 01/2018 to 12/2022, treated in first line with immunotherapy +/- chemotherapy. We analysed PC integration and aggressiveness criteria of EOL care in the last month before death: systemic anti-cancer treatment administration, emergency room visits, intensive care unit admission, hospitalization, hospitalization duration > 14 days, and hospital death. RESULTS: Among 149 patients, 75 (50 %) met the PC team at least once, and the median time from the first encounter to death was 2.3 months. In the last month before death, at least one criterion of aggressive EOL care was present for 97 patients (70 %). For patients with PC use < 30 days and for patients with PC use < 90 days before death, there were significant changes: increase in the frequency of systemic anti-cancer treatment (respectively 51.1 % vs 20 %; p < 0.001 and 58.7 % vs 6.2 %; p < 0.001); decrease in hospitalization lasting > 14 days (respectively 30 % vs 7 %; p = 0.001 and 36 % vs 6.2 %; p = 0.018) and in death hospitalisation (respectively 66 % and 18 %; p < 0.001 and 58.7 % and 10.3 %; p < 0.001). After adjusting for the factors tested, patients with no PC or late PC use in the last month before death or in the last three month before death, the odds ratio (OR) remained significantly greater than 1 (respectively OR = 3.97 [1.70; 9.98]; p = 0.001 and OR = 23.1 [5.21-177.0], p < 0.0001). CONCLUSION: PC is still insufficiently integrated for patients with NSCL cancer. Cancer centres should monitor key indicators such as PC use and aggressiveness criteria of EOL care.

Jaundice and Higher Procalcitonin Level Revealing a Small-Cell Lung Cancer With Pancreatic Metastasis: A Case Report From Eastern Morocco.

Small-cell lung cancer (SCLC) is highly aggressive, with a severe tendency for metastasis. Pancreatic metastasis in SCLC is uncommon, also jaundice as a major symptom of small-cell lung cancer is even rarer. The diagnosis of pancreatic metastasis is a real challenge for the medical team, it relies on both radiological and pathological details. We report a case of a 58-year-old male admitted for SCLC with pancreatic metastasis and a higher level of procalcitonin. He received platinum-based chemotherapy with a swell response. The focus of this study will be on the characteristics of pancreatic metastasis, along with their diagnosis and treatment approaches. Procalcitonin as a paraneoplastic syndrome will also be discussed in this study.

Coexistence of Lung Cancer and Neurocysticercosis: A Rare Case.

Lung cancer with brain metastasis has a high morbidity and mortality worldwide. Neurocysticercosis is a parasitic infection commonly found in regions with poor sanitation. We present a case with the coexistence of lung cancer and neurocysticercosis. A 57-year-old Caucasian female, with a history of secondhand smoke exposure, presented with a cough. Further evaluation revealed a lesion in the right upper lobe of the lung on a CT scan, a frontal lobe lesion on brain MRI, and hypermetabolic lymph nodes on a PET scan. Biopsies confirmed invasive moderately differentiated adenocarcinoma, indicating stage 4 lung cancer with a solitary brain metastasis. The patient underwent stereotactic radiosurgery for the brain lesion and subsequently received chemoradiation therapy. Upon completion of therapy, the patient showed improvement in both lung and brain lesions. Durvalumab maintenance therapy was initiated. However, a follow-up MRI of the brain revealed a new lesion in the right lateral ventricle. Stereotactic radiosurgery was performed to target this lesion. Five months later, a repeat MRI showed growth of the brain lesion. Given the atypical image finding, a biopsy of the right lateral ventricle lesion was performed, revealing an unexpected diagnosis of calcified parenchymal neurocysticercosis. The patient was referred to an infectious disease specialist who started the patient on dexamethasone without antiparasitic treatment. The co-occurrence of metastatic lung cancer to the brain and neurocysticercosis presents significant diagnostic and therapeutic complexities. Despite stereotactic radiosurgery, the patient's neurologic symptoms failed to improve, and subsequent radiographic assessments yielded inconclusive results. Consequently, a brain biopsy was performed, deviating from the usual practice in cancer management, revealing the unexpected presence of neurocysticercosis. This unforeseen diagnosis underscores the critical significance of contemplating alternative etiologies in patients exhibiting atypical clinical manifestations, particularly in regions devoid of prevalent parasitic infections. This case highlights the challenges in identifying and managing complex cases involving lung cancer and neurocysticercosis, where treatment decisions must balance the need for oncologic control and the management of parasitic infection.

Leptomeningeal Metastasis: A Rare Complication of Non-small Cell Lung Cancer.

Leptomeningeal metastasis (LMM) is a rare complication of non-small cell lung cancer (NSCLC) that can present with a range of neurological symptoms depending on the site(s) of metastatic involvement. We present a case of a 54-year-old woman who was initially diagnosed with suspected inflammatory neuritis secondary to a known systemic lupus erythematosus (SLE) diagnosis after presenting with multiple months of progressive neuro-ophthalmologic symptoms; however, she was eventually diagnosed with LMM secondary to a previously undiagnosed NSCLC. This case both underscores the challenges of diagnosing LMM due to its nonspecific presentation, as well as highlights the importance of including LMM in the differential diagnosis for patients presenting with vague neurological symptoms in the context of another inflammatory disease process.

A Case of MRI-Negative Leptomeningeal Disease From Non-small Cell Lung Cancer.

Leptomeningeal disease (LMD) is a rare complication of advanced non-small cell lung cancer (NSCLC), associated with a poor prognosis. We report the case of a 55-year-old man, who presented with a metastatic NSCLC with limited brain and abdominal metastases. He was treated with both chemoimmunotherapy and stereotactic radiotherapy (SRT) to the brain. Despite treatment, the patient experienced progressive neurological symptoms not in keeping with the extent of disease seen on imaging of the brain. Due to this incongruence between symptoms and radiologic findings, he underwent a lumbar puncture, which had positive cytology for LMD. He had a rapid progression of symptoms and died six days after the discovery of LMD. We review the available literature regarding the prevalence of MRI-negative LMD from a solid primary malignancy.

Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment: A phase 2 clinical trial (BG01-1801).

Background: Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), but acquired resistance presents challenges. The aim of this open-label, multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone, a novel genetically engineered epothilone analog and microtubule-stabilizing agent, as a third- or later-line treatment for locally advanced or metastatic NSCLC. Methods: Patients who had failed standard second-line treatment (including platinum-containing chemotherapy or targeted therapy) received utidelone (40 mg/m2 via intravenous injection daily, day 1-5) every 21 days. The primary endpoint was the objective response rate (ORR). Secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: From March 12, 2019 to January 18, 2021, 26 pretreated patients with locally advanced or metastatic NSCLC (100% of patients had received prior platinum and 65.4% patients had received prior taxane treatment) were enrolled (80.8% of patients had adenocarcinoma). At baseline, nine (34.6%) patients had received second-line treatment, 10 (38.5%) patients had received third-line treatment, and seven (26.9%) patients had received fourth- or later-line treatment. By the data cut-off date of August 10, 2021, the median follow-up was 7.49 months (range, 1.4-26.7 months). The ORR was 15.4% (95% confidence interval [CI], 4.4%-34.9%) in the intention-to-treat (ITT) cohort (N = 26) and 19.0% (95% CI, 5.4%-41.9%) in the per-protocol (PP) cohort (N = 21). The disease control rate was 69.2% (95% CI, 48.2%-85.7%) and 81.0% (95% CI, 58.1%-94.6%) in the ITT and PP cohorts, respectively. The median DoR was 4.1 months (95% CI, 3.1-5.1 months) in the ITT cohort. The median PFS was 4.37 months (95% CI, 2.50-5.29 months) in the ITT cohort and 4.37 months (95% CI, 2.50-9.76 months) in the PP cohort. The median OS was not reached, and the 12-month OS rate was 69% (95% CI, 45.1%-84.1%). Grade 3/4 treatment-emergent adverse events occurred in 38.5% of patients, and the most common was peripheral neuropathy (23.1%, all Grade 3), which was manageable with dose modifications. Conclusions: In this clinical trial, utidelone showed promising efficacy and had a manageable safety profile. Further clinical studies are warranted to confirm its role in NSCLC treatment. Trial registration: No.NCT03693547; https://classic.clinicaltrials.gov.

Molecular Diagnostics and Treatment Patterns in Metastatic Non-small Cell Lung Cancer Patients: Real World Evidence from Greece: LACHESIS Study.

BACKGROUND/AIM: Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer deaths globally. In Greece in 2020, 8,960 new cases were reported. NSCLC's 5-year survival rates range from 54% (stage I) to less than 2% (stage IV); however, innovative therapies like immune check points inhibitors (ICIs) and targeted treatments have notably enhanced outcomes. The aim of this study was to assess the 1st and 2nd line treatment patterns with the introduction of new treatment modalities. Additionally, we evaluated biomarker testing approaches in NSCLC. PATIENTS AND METHODS: LACHESIS was a retrospective multinational study, collecting and analyzing data from adult patients from Russia, Bulgaria, and Greece with metastatic NSCLC either newly diagnosed or relapsed from earlier stages, who had the option to undergo biomarker testing (genetic alterations/programmed death-ligand 1 protein expression levels, PD-L1), and who received 1st line treatment for squamous (SQ) or non-squamous (N-SQ) NSCLC. Subsequent lines of therapy were also reported. RESULTS: The Greek site registered retrospective data from 250 NSCLC patients, of whom 206 were newly diagnosed (ND) metastatic NSCLC patients and 44 were patients relapsed from earlier stages. Seventy-two had SQ NSCLC and 169 had N-SQ NSCLC. For these patients, treatment patterns including immunotherapy±chemotherapy combinations were recorded. Biomarker testing patterns, including genetic alterations and PD-L1 expression levels were also documented. CONCLUSION: LACHESIS provides treatment patterns and biomarker testing data. Greek patients were treated according to international guidelines, with immunotherapy as a viable option, particularly for PD-L1 levels over 50%. Biomarker testing, crucial for non-squamous (N-SQ) cases, should yield timely results for driver mutations, prioritizing patient benefits.

Combination tumor-treating fields treatment for patients with metastatic non-small cell lung cancer: A cost-effectiveness analysis.

BACKGROUND: Tumor-treating field (TTFields) was a novel antitumor therapy that provided significant survival for previously treated metastatic non-small cell lung cancer (mNSCLC). The consistency of the cost of the new treatment regimen with its efficacy was the main objective of the study. METHODS: The primary parameters, derived from the Phase 3 LUNAR study, were collected to evaluate the cost and efficacy of TTFields plus standard-of-care (SOC) (immune checkpoint inhibitors [ICIs] and docetaxel [DTX]) or SOC in patients with mNSCLC by establishing a three-state Markov model over a 15-year time horizon. Primary outcome measures for this study included costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed. RESULTS: The total costs of TTFields plus SOC, TTFields plus ICI, and TTFields plus DTX were $319,358, $338,688, and $298,477, generating 1.23 QALYs, 1.58 QALYs, and 0.89 QALYs, respectively. The ICERs of TTFields plus SOC versus SOC, TTFields plus ICI versus ICI, and TTFields plus DTX versus DTX were $613,379/QALY, $387,542/QALY, and $1,359,559/QALY, respectively. At willingness-to-pay (WTP) thresholds of $150,000/QALY, the probability of combination TTFields being cost-effective was 0%. In addition, TTFields plus SOC exhibited similar efficacy (1.12 QALYs and 1.14 QALYs) and costs ($309,822 and $312,531) in the treatment of squamous cell carcinoma (SCC) and non-squamous cell carcinoma (NSCC) populations. CONCLUSIONS: In the United States, TTFields plus SOC as second-line treatment was not a more cost-effective strategy for patients with mNSCLC. Of the analyzed regimens, TTFields plus ICI was associated with most significant health benefits.

Clinical Benefit from Docetaxel +/- Ramucirumab Is Not Associated with Mutation Status in Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed on Platinum Doublets and Immunotherapy.

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/- ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/- ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20-14.80 m versus 8.40 m, 95% Cl: 7.12-9.68 m, LogRank P=0.019) than docetaxel +/- ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.

Diagnosis of Metastatic Non-Small Cell Lung Cancer during Hospitalization: Missed Opportunity for Optimal Supportive Care?

PURPOSE: The usual workup for patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) occurs in the ambulatory setting. A subset of patients present with acute care needs and receive the diagnosis while hospitalized. Palliative therapies are typically initiated when patients are outpatients, even when diagnoses are made when they are inpatients. Lengthy admission, rehabilitation needs after discharge, and readmissions are possible barriers to timely and adequate outpatient follow-up. The outcomes for these patients diagnosed in the hospital are not well characterized. We hypothesized that patients have been ill-served by current treatment patterns, as reflected by low rates of cancer-directed treatment and poor survival. PATIENTS AND METHODS: We performed a retrospective study of new inpatient diagnoses of metastatic NSCLC at our institution between 1 January 2012 and 1 January 2022. The primary outcome was the proportion of patients ultimately receiving cancer-directed therapy. Other outcomes included time to treatment, use of targeted therapy, palliative care/hospice utilization, and overall survival (OS). RESULTS: Seventy-three patients were included, with a median age of 57 years. Twenty-seven patients (37%) ultimately received systemic therapy with a median time from diagnosis to treatment of 37.5 days. Overall, 5.4% patients died while admitted, 6.8% were discharged to a hospice, 21.9% were discharged to a facility, and 61.6% were discharged home. Only 20 patients (27%) received palliative care consultation. The median OS for our entire population was 2.3 months, with estimated 6-month and 1-year OS rates of 32% and 22%, respectively. CONCLUSION: Patients with new inpatient diagnoses of metastatic NSCLC have extremely poor outcomes. Current management strategies resulted in few patients starting systemic therapy, yet most of the patients did not receive palliative care or hospice involvement. These findings demonstrate that there is a high unmet need to optimally support and palliate these patients.

First-line durvalumab in patients with PD-L1 positive, advanced non-small cell lung cancer (NSCLC) with a performance status of 2 (PS2). Primary analysis of the multicenter, single-arm phase II trial SAKK 19/17.

INTRODUCTION: The safety and efficacy of first-line durvalumab in PS2 patients with advanced NSCLC is unknown. Here, we present the primary analysis of first-line durvalumab in PS2 patients, unsuitable for combination chemotherapy. METHODS: In this single-arm, multicenter, phase II trial patients with PD-L1 positive (tumor proportional score ≥25%), advanced NSCLC with PS2, received four-weekly durvalumab 1500 mg. The primary endpoint was overall survival (OS) at 6 months. RESULTS: Forty-eight patients were included. Median follow-up was 23.3 months (95% CI: 14.3-28.6). OS at 6 months was 60% (95% CI: 45-74%). Median OS was 8.5 months (95%CI: 4.4-16.7). Objective response rate and median progression free survival were 17% (95% CI: 8-30%) and 2.5 months (95% CI: 1.8-7.1), respectively. Thirty-three deaths were observed at the time point of the analysis. Seven early fatal events considered not treatment-related occurred during the first 5 weeks of treatment. Four out of the first 7 early fatal events (4/7; 57%) were respiratory failure in patients with advanced symptomatic primary lung tumors. Three more early fatal events occurred after exclusion of patients with grade ≥ 3 dyspnea. Treatment-related AEs ≥G3 were reported in 9 patients (19%) and included colonic perforation in one patient (grade 5), colitis in 4 patients (8%), increased lipase in 3 patients (6%), and hepatitis in 2 patients (4%). CONCLUSIONS: First-line durvalumab in PS2 patients with advanced PD-L1 positive NSCLC results in a high number of early fatal events. When patients with grade ≥ 3 dyspnea are excluded a promising 6-month OS with an acceptable toxicity profile can be observed. Durvalumab could be an option instead of single agent chemotherapy for PS2 patients who are not candidates for platinum doublet chemotherapy provided they are well selected.

A retrospective analysis of optimal timing of thoracic radiotherapy for driver gene-negative metastatic non-small cell lung cancer.

BACKGROUND: The optimal timing of thoracic radiotherapy (TRT) in driver-gene-negative metastatic non-small cell lung cancer (mNSCLC) patients was retrospectively investigated based on survival and safety profile. METHODS: The efficacy and safety data of driver-gene-negative mNSCLC patients treated with TRT during maintenance after first-line therapy was collected. Patients whose primary tumor and metastatic lesions remained no progression during maintenance and then received TRT were categorized as the NP (no progression) group, while patients who experienced slow progression during maintenance without reaching progressive disease and then received TRT were categorized as the SP (slow progression) group. The efficacy and adverse events of TRT were analyzed. RESULTS: In total, 149 driver-gene-negative mNSCLC patients treated with TRT during maintenance were enrolled into the study, with 119 in the NP group and 30 in the SP group. After a median follow-up of 30.83 (range: 26.62-35.04) months, the median progression-free survival (PFS) in the NP group was 11.13 versus 9.53 months in the SP group (HR 0.599, p = 0.017). The median overall survival (OS) in the NP group was 32.27 versus 25.57 months in the SP group (HR 0.637, p = 0.088). The median PFS after radiotherapy (rPFS) was 6.33 versus 3.90 months (HR 0.288, p < 0.001). The adverse events were tolerable and manageable in both groups without significant difference (p > 0.05). CONCLUSION: The addition of TRT during the pre-emptive no progression phase was associated with a significantly longer PFS than during the delayed slow progression phase and had an acceptable safety profile. Our results might support the earlier initiation of TRT after induction therapy for some patients with driver-gene-negative mNSCLC.

The efficacy of immune checkpoint inhibitors following discontinuation for long-term response or toxicity in advanced or metastatic non-small-cell lung cancers: A retrospective study.

Background and Aims: The treatment of metastatic non-small-cell lung cancer (NSCLC) has been revolutionized by the arrival of immune checkpoint inhibitors (ICI). For patients without immune related adverse events (irAEs), it is recommended to continue the treatment as long as it provides clinical benefit or until unacceptable toxicity appears. The aim of our study was to evaluate survival data among patients with advanced or metastatic NSCLC following ICI discontinuation for reasons of long-term response or toxicity (irAEs). Methods: We included all patients with advanced or metastatic NSCLC treated with nivolumab and pembrolizumab at the Centre Jean Perrin, Clermont-Ferrand, France (January 1, 2016 to May 31, 2019). We focused on two groups in this study population: "Voluntary treatment discontinuation" (medical decision as a result of long-term response and patient decision) and "Treatment discontinuation due to toxicity" (irAEs). The primary endpoint was to evaluate the postdiscontinuation outcomes of these two groups: progression-free survival (PFS) and overall survival (OS), and rechallenge in the "voluntary discontinuation" group. Results: The final analysis concerned 146 patients, including 10 (7%) in the "discontinuation due to toxicity" group, 11 (8%) in the "voluntary discontinuation" group, 100 (68%) who discontinued treatment as a result of progression and 25 (17%) whose treatment was still on-going. The median PFS in the "discontinuation due to toxicity" group was not reached, and in the "voluntary discontinuation" group (n = 11) was 37 months (p = 0.4), versus 2 months in the progression group (p < 0.001). The median OS in "discontinuation due to toxicity," and in the "voluntary discontinuation" groups was not reached (p = 0.5), versus 10 months in the progression group (p < 0.001). Conclusion: Treatment discontinuation following long-term response to ICI treatment showed sustained response and long-term survival after discontinuation. The incidence of irAEs was associated with better long-term survival, even after ICI discontinuation.

Pembrolizumab Plus Chemotherapy Per PD-L1 Stratum In Patients With Metastatic Non-Small Cell Lung Cancer: Real-World Effectiveness Versus Trial Efficacy.

BACKGROUND: Clinical trial efficacy and real-world effectiveness of oncological treatments can differ. This study assessed the real-world survival outcomes of first-line pembrolizumab plus chemotherapy per PD-L1 stratum in patients with metastatic non-small cell lung cancer (mNSCLC) and compared them to clinical trial results. PATIENTS AND METHODS: All patients with nonsquamous and squamous mNSCLC who received first-line pembrolizumab plus chemotherapy in 7 Dutch teaching hospitals between January 1, 2019 and December 31, 2021 were included. Hazard ratios (HR) with confidence intervals (95% CI) for overall survival (OS) and progression-free survival (PFS) were estimated to determine the efficacy-effectiveness gap (EE gap) between real-world and clinical trial, stratified by PD-L1 stratum. RESULTS: The nonsquamous cohort (n = 486) consisted of 269 patients with PD-L1 < 1%, 158 with PD-L1 1% to 49%, and 59 with PD-L1 ≥ 50%. The squamous cohort (n = 117) consisted of 70 patients with PD-L1 < 1% and 47 with PD-L1 ≥ 1%. For OS, an EE gap was observed in nonsquamous patients with PD-L1 < 1% (HR 1.38 (95% CI 1.06-1.78; median OS 10 vs. 17.2 months) and HRs consistently >1 in all other nonsquamous and squamous PD-L1 strata, although not statistically significant. No EE-gap for PFS was observed in any stratum. CONCLUSION: No significant EE gap was found for pembrolizumab plus chemotherapy, except in the stratum nonsquamous mNSCLC with <1% PD-L1 tumor expression. In these patients, the survival in real-world was considerably shorter compared to the clinical trial results. Further studies are needed to determine which patient, treatment and or context factors contribute to this disparity.

Radioimmunotherapy With WT1 Dendritic Cell Vaccine for End-Stage Lung Adenocarcinoma Markedly Shrinks Tumors.

In advanced lung adenocarcinoma with metastases, the current standard of care does not in principle include aggressive cancer treatment with surgery and radiotherapy. Therefore, when chemotherapy cannot be continued, the patient is generally switched to palliative care. Our patient with stage IV lung adenocarcinoma in his 60s was receiving chemotherapy, which had to be discontinued due to severe side effects. As standard treatment was no longer indicated, he underwent radioimmunotherapy combined with WT1 dendritic cell vaccine therapy. As a result, the massive lung cancer shrank significantly and blood tests showed an improved immune profile. The growth of the lung cancer was suppressed, and the patient is completely symptom-free. After completing radioimmunotherapy, the patient continues to live a life similar to that of a healthy person. This case suggests that radioimmunotherapy can be useful as an active treatment in patients who are not eligible for standard treatment.

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON).

OBJECTIVES: In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs). PATIENTS AND METHODS: Treatment-naïve patients were randomized 1:1:1 to tremelimumab plus durvalumab and chemotherapy, durvalumab plus chemotherapy, or chemotherapy. PROs (prespecified secondary endpoints) were assessed using the European Organisation for Research and Treatment of Cancer 30-item core quality of life questionnaire version 3 (QLQ-C30) and its 13-item lung cancer module (QLQ-LC13). We analyzed time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization by log-rank test and improvement rates by logistic regression. RESULTS: 972/1013 (96 %) patients randomized completed baseline QLQ-C30 and QLQ-LC13 questionnaires, with scores comparable between treatment arms. Patients receiving tremelimumab plus durvalumab and chemotherapy versus chemotherapy had longer median TTD for all PRO items. Hazard ratios for TTD favored tremelimumab plus durvalumab and chemotherapy for all items except diarrhea; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, cognitive functioning, pain, nausea/vomiting, insomnia, constipation, hemoptysis, dyspnea, and pain in other parts. For durvalumab plus chemotherapy, median TTD was longer versus chemotherapy for all items except nausea/vomiting and diarrhea. Hazard ratios favored durvalumab plus chemotherapy for all items except appetite loss; 95 % confidence intervals did not cross 1.0 for global health status/QoL, physical functioning, role functioning, dyspnea, and pain in other parts. For both immunotherapy plus chemotherapy arms, improvement rates in all PRO items were numerically higher versus chemotherapy, with odds ratios > 1. CONCLUSIONS: Tremelimumab plus durvalumab and chemotherapy delayed deterioration in symptoms, functioning, and global health status/QoL compared with chemotherapy. Together with significant improvements in survival, these results support tremelimumab plus durvalumab and chemotherapy as a first-line treatment option in metastatic NSCLC.