Advanced Unresectable Non-small Cell Lung Research Articles

Draw on advantages and avoid disadvantages: CT-derived individualized radiomic signature for predicting chemo-radiotherapy sensitivity in unresectable advanced non-small cell lung cancer

BackgroundPresently, the options of concurrent chemo-radiotherapy (CCR) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) are controversial and there is no reliable prediction tool to stratify poor- and good-responders. Although radiomic analysis has provided new opportunities for personalized medicine in oncological practice, the repeatability and reproducibility of radiomic features are critical challenges that hinder their widespread clinical adoption. This study aimed to develop a qualitative radiomic signature based on the within-sample rank of radiomics features, and to use this novel method to predict CCR sensitivity in LA-NSCLC, avoiding the variability of quantitative signatures to multicenter effect.MethodsWe retrospectively analyzed 125 patients with stage III NSCLC who received treatment from our hospital. Radiomic features were extracted from pretreatment plain CT scans and constructed as feature pairs based on their within-sample rank. Fisher and univariate Cox analyses were performed to select feature pairs significantly associated with patients’ overall survival (OS). NSCLC-Radiomic (R422) cohort including 104 NSCLC patients was used as an independent testing cohort. NSCLC-Radiogenomic (RG211) cohort with matched RNA sequencing profiles, was used for functional enrichment analysis to reveal the underlying biological mechanism reflected by the signature.ResultsA qualitative signature, consisting of 15 radiomic feature pairs (termed as 15-RiFPS), was developed based on the Genetic Algorithm, which could optimally distinguish responder from non-responder with significantly improved OS if they received CCR treatment (log-rank P = 0.0009, HR = 13.79, 95% CIs 1.83–104.1). The performance of 15-RiFPS was validated in an independent public cohort (log-rank P = 0.0037, HR = 2.40, 95% CIs 1.30–4.40). Furthermore, the transcriptomic analyses provided biological pathways (‘glutathione metabolic process’, ‘cellular oxidant detoxification’) underlying the signature.ConclusionsWe developed a CT-derived 15-RiFPS, which could potentially help predict individualized therapeutic benefit of CCR in patients with LA-NSCLC. Additionally, we investigated the underlying intra-tumoral biological characteristics behind 15-RiFPS which would accelerate its clinical application. This approach could be applied to a wider range of treatments and cancer types.

Feasibility of induction chemoimmunotherapy (ID chemo-IO) followed by chemoradiation for locally advanced unresectable non-small cell lung cancer (NSCLC).

8071 Background: Data from the PACIFIC study demonstrated a 5-yr median progression free survival (PFS) and overall survival (OS) of 16.9 and 47.5 months respectively for patients with stage 3A and stage 3B NSCLC demonstrating a high risk of relapse. The 8th ed. of the IASLC staging project reports that the 60-month OS for stage 3A, B and C disease is 41%, 24% and 12% respectively, indicating that improved treatment options are needed for this patient population. Induction chemo-IO (ID chemo-IO) followed by concurrent chemo-radiation (CRT) has not been fully investigated due to concerns regarding the toxicity profile, but this may representant an important unexplored avenue for research. We aim to describe the outcomes of patients who received ID chemo-IO followed by CRT with or without maintenance IO. Methods: We conducted a retrospective study across all Mayo Clinic sites. Patients were included if they were diagnosed with Stage 3 NSCLC deemed ineligible for resection and/or requiring raditation over a large-field ] by a multidisciplinary team with plans for ID chemo-IO prior to CRT and maintenance IO. A total of 927 cases of stage 3 NSCLC patients were screened and those receiving ID chemo-IO followed by CRT were extracted (n = 36). Clinical endpoints are PFS, OS, overall response rate (ORR) and treatment related adverse events (TrAE) defined using CTCAE 5.0. Results: The median age was 67 years, 52.8% were female, all patients were past smokers and 97.2% identified as white. The tumor histologies were adenocarcinoma (66.67%), squamous (27.8%), mucinous adenocarcinoma (2.8%) and sarcomatoid (2.8%). Majority were Stage 3B (47.2%) followed by 3C (38.9%) and 3A (13.9%). N2 and N3 disease was noted in 36.1% and 55.6% of patients respectively. PD-L1 by IHC was > 1-49% (47.2%), > 50% (22.2%) and < 1% (19.4%). Patients received ID chemo-IO with pembrolizumab (83.3%), nivolumab (11.1%) and atezolizumab (2.78%). Average number of ID chemo-IO cycles were 3.67 cycles. The ORR to ID chemo-IO was 86.11%. The median PFS was 23.67 mths and the median OS was 32.07 months. About 94% of patients received CRT afterwards and 66.67% received maintenance IO with pembrolizumab (53.17%) or durvalumab (45.83%). Any grade TrAE occured in 58.33% of patients. Pneumonitis was the most common event (38.9%). Grade 3 -4 pneumonitis was noted in 28.5% (4/11) patients. Other toxicities included hepatitis (8.3%), colitis (11.1%) and myasthenia gravis (2.8%) and 22% of these TrAE’s were grade 3 or 4. Conclusions: Our results indicate that ID chemo-IO shows promise as a therapeutic approach for patients with unresectable stage III NSCLC, especially for patients deemed ineligible or high risk for upfront radiation. Further investigation is needed through a randomized clinical trial to systematically explore and validate the safety and efficacy of ID chemo-IO.

The effect of the relative dose intensity of chemoradiotherapy on the effectiveness of therapy of locally advanced unresectable non-small cell lung cancer

The purpose of the study. To estimate the number of patients with the preservation of relative dose intensity (RDI) ≥ 80 % of first-line antitumor therapy in patients with unresectable non-small cell lung cancer (NSCLC), and to compare the effectiveness of therapy in groups with optimal and lower RDI.Patients and methods. The study included 30 patients (25 men and 5 women) with locally advanced unresectable NSCLC. The median age was 57 years. The main criterion for inclusion in the study was morphologically verified NSCLC with stage IIIB-IIIC of the disease. All patients underwent simultaneous chemoradiotherapy. According to the histogenesis of the tumor process, patients with a squamous cell variant prevailed.Results. The data obtained from 22 (73.3 %) patients who retained a relative dose intensity of RDI > 80 % demonstrated that given dose intensity is sufficient to achieve a stable antitumor effect. In 8 (26.7 %) cases, however, the RDI was less than 80 %, which affected the effectiveness of the treatment. The median follow-up for overall survival (OS) was 29.2 months, progression-free survival (PFS) was 15.1 months, and local control was 21.9 months. in all patients included in the analysis. The indicators of OS in the second year had an advantage in the group of patients with RDI < 80 % and amounted to 73.3 % compared with 60.5 % in patients with RDI > 80 %. PFS was higher in the group of patients with high dose intensity, in the first year of follow-up it was 75.6 % compared with the group of patients with RDI < 80 % (62.5 %), in the second year of follow-up, PFS was 27.2 % and 20.8 %, respectively. Local control was 90.2 % in the first year in the group of patients with RDI > 80 % and 62.5 % in the group of patients with RDI < 80 %. The second year of follow-up demonstrated the advantage of the group of patients with RDI >80 % in terms of local control and amounted to 48.1 % versus 34.7 %, respectively.Conclusion. The results obtained show that maintaining relative dose intensity at a high level has a positive effect on survival rates and local control of patients with locally advanced unresectable NSCLC. However, there is a cohort of patients who did not receive the planned amount of treatment, due to the high toxicity of simultaneous chemoradiotherapy. It is necessary to develop new approaches to concomitant therapy aimed at reducing the toxicity of the combined treatment and achieving maximum antitumor effect.

Prognostic Value of the Geriatric Nutritional Risk Index in Previously Untreated Patients with Advanced Non-Small Cell Lung Cancer Treated with a Combination Therapy of Anti-PD-1/-PD-L1 Antibodies and Platinum-Based Chemotherapy: A Multicenter Retrospective Study

Introduction: Combination therapy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies and platinum-based chemotherapy has been widely used as a first-line treatment for patients with unresectable advanced non-small cell lung cancer (NSCLC) in clinical settings; however, prognostic biomarkers associated with survival outcomes have not been sufficiently investigated. Methods: We enrolled 147 previously untreated patients with advanced NSCLC who were treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy at eight institutions in Nagano Prefecture between December 2018 and April 2023. We evaluated the prognostic value of the geriatric nutritional risk index (GNRI), a systemic inflammatory nutritional biomarker calculated from body weight and serum albumin level, for patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy. Results: The cutoff value of the GNRI was set at 92. The high GNRI and low GNRI groups included 88 and 59 patients, respectively. The median follow-up period was 15.9 months. The overall survival (OS) in the high GNRI group was significantly longer than that in the low GNRI group (27.9 vs. 15.6 months, p = 0.015). Multivariate analysis revealed that a high GNRI was an independently favorable prognostic predictor for OS (hazard ratio, 1.73; 95% confidence interval, 1.06–2.86; p = 0.031). Conclusion: The present study demonstrates that the GNRI is a useful prognostic predictor in patients with NSCLC treated with a combination therapy of anti-PD-1/-PD-L1 antibodies and platinum-based chemotherapy in clinical settings.

First exploration of the on-treatment changes in tumor and organ uptake of a radiolabeled anti PD-L1 antibody during chemoradiotherapy in patients with non-small cell lung cancer using whole body PET

BackgroundIn patients with locally advanced unresectable non-small cell lung cancer (NSCLC), durvalumab, an anti-programmed cell death ligand-1 (PD-L1) antibody, has shown improved overall survival when used as consolidation therapy following...

Cost-Effectiveness Analysis of Atezolizumab versus Platinum-Based Chemotherapy as First-Line Treatment for Patients with Unresectable Advanced Non-small Cell Lung Cancer with PD-L1 Expression Status in Japan.

Atezolizumab has demonstrated safety and efficacy in patients with metastatic non-small cell lung cancer (NSCLC) in the IMpower110 trial. The aim of this study was to evaluate thecost-effectiveness of atezolizumab as the first-line treatment for patients with unresectable advanced NSCLC, including programmed cell death ligand-1 (PD-L1)-positive probability testing, from the perspective of healthcare costs in Japan. A cost-effectiveness analysis model for atezolizumab, including PD-L1-positive probability testing, was used toconstruct a partitioned survival model with three health states. To assess the robustness, aprobabilistic sensitivity analysis (PSA) was conducted. The acceptable probability wasdefined asthe probability of willingness-to-pay (WTP) over theincremental cost-effectiveness ratio (ICER). Multiple repetitions at WTP thresholds were calculated by continuously reducing the atezolizumabprice. The ICER per quality-adjusted life year (QALY) for atezolizumab therapy only for patients with high PD-L1 expressioncompared to platinum-based chemotherapy for all patients was 31,975,792 yen per QALY. This is higher than the WTP threshold of 15,000,000yen. If the cost of atezolizumab were reduced to 54% of theoriginal cost (563,917 yen), the strategy of using atezolizumab for patients with high PD-L1 could become more cost-effective. The results indicated that atezolizumab was not cost-effective compared to platinum-based chemotherapy as a first-line treatment for patients with unresectable advanced NSCLC. However, we suggest that the price of atezolizumab shouldbe reduced to 54% of theoriginal cost to meet the WTP threshold of 15,000,000 yen per QALY.

The timing of durvalumab administration affects the risk of pneumonitis in patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis

PurposeThe PACIFIC study has demonstrated that the administration of durvalumab following concurrent chemoradiotherapy can significantly improve both overall survival and progression-free survival rates in patients with locally advanced unresectable non-small cell lung cancer. While the latest NCCN guidelines recommend this combination regimen, they do not specify the optimal timing for administering durvalumab after completing radiotherapy. The PACIFIC study suggested initiating durvalumab within 42 days of completing radiotherapy, but early administration of the drug may increase the incidence of pneumonitis. Therefore, we conducted this study to investigate whether the time interval between completion of radiotherapy and initiation of durvalumab treatment is associated with the risk of pneumonitis (Grade ≥ 3), which is the primary endpoint, as well as progression-free survival, which is the secondary endpoint.MethodsA comprehensive search of clinical trials in PubMed and EMBASE was conducted up to March 2023 to identify clinical trials involving locally advanced unresectable non-small cell lung cancer patients who were treated with durvalumab following chemoradiotherapy. Meta-analysis was performed on single-arm studies to estimate the incidence of pneumonitis (Grade ≥ 3) and progression-free survival in all studies, as well as in studies that administered durvalumab within 42 days after completion of radiotherapy.ResultsThis meta-analysis consisted of nine studies with a total of 2560 patients. The analysis showed that the incidence of pneumonitis (Grade ≥ 3) was 5.36% [95%CI (0.03, 0.08), I2 = 18.41%, p = 0.29], while the 1-year progression-free survival rate was 57.91% [95%CI (0.53, 0.63), I2 = 10.57%, p = 0.35]. Furthermore, when the duration between completion of radiotherapy and initiation of durvalumab treatment was shorter than 42 days, the incidence of pneumonitis (Grade ≥ 3) was 4.12% [95%CI (0.02, 0.06), I2 = 0.00%, p = 0.56], with a 1-year progression-free survival rate of 61.03% [95%CI (0.51, 0.71), I2 = 59.06%, p = 0.09].ConclusionOverall, based on the available evidence, it appears that there is no significant increase in pneumonitis or decrease in progression-free survival (PFS) when the time interval is less than 42 days and a shorter interval between treatment sessions does not necessarily have a detrimental effect on the rate of pneumonitis. We recommend that clinicians carefully evaluate the specific circumstances of each patient to determine the optimal timing for initiating immunotherapy.

Long-term survival outcome of radiation therapy for unresectable, locally advanced non-small cell lung cancer: Single center experience at Hospital 175.

142 Background: Lung cancer represents a significant global health burden, with non-small cell lung cancer (NSCLC) being the most prevalent form of this disease. While surgery remains the cornerstone of treatment for early-stage NSCLC, patients with locally advanced or inoperable NSCLC require alternative therapeutic strategies. Purpose: to assess the long-term survival data and determine the associated factors impacting survival outcomes for patients with locally advanced unresectable non-small cell lung cancer (NSCLC) treated with radiotherapy. Methods: We retrospectively analyzed patients diagnosed with inoperable stage III of NSCLC who received radiation therapy at Hospital 175 from January 2019 to June 2022. The patients had a performance status score (PS) of 0-2 and only one primary lung tumor. We collected patients' background information, including age, gender, pathology, TNM, combination chemotherapy, PET/CT characteristics, and radiotherapy plan parameters. All patients received radiotherapy, at a dose equivalent to 60Gy or more. During radiation therapy, patients were monitored for radiation toxicity. We used the Kaplan-Meier method to estimate overall survival (OS) rate and the Cox regression model to identify the risk factors affecting the treatment outcomes. Results: A total of 240 cases, male: 75%, PS 0, 1, 2 respectively: 24%, 72%, 4%. Histopathological types: squamous cell (9%), glandular cell (83.5%), others (7.5%). Which, subgroups of stages IIIA, IIIB, and IIIC: are 32%, 48%, and 20%. The rate of patients having chemotherapy before radiation was 80.3%, and having PET/CT scans was 43.5%. Patients with radiation alone: 73.4% and concurrent chemoradiotherapy: 26.6%. Median follow-up time: 16.3 months, median OS: 19.5 months. OS rates after 1, 2, and 3 years are 76.2%, 38.8%, and 27.4%, respectively. The most common toxicity was grade 2 esophagitis. Patients who received concurrent chemoradiotherapy had a better prognosis than those who received radiation therapy alone. Regimen of radiation therapy, age, histopathological type, and lymph node metastasis were significant factors affecting overall survival outcomes. Conclusions: Radiotherapy is an essential part of treatment for inoperable NSCLC. The best survival benefit is achieved with concurrent chemoradiotherapy. Besides, age, lymph node metastasis, and histopathological type are also potential factors that can influence patient outcomes.

Salvage surgery for advanced non-small cell lung cancer following previous immunotherapy: a retrospective study

BackgroundThe development of systemic chemotherapy including immune checkpoint inhibitors (ICIs) has provided patients with unresectable advanced non-small cell lung cancer (NSCLC) an opportunity to undergo surgical intervention after initial treatment. However, no consensus regarding the indication for salvage surgery in these patients has been reached.MethodsWe conducted a retrospective study of patients who underwent salvage surgery for advanced NSCLC (cStage IIIA–IVB) after treatment with ICIs from January 2018 to December 2022 at Aizu Medical Center and Fukushima Medical University Hospital. We evaluated the patients’ clinical data, calculated disease-free survival (DFS) and overall survival (OS), and assessed the survival benefit using the Kaplan–Meier method.ResultsThirteen patients underwent salvage surgery after immunotherapy. All patients achieved downstaging after initial chemotherapy. Eleven patients underwent lobectomy, and one patient underwent extirpation of intra-abdominal lymph nodes. The mean surgery time and intraoperative blood loss were 242.2 min and 415.1 g, respectively. The mean drainage period was 4.2 days (range, 2–9 days). Grade ≥ 3 postoperative complications were confirmed in three patients. The 2-year DFS rate was 71.2%, and the 2-year OS rate was 76.2%. A pathological complete response compatible with ypStage 0 was achieved in four (30.8%) patients. Patients with ypStage 0 and I achieved significantly better OS than those with ypStage ≥ II (p = 0.044), and patients without severe complications achieved significantly better DFS and OS than those with severe complications (p = 0.001 and p < 0.001, respectively).ConclusionsSalvage surgery after chemotherapy including ICIs is a feasible and effective treatment option for patients with advanced NSCLC, especially those who acquire downstaging to pathological stage 0 or I. However, severe perioperative complications might affect patient survival. A prospective study is urgently needed to evaluate the efficacy of salvage surgery.

132TiP Boosting immune response with copanlisib in locally advanced unresectable non-small cell lung cancer starting durvalumab consolidation: A phase Ib study

132TiP Boosting immune response with copanlisib in locally advanced unresectable non-small cell lung cancer starting durvalumab consolidation: A phase Ib study

Anatomic lung resection after immune checkpoint inhibitors for initially unresectable advanced-staged non-small cell lung cancer: a retrospective cohort analysis.

Patients with initially unresectable advanced non-small cell lung cancer (NSCLC) might experience prolonged responses under immune checkpoint inhibitors (ICIs). In this setting, Multidisciplinary Tumor Board (MTB) seldomly suggest surgical resection of the primary tumor with the ultimate goal to eradicate macroscopic residual disease. Our objective was to report the perioperative outcomes of patients who underwent anatomic lung resection in these infrequent circumstances. We set a retrospective multicentric single arm study, including all patients with advanced-staged initially unresectable NSCLC (stage IIIB to IVB) who received systemic therapy including ICIs and eventually anatomical resection of the primary tumor in 10 French thoracic surgery units from January 2016 to December 2020. Coprimary endpoints were in-hospital mortality and morbidity. Secondary endpoints were the rate of complete resection of the pulmonary disease, major pathologic response, risk factors associated with post-operative complications, and overall survival. Twenty-one patients (median age 64, female 62%) were included. Eighteen patients (86%) progressed after first line chemotherapy and received second line ICI. The median time between diagnosis and surgery was 22 months [interquartile range (IQR) 18-35 months]. Minimally-invasive approach was used in 10 cases (48%), with half of these requiring conversion to open thoracotomy. Nine patients (43%) presented early post-operative complications, and one patient died from broncho-pleural fistula one month after surgery. Rates of complete resection of the pulmonary disease and major pathologic response were 100% and 43%, respectively. In univariable analysis, diffusing capacity for carbon monoxide (DLCO) was the only factor associated with the occurrence of postoperative complications (P=0.027). After a median follow-up of 16.0 months after surgery (IQR, 12.0-30.0 months), 19 patients (90%) were still alive. Anatomic lung resections appear to be a reasonable option for initially unresectable advanced NSCLC experiencing prolonged response under ICIs. Nonetheless, minimally invasive techniques have a low applicability and post-operative complications remains higher in patients who had lower DLCO values. The late timing of surgery may also contribute to complications.

Pralsetinib (Gavreto)

&#x0D; CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.&#x0D; The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.&#x0D; This review assesses pralsetinib (Gavreto), 400 mg (four 100 mg oral tablets once daily).&#x0D; Indication: For the treatment of adult patients with rearranged during transfection (RET) fusion–positive locally advanced unresectable or metastatic non-small cell lung cancer.&#x0D;

Tepotinib (Tepmetko)

&#x0D; CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.&#x0D; The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.&#x0D; This review assesses tepotinib (Tepmetko), tablets, 225 mg tepotinib (as tepotinib hydrochloride), oral.&#x0D; Indication: For the treatment of adult patients with locally advanced unresectable or metastatic non-small cell lung cancer harbouring MET tyrosine kinase receptor exon 14 skipping alterations.&#x0D;

EP05.01-011 Real World Outcomes of Durvalumab after Chemoradiotherapy in unresectable advanced Non-Small Cell Lung Cancer: The Mayo Clinic Experience

Concurrent chemoradiation followed by durvalumab has become the standard of care in patients with unresectable, locally advanced NSCLC based on the PACIFIC trial. Real life data of this practice are emerging, but few data are available on outcomes of patients with progression of disease after this treatment.

A Phase II Open-Label Multi-center Trial of Isotoxic Hypofractionated Radiotherapy for NSCLC

Background: The standard treatment for advanced unresectable non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. However, many poor Karnofsky score or elderly patients cannot tolerate it due to heir serious side effects. For patients who cannot tolerate concurrent chemoradiotherapy, conventional treatment is sequential chemoradiotherapy or radiotherapy alone. But the median survival time of sequential chemoradiotherapy and radiotherapy alone is 11-16 months. In order to improve curative effect, radiotherapy, as an important treatment method, has been tried, innovated and improved continuously. The goal of this trial is to evaluate feasibility and safety of isotoxic hypofractionated radiotherapy in patients with NSCLC.&#x0D; Methods: This is a phase Ⅱ open-label multi-center two-step non-randomised Trial. In the first stage, 12 patients will be included in the trial with radiotherapy of 3Gy per fraction. If more than 3 patients have serious side effects of radiotherapy, the trial will be terminated. Otherwise, the second phase will continue, and the total number of participants will be 30. All patients eventually will be followed up for 5 years.&#x0D; The primary endpoint is the safety of isotoxic hypofractionated radiotherapy. The secondary outcomes are time to progression (TTP), progression free survival (PFS), overall survival (OS), local control (LC).&#x0D; Discussion: In clinical practice, the local control rate of conventional fractionated radiotherapy for NSCLC is very low. We hope that this trial can verify the safety of isotoxic hypofractionated radiotherapy.&#x0D; Trial Registration: NCT03606291, REGISTERED JULY, 30, 2018.

COMPARATIVE STUDY OF CONCURRENT CHEMORADIATION USING PACLITAXEL IN TWO HISTOPATHOLOGICAL SUBTYPES (SQUAMOUS CELL CARCINOMA/ADENOCARCINOMA) OF UNRESECTABLE NON-SMALL CELL LUNG CANCER

Background. Lung cancer is still a global burden and with rising population and increasing life expectancy the incidence of lung cancer is still on the rise. Objective. To compare the treatment response and toxicity of weekly paclitaxel in locally advanced unresectable non-small cell lung cancer (NSCLC), when administered concurrently with external beam radiation to the chest in two different histopathological types – adenocarcinoma and squamous cell carcinoma. Methods. A prospective randomised control trial was conducted in 60 NSCLC patients who were divided into two arms; adenocarcinoma and squamous cell carcinoma arm. All patients were treated with chemoradiation with concurrent paclitaxel 60 mg/m2. Data were evaluated with SPSS version 21.0 for windows with p-value &lt;0.05. Results. Haematological toxicity was the most common side effects evident from the third week of chemotherapy. At the end of 1 month of treatment, two (6.7%) patients had complete response in Arm A and one (3.3%) patient had complete response in Arm B. One (3.3%) patient had disease progression in Arm A and two patients progressed in Arm B. At 7 months post treatment three (10%) patients had complete response in both Arm A and Arm B. Four (13.3%) patients had disease progression in Arm A and ten (33.4%) patients progressed in Arm B. Conclusions. Paclitaxel can be used as an alternative chemotherapeutic agent to the standard cisplatin. However, further studies with larger sample size are required to confirm the findings.

Emerging biomarkers for neoadjuvant immune checkpoint inhibitors in operable non-small cell lung cancer.

The advent of immune checkpoint inhibitors (ICIs) has dramatically changed the treatment of patients with locally advanced unresectable and metastatic non-small cell lung cancer (NSCLC). Now, ICIs are undergoing evaluation as neoadjuvant therapy in patients with early-stage, resectable NSCLC using candidate surrogate endpoints of clinical efficacy, i.e., major pathologic response (MPR, ≤10% viable tumor cells in resected tumors). The initial results from early, small-scale trials are encouraging; however, they also reveal that a substantial number of patients with operable disease may not benefit from neoadjuvant ICIs. Consequently, much investigative effort is currently directed toward identifying mechanisms of resistance to ICI therapy in resectable NSCLC. There is also an urgent need for biomarkers that could be used to guide the clinical decision-making process and maximize the clinical benefit of ICIs in patients with early-stage, resectable NSCLC. Here, we summarize the initial results from the trials of neoadjuvant ICIs in patients with early-stage and locally advanced operable NSCLC and review the findings of studies investigating emerging biomarkers associated with those trials.

Bronchoplastic Procedure Versus Pneumonectomy After High-dose Radiation for Non-small Cell Lung Cancer

Studies have revealed that salvage surgery after definitive chemoradiotherapy (CRT) for unresectable advanced non-small cell lung cancer improves survival with acceptable surgical adverse events. Few reports exist regarding pneumonectomy or the bronchoplastic procedure in this setting. Between 2008 and 2018, 27 patients (21 men; median age, 61 years) underwent salvage surgery after definitive CRT for non-small cell lung cancer. We investigated postoperative short- and long-term outcomes of salvage surgery and aimed to elucidate the feasibility of pneumonectomy or the bronchoplastic procedure. The median radiation dose was 60 Gy. The median period from the last day for irradiation to the operative day was 8.5 months. Pneumonectomy was performed in 9 patients, including 2 carinal resections; lobectomy was performed in 18 patients, including 5 bronchoplasties. Bronchial wrapping was performed in 9 cases (33%), R0 resection was achieved in 24 (89%), and postoperative complications were detected in 16 (59%). Although bronchopleural fistulas were found in only 2 patients who underwent pneumonectomy, arrhythmia was observed more frequently in patients who underwent the bronchoplastic procedure (P= .05). Regarding major complications, no relationship with any factors were found. The 90-day mortality was 0%. The 5-year overall and recurrence-free survival were 63% and 27%, respectively. R0 resection was a good prognostic factor for recurrence-free survival (P= .001). Perioperative short- and long-term outcomes of salvage surgery after definitive CRT for non-small cell lung cancer were acceptable. Complete resection offered a better recurrence-free survival. The bronchoplastic procedure or pneumonectomy should be considered as an option even after administration of high-dose CRT.

Erlotinib Versus Etoposide/Cisplatin With Radiation Therapy in Unresectable Stage III Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Multicenter, Randomized, Open-Label, Phase 2 Trial

This study aimed to compare erlotinib (E) and etoposide/cisplatin (EP) with concurrent radiation therapy (RT) for patients with stage IIIA/B unresectable advanced non-small cell lung cancer with activating epidermal growth factor receptor mutation (EGFRm+). This was a multicenter, randomized, open-label, phase 2 trial conducted across 19 institutions in China (December 2012 to January 2016). Enrolled patients were randomized (1:1) to E + RT (oral erlotinib 150 mg/d for 2 years or until disease progression or intolerable toxicity and RT 200 cGy/d, 5 d/wk for 6 weeks from the first day of erlotinib) or EP + RT (etoposide 50 mg/m2 intravenously on days 1-5 and 29-33; cisplatin 50 mg/m2 intravenously on days 1, 8, 29 and 36; and RT as for E + RT). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate and safety. Two hundred fifty-two patients were screened, and 20 patients with EGFRm+ in each group received the allocated E + RT or EP + RT treatment. Patient characteristics were well balanced between groups. Compared with EP + RT, median PFS with E + RT was significantly longer (24.5 vs 9.0 months [hazard ratio, 0.104; 95% confidence interval, 0.028-0.389; P < .001]). Objective response rate in the E + RT and EP + RT groups was 70% and 61.9%, respectively (P = .744). The incidence of adverse events (any grade) was similar between E + RT and EP + RT groups (88.9% and 84.2%). The primary endpoint of PFS was met, and the data showed that E + RT might provide PFS improvement compared with EP + RT, with similar tolerability. However, definitive statements regarding the efficacy of concurrent E + RT in patients with unresectable stage III non-small cell lung cancer with activating EGFRm+ cannot be made, and slow patient accrual will likely make it infeasible to conduct a phase 3 study.

Durvalumab after definitive chemoradiotherapy in locally advanced unresectable non-small cell lung cancer (NSCLC): Real-world data on survival and safety from the German expanded-access program (EAP)

BackgroundFollowing the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.2017 to 15.10.2018 allowing analysis of its efficacy and safety. MethodsData from 56 centres were analysed for adverse events (AE), progression-free survival (PFS), overall survival (OS). Results126 patients actually received at least 1 cycle durvalumab. Compared to the PACIFIC trial, the EAP population had more advanced stage and included “oligometastatic” stage IV patients and patients with autoimmune disease. PFS (20.1 months) and OS (not reached) were similar in the EAP and the PACIFIC trial. 42.9 % completed 12 months of durvalumab without deaths during FU. Stage IV patients (n = 7) had encouraging OS (not reached at 27 months). Autoimmune disease did not affect survival. PFS and OS were similar in PD-L1-negative patients (n = 32) and PD-L1-positive patients (n = 79). ConclusionsSurvival in the EAP was comparable to the PACIFIC trial. Selected stage IV patients and patients with autoimmune disease may benefit from durvalumab consolidation and should be included in future immuno-oncological trials. PD-L1 did not predict survival challenging the exclusion of PD-L1-negative patients from durvalumab consolidation. In summary, durvalumab consolidation is safe and effective in a European real-world setting.