Durvalumab Consolidation Therapy Research Articles

Patterns and Incidence of Pneumonitis and Initial Treatment Outcomes with Durvalumab Consolidation Therapy after Radical Chemoradiotherapy for Stage III Non-Small Cell Lung Cancer.

Durvalumab consolidation after chemoradiotherapy for stage III non-small cell lung cancer (NSCLC) has become the standard of care. Single-center results were examined for treatment outcomes and patterns of pneumonitis in clinical practice. Patients with stage III NSCLC who underwent chemoradiotherapy at our institution (n = 150) were included. The patients were treated with chemoradiotherapy and durvalumab consolidation (Group D, n = 69) or chemoradiotherapy alone (Group N, n = 81). The overall survival (OS), progression-free survival (PFS), and the incidence of and risk factors for 12-month pneumonitis grade ≥ 2 (G2) were investigated. Two-year OS rates were 71.6% in Group D and 52.7% in Group N (p = 0.052). Two-year PFS rates were 43.0% in Group D and 26.5% in Group N (p = 0.010), although a propensity score matched analysis showed no significant difference. The incidence of 12-month pneumonitis ≥ G2 tended to be higher in Group D than in Group N (41.9% vs. 26.3%, p = 0.080). However, there was no difference in pneumonitis ≥ G3 rates (10.5% vs. 12.6%, p = 0.657). A multivariate analysis showed that the lung volume spared from 5 Gy (VS5) < 1800 cm3 was a risk factor for pneumonitis ≥ G2 in Group D. Durvalumab consolidation showed the potential to prolong PFS without increasing the severity of pneumonitis.

Durvalumab Outcomes in Stage III Non-small Cell Lung Cancer: A Single-institution Study.

The PACIFIC trial demonstrated improved survival in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with durvalumab following definitive concurrent chemoradiotherapy (CRT). This study sought to explore real-world outcomes with durvalumab consolidation therapy at our institution. We retrospectively identified patients diagnosed with stage III NSCLC at our institution from January 2012 to January 2022. We created two cohorts: one who received durvalumab following definitive CRT and a historical one who did not. Primary outcomes of interest included median progression-free survival (PFS) and overall survival (OS). Additionally, we performed subgroup analysis on the durvalumab cohort to explore the associations between survival and time to durvalumab initiation, PD-L1 expression, and neutrophil-to-lymphocyte ratio (NLR). We identified 79 patients with locally advanced NSCLC who were not surgical candidates. Patients treated with durvalumab (n=44) had significantly improved survival compared to the historical cohort (n=35) including a median PFS of 17.4 months versus 8.0 months (p=0.0019) and a median OS of 37.0 months versus 17.0 months (log-rank p-value=0.07, Wilcoxon p-value=0.02). Within the durvalumab group, outcomes did not significantly differ between those who initiated therapy before or after 42 days of finishing CRT, between various PD-L1 expression levels, or between high or low NLR. Patients who received durvalumab as consolidation therapy following definitive CRT demonstrated significantly improved survival compared to a historical cohort who did not receive durvalumab. Furthermore, durvalumab appears to benefit patients regardless of time to initiation, PD-L1 expression, or NLR.

The role of chemoradiotherapy and immunotherapy in stage III NSCLC.

Locally advanced non-small lung cancer encompasses a diverse range of tumors. In the last few years, the treatment of stage III unresectable non-small lung cancer has evolved significantly. The PACIFIC trial opened a new therapeutic era in the treatment of locally advanced NSCLC, establishing durvalumab consolidation therapy as the new standard of care worldwide. A careful evaluation of this type of lung cancer and a discussion of the management of these patients within a multidisciplinary team represents a crucial step in defining the best treatment strategy for each patient. For unresectable stage III NSCLC, definitive concurrent chemoradiotherapy (CCRT) was historically recommended as a treatment with a 5-year survival rate ranging from 20% to 30%. The PACIFIC study conducted in 2017 compared the use of chemoradiotherapy and maintenance therapy with the anti-PD-L1 monoclonal antibody durvalumab to a placebo in patients with locally advanced NSCLC who had not experienced disease progression. The study was prospective, randomized, and phase III. The administration of this medication in patients with locally advanced non-small cell lung cancer (NSCLC) has demonstrated a notable improvement in overall survival. Multiple clinical trials are currently exploring various immune checkpoint inhibition regimens to enhance the treatment efficacy in patients with stage III cancer. Our goal is to offer an up-to-date summary of the planned clinical trials for treatment options, focusing on the significant obstacles and prospects in the post-PACIFIC era.

EP08.02-13 Association of the Benefit of Durvalumab Consolidation Therapy and Driver Mutation Status for Locally Advanced Non-small Lung Cancer

EP08.02-13 Association of the Benefit of Durvalumab Consolidation Therapy and Driver Mutation Status for Locally Advanced Non-small Lung Cancer

Pneumonitis During Durvalumab Consolidation Therapy Affects Survival in Stage III NSCLC

IntroductionDurvalumab consolidation therapy is the standard of care after concurrent chemoradiotherapy (CRT) for stage III NSCLC. Immune-related pneumonitis during durvalumab treatment is potentially fatal; however, information is lacking regarding the impact of pneumonitis on patient survival. This study investigates the effect of pulmonary and nonpulmonary immune-related adverse events (irAEs) on the efficacy of durvalumab treatment in patients with stage III NSCLC. MethodsWe retrospectively assessed 158 patients who received durvalumab after CRT at nine Japanese institutions between July 2018 and March 2020. Survival outcomes were compared between patients who developed pneumonitis with those who developed irAEs other than pneumonitis. Patients who survived for less than 3 months were excluded to reduce immortal time bias. ResultsAmong 158 evaluated patients, 76 (48%) experienced grade less than or equal to one irAEs, whereas 82 (52%) experienced grade greater than or equal to two irAEs. Among the patients with grade greater than or equal to two irAEs, those with grade greater than or equal to two pneumonitis (n = 55) were compared with those with grade greater than or equal to two irAEs other than pneumonitis (n = 27). Patients with grade greater than or equal to two pneumonitis exhibited a significantly worse overall survival than those with grade greater than or equal to two irAEs that excluded pneumonitis. Multivariate analysis revealed that grade greater than or equal to two pneumonitis (hazard ratio = 3.71; 95% confidence interval, 1.85–7.45; p < 0.001) and squamous histology (hazard ratio = 2.64; 95% confidence interval, 1.29–5.42; p = 0.008) were independently associated with worse overall survival. ConclusionsAfter minimizing immortal time bias, pneumonitis grade two or greater and squamous histology were poor prognostic factors in patients who received consolidation durvalumab after CRT.

Exploratory analysis to predict pneumonitis during durvalumab consolidation therapy for patients with locally advanced non-small cell lung cancer from proteomic profiling of circulating extracellular vesicles.

Risk factors for predicting pneumonitis during durvalumab consolidation after chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (LA-NSCLC) are still lacking. Extracellular vesicles (EVs) play a crucial role in intercellular communication and are potential diagnostic tools for various diseases. We retrospectively collected predurvalumab treatment serum samples from patients treated with durvalumab for LA-NSCLC, isolated EVs using anti-CD9 and anti-CD63 antibodies, and performed proteomic analyses. We examined EV proteins that could predict the development of symptomatic pneumonitis (SP) during durvalumab treatment. Potential EV-protein biomarkers were validated in an independent cohort. In the discovery cohort, 73 patients were included, 49 with asymptomatic pneumonitis (AP) and 24 with SP. Of the 5797 proteins detected in circulating EVs, 33 were significantly elevated (fold change [FC] > 1.5, p < 0.05) in the SP group, indicating enrichment of the nuclear factor kappa B (NF-κB) pathway. Patients with high levels of EV-RELA, an NF-κB subunit, had a higher incidence of SP than those with low levels of EV-RELA (53.8% vs. 13.4%, p = 0.0017). In the receiver operating characteristic analysis, EV-RELA demonstrated a higher area under the curve (AUC) than lung V20 (0.76 vs. 0.62) and was identified as an independent risk factor in the multivariate logistic regression analysis (p = 0.008, odds ratio 7.72). Moreover, high EV-RELA was also a predictor of SP in the validation cohort comprising 43 patients (AUC of 0.80). Circulating EV-RELA may be a predictive marker for symptomatic pneumonitis in patients with LA-NSCLC treated with durvalumab.

Identification of predictive factors for early relapse in patients with unresectable stage III non-small cell lung cancer receiving consolidation durvalumab after concurrent chemoradiation therapy.

Patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) receiving definitive concurrent chemoradiation therapy (CCRT) benefit from durvalumab consolidation therapy. However, predictive factors for early relapse during durvalumab maintenance have not yet been identified. The present study included the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from January 2018 to December 2021. A total of 51 NSCLC patients treated with durvalumab consolidation therapy after definitive CCRT were included in the analysis. Early relapse was defined as patients experiencing relapse within 6 months of starting initial durvalumab therapy. Among the 51 patients, 15 (29.4%) relapsed during the study period. Median time from initial therapy of durvalumab to progression was 451.00 ± 220.87 days (95% confidence interval [CI]: 18.10-883.90) in overall patients. In multivariate analysis, younger age (adjusted odds ratio [aOR], 0.792; 95% CI: 0.642-0.977; p = 0.030), higher pack-years (aOR, 1.315; 95% CI: 1.058-1.635; p = 0.014), non-COPD (aOR, 0.004; 95% CI: 0.000-0.828; p = 0.004) and anemia (aOR, 234.30; 95% CI: 1.212-45280.24; p = 0.042), were independent predictive factors for early relapse during durvalumab consolidation therapy. Younger age, higher number of pack-years, non-COPD, and anemia were independent predictive factors for early relapse during durvalumab consolidation therapy in patients with unresectable stage III NSCLC after definitive CCRT. Careful patient selection and clinical attention are needed for high-risk individuals.

Durvalumab real-world treatment patterns and outcomes in patients with stage III non-small-cell lung cancer treated in a US community setting.

Background: For eligible patients with unresectable stage III non-small-cell lung cancer, durvalumab consolidation therapy following chemoradiotherapy is the standard of care. Methods: This was a retrospective study of durvalumab-treated patients diagnosed between 1 August 2017 and 29 February 2020. Electronic health record data were assessed descriptively, with Kaplan-Meier methods used for duration of treatment and overall survival (OS). Results: Among 528 patients (median age 70years, 51.5% male), the median duration of treatment was 7.1months (95% CI: 6.0-9.0). Estimated 1- and 2-year OS rates were 83.5 and 64.0%, respectively, with median OS not reached. Conclusion: This study confirmed an OS benefit with durvalumab after chemoradiotherapy in a real-world setting, consistent with the results from the PACIFIC phase III clinical trial.

Concurrent durvalumab plus chemoradiation therapy followed by durvalumab in Chinese patients with unresectable stage III non-small cell lung cancer: CRUISER study.

e20576 Background: Concurrent chemoradiation therapy (CRT) followed by durvalumab consolidation therapy has demonstrated significant survival benefit for unresectable stage III non-small cell lung cancer (NSCLC) in PACIFIC trial. However, there are still 20%-30% patients who have disease progression (PD) or intolerable toxicity. This prospective study aimed to evaluate safety and clinical activity of concurrent durvalumab plus CRT followed by durvalumab in unresectable stage III NSCLC (NCT04982549). Methods: This is a single-arm, open-label, multicenter phase II clinical trial and planned to enroll 35 patients with unresectable stage III NSCLC of any PD-L1 expression level and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. All of patients will receive concurrent durvalumab 1500mg every 4 weeks plus SoC CRT followed by durvalumab monotherapy 1500mg every 4 weeks until PD or unacceptable toxicity. One cycle of induction durvalumab plus chemotherapy is allowed before radiotherapy upon investigator discretion. The primary endpoint is the incidence of grade ≥3 immune-mediated adverse event (AE). Here we report the preliminary clinical activity and safety of a preplanned interim analysis of this study. Results: By September 2022, 28 patients finished concurrent durvalumab plus CRT treatment and were included for analysis. 21 (75%) of 28 patients had radiographic tumor evaluation and entered the consolidation treatment stage, 7 (25%) patients discontinued treatment without radiographic tumor evaluation because of intolerable AE (5 patients) or withdrawing from the study (2 patients). 20 (71.4%) of 28 patients received one cycle induction therapy of durvalumab plus chemotherapy. The median age of these 28 patients was 64 years old, 26 (92.9%) of 28 patients with ECOG performance status of 1, and 14 (50%) of 28 patients were squamous carcinoma. Disease stage was IIIA (42.9%, 12/28), IIIB (39.3%, 11/28) and IIIC (17.9%, 5/28), with most of them (89.3%, 25/28) had N2/N3 lymphatic metastasis. 19 (90.5%) of 21 patients achieved objective response. Median interval from enrollment to the first radiological evaluation was 112 days. Grade ≥3 treatment-related adverse event (TRAEs) occurred in 13(46.4%) of 28 patients, including six (21.4%) possibly related to durvalumab. Conclusions: The interim results from CRUISER study showed promising clinical activity and manageable toxicity of durvalumab plus concurrent CRT followed by durvalumab for unresectable stage III NSCLC. The survival outcome and biomarker exploration will be analyzed upon data maturity. Phase 3 PACIFIC-2 study investigating clinical outcome of concurrent durvalumab plus CRT in unresectable NSCLC is ongoing. Clinical trial information: NCT04982549 .

Phase 3 study of durvalumab combined with oleclumab or monalizumab in patients with unresectable stage III NSCLC (PACIFIC-9).

TPS8610 Background: Based on the findings of the phase 3 PACIFIC trial, durvalumab as consolidation therapy is the standard of care for patients with unresectable Stage III NSCLC and no disease progression following chemoradiotherapy (CRT; the PACIFIC regimen). However, further improvements in outcomes are needed for this population and, to build upon the backbone of PD-L1 inhibition with durvalumab, immunotherapy combinations including anti-TIGIT, anti-CD73, and anti-NKG2a monoclonal antibodies (mAbs) are now being explored. Two potential candidates, oleclumab and monalizumab, have demonstrated encouraging clinical activity in a randomized, phase 2 trial when combined with durvalumab in this setting. Oleclumab (MEDI9447) is a human IgG1λ mAb that inhibits the function of CD73, to reduce extracellular adenosine production and thus promote antitumor immunity. Monalizumab (IPH2201) is a first-in-class, humanized, IgG4 mAb that prevents NKG2A from binding to HLA-E, which reduces inhibition of natural killer and CD8+ T cells. The combination of each of these molecules with durvalumab consolidation therapy was evaluated in the phase 2 COAST study (NCT03822351). In COAST (n = 189), patients receiving combination therapy reported numerically higher objective response rates (durvalumab plus oleclumab: 30.0%; durvalumab plus monalizumab: 35.5%; durvalumab monotherapy: 17.9%) and prolonged progression-free survival versus durvalumab alone, with no new/significant safety signals (Herbst, et al. 2022). Thus, the combination of oleclumab or monalizumab with consolidative durvalumab warrants further evaluation in a phase 3 trial. Methods: PACIFIC-9 (NCT05221840) is a phase 3, double-blind, placebo-controlled, randomized, international trial. Eligible patients (age ≥18 years) must have EGFR/ALK wild-type unresectable Stage III NSCLC, a WHO performance status of 0/1, documented PD-L1 status, and must not have progressed following ≥2 cycles of definitive, platinum-based concurrent CRT. Approximately 999 patients will be randomized (1:1:1) to receive up to 12 months of treatment (in 28-day cycles) with durvalumab plus either oleclumab (Arm A); monalizumab (Arm B); or placebo (Arm C). The primary endpoint is progression-free survival (RECIST v1.1) by blinded independent central review (BICR). Overall survival is a key secondary endpoint. Other secondary endpoints include objective response rate and duration of response (RECIST v1.1; BICR), patient-reported outcomes, PD-L1 expression on tumor cells relative to efficacy outcomes, and safety/tolerability (CTCAE v5.0). Trial enrollment is ongoing. Previously presented at the World Conference on Lung Cancer (WCLC) 2022, FPN (Final Publication Number): P1.10-01, Fabrice Barlesi et al. Clinical trial information: NCT05221840 .

Durvalumab outcomes for patients with PD-L1 positive and negative stage III unresectable non-small cell lung cancer treated at veterans health administration facilities.

e18793 Background: Clinical trials and real-world studies have documented the benefit of durvalumab consolidation therapy in patients with stage III unresectable non-small cell lung cancer (UR-NSCLC) following chemoradiotherapy (CRT). Methods: Patients with stage III UR-NSCLC on durvalumab following CRT, at any Veterans Health Administration (VHA) facility from 1/1/17 to 6/30/20, were included. Patients were followed from their durvalumab initiation date through the earliest of their last VHA visit, loss to follow up, death, or end of study. Electronic health record and chart review data were retrospectively collected to determine baseline characteristics, number of durvalumab doses, length of follow-up, and overall survival (OS). Chi-square and Wilcoxon rank sum tests were used to compare baseline characteristics for patients with PD-L1 negative (&lt;1%) and positive (1% or greater) tumors. Kaplan-Meier curves were constructed for OS. Cox proportional hazards regression, with controls for divergent baseline characteristics, were used to compare OS between the two groups. Results: Of 935 available patients, 340 had PD-L1 results: 221 had PD-L1 positive (65%) and 119 had PD-L1 negative (35%) tumors. The two groups of patients were largely similar with respect to baseline characteristics, including age, sex at birth, White race, smoking status, marital status, Charlson Comorbidity Index, ECOG status, histology, stage, EGFR, and RAS mutations (Table). Patients with PD-L1 positive and negative tumors had a similar median (interquartile range [IQR]) number of durvalumab doses (15 [6-24] vs 12 [5-23], p=0.38) and length of follow-up (31.5 [12.1-43.5] vs 28.7 [12.2-40.6] months, p=0.43). Kaplan-Meier survival curves were similar for patients with PD-L1 positive and negative tumors: estimated 12-month OS rates (95% CI) of 84% (78%-88%) vs 89% (81%-93%) and 24-month OS rates of 72% (65%-78%) vs 76% (67%-84%); median OS was not reached in patients with PD-L1 positive tumors and was 47.0 months for the PD-L1 negative group. Cox Proportional Hazards regression analysis also demonstrated similar OS for both groups (p=0.64). Conclusions: In this real-world study of a subpopulation of VHA patients with stage III UR-NSCLC and known PD-L1 levels, survival benefits with durvalumab were consistent with those reported in the PACIFIC trial, despite having worse baseline prognostic factors. Patients with PD-L1 positive and negative tumors experienced similar overall survival, including 12- and 24-month OS rates.[Table: see text]

Clinical features and risk factors for interstitial lung disease spreading in low-dose irradiated areas after definitive radiotherapy with or without durvalumab consolidation therapy for patients with non-small cell lung cancer

BackgroundThe current standard of care for patients with unresectable locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) combined with durvalumab consolidation therapy. However, radiotherapy (RT) always carries the risk of radiation pneumonitis (RP), which can preclude durvalumab continuation. In particular, the spread of interstitial lung disease (ILD) in low-dose areas or extending beyond the RT field often makes it difficult to determine the safety of continuation or rechallenging of durvalumab. Thus, we retrospectively analyzed ILD/RP after definitive RT with and without durvalumab, with assessment of radiologic features and dose distribution in RT.MethodsWe retrospectively evaluated the clinical records, CT imaging, and radiotherapy planning data of 74 patients with NSCLC who underwent definitive RT at our institution between July 2016 and July 2020. We assessed the risk factors for recurrence within one year and occurrence of ILD/RP.ResultsKaplan-Meier method showed that ≥ 7 cycles of durvalumab significantly improved 1-year progression free survival (PFS) (p < 0.001). Nineteen patients (26%) were diagnosed with ≥ Grade 2 and 7 (9.5%) with ≥ Grade 3 ILD/RP after completing RT. There was no significant correlation between durvalumab administration and ≥ Grade 2 ILD/RP. Twelve patients (16%) developed ILD/RP that spread outside the high-dose (> 40 Gy) area, of whom 8 (67%) had ≥ Grade 2 and 3 (25%) had Grade 3 symptoms. In unadjusted and multivariate Cox proportional-hazards models adjusted for V20 (proportion of the lung volume receiving ≥ 20 Gy), high HbA1c level was significantly correlated with ILD/RP pattern spreading outside the high-dose area (hazard ratio, 1.842; 95% confidence interval, 1.35–2.51).ConclusionsDurvalumab improved 1-year PFS without increasing the risk of ILD/RP. Diabetic factors were associated with ILD/RP distribution pattern spreading in the lower dose area or outside RT fields, with a high rate of symptoms. Further study of the clinical background of patients including diabetes is needed to safely increase the number of durvalumab doses after CRT.

Abstract 6757: Identification of predictive factors for early relapse in patients with unresectable stage III NSCLC receiving consolidation durvalumab after concurrent chemoradiation

Abstract Background: Patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) receiving definitive concurrent chemoradiation (CCRT) benefit from durvalumab consolidation therapy. However, predictive factors for early relapse during durvalumab maintenance were not identified. Patients and Methods: The present study used the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from 2018 to 2021. In all, 51 NSCLC patients that were treated with durvalumab consolidation therapy after definitive CCRT. Early relapse was considered if it occurred within 6 months of starting initial durvalumab therapy. Results: During study period, 15 (29.4%) relapsed among 51 included patients. Median time from initial therapy of durvalumab to progression was 107.73 ± 47.69 days in early relapse group. In mutivariate analysis, younger age (HR 0.713, 95% CI 0.572-0.888, P=0.003), higher pack years (HR 1.311, 95% CI 1.109-1.549, P=0.001), non-COPD (HR 0.030, 95% CI 0.001-0.677, P=0.027), anemia (HR 23.30, 95% CI 2.030-267.48, P=0.011) and stage IIIC (vs. stage IIIA) (HR 17.890, 95% CI 1.997-160.243, P=0.010) were independent predictive factors for early relapse during durvalumab consolidation therapy. Conclusion: Younger age, higher pack years, non-COPD, anemia and stage IIIC were independent predictive factors for early relapse during durvalumab consolidation therapy in patients with unresectable stage III NSCLC after definitive CCRT. Careful patient selection and clinical attention are needed for high-risk individuals. Citation Format: Chang Dong Yeo, Hye Seon Kang, In Kyoung Kim, Sang Haak Lee, Jin Woo Kim. Identification of predictive factors for early relapse in patients with unresectable stage III NSCLC receiving consolidation durvalumab after concurrent chemoradiation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6757.

Follow-Up Imaging Guidelines for Patients with Stage III Unresectable NSCLC: Recommendations Based on the PACIFIC Trial

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3-5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1-5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.

Impact of Lymphopenia Recovery After Chemoradiotherapy on Durvalumab Consolidation Therapy in Stage III NSCLC

IntroductionDurvalumab maintenance therapy after definitive concurrent chemoradiotherapy (CRT) is the standard treatment modality for stage III NSCLC. Although severe treatment-related lymphopenia (TRL) during CRT may impair the efficacy of subsequent durvalumab therapy, data on the effect of TRL recovery on consolidation durvalumab therapy are lacking. MethodsThis retrospective study evaluated patients with unresectable stage III NSCLC treated with durvalumab after concurrent CRT. The patients were enrolled across nine institutes throughout Japan between August 2018 and March 2020. The effect of TRL recovery on survival was evaluated. The patients were divided into two groups on the basis of their lymphocyte recovery status: the recovery group involved patients who did not experience severe TRL or experienced TRL but exhibited lymphocyte count recovery at durvalumab initiation, and the nonrecovery group involved patients who experienced severe TRL and did not exhibit lymphocyte count recovery on durvalumab initiation. ResultsAmong the 151 patients evaluated, 41 (27%) and 110 (73%) patients were classified into the recovery and the nonrecovery groups, respectively. The nonrecovery group had significantly worse progression-free survival than the recovery group (21.9 mo versus not reached, p = 0.018). Recovery from TRL (p = 0.027) and high pre-CRT lymphocyte count (p = 0.028) independently influenced progression-free survival. ConclusionsBaseline lymphocyte count and recovery from TRL at the start of durvalumab therapy were predictive factors for survival outcomes in patients with NSCLC treated with durvalumab consolidation after concurrent CRT.

OP28 Cost-effectiveness analyses of durvalumab consolidation therapy compared to no consolidation therapy after definitive chemoradiotherapy in stage III NSCLC

OP28 Cost-effectiveness analyses of durvalumab consolidation therapy compared to no consolidation therapy after definitive chemoradiotherapy in stage III NSCLC

The safety and efficacy of durvalumab consolidation therapy in the management of patients with stage III non-small-cell lung cancer and preexisting interstitial lung disease

Some lung cancer patients have preexisting interstitial lung disease (ILD), which is considered a risk factor for lung cancer treatment. This study investigated the safety and efficacy of durvalumab consolidation therapy for patients with stage III non-small-cell lung cancer (NSCLC) and preexisting ILD. Fifty consecutive patients who were judged to be tolerable to concurrent chemoradiotherapy (CCRT) for stage III NSCLC were enrolled. Differences in the incidence rate of radiation pneumonitis (RP) and progression-free survival (PFS) were assessed in patients with or without ILD of which CT showed non-usual interstitial pneumonia pattern between the durvalumab consolidation group and chemotherapy (combination of carboplatin and paclitaxel [CP]) consolidation group. The incidence of RP was higher in patients with preexisting ILD (40% and 20% in the durvalumab and CP groups, respectively) than in those without ILD (26% and 8% in the durvalumab and CP groups, respectively). Univariate analysis showed that durvalumab therapy tended to increase the incidence of RP; however, preexisting ILD did not significantly increase the incidence of RP. The condition of all patients who developed RP improved with the administration of oral prednisolone. Among patients without ILD, the median PFS was 17 and 16 months in the durvalumab and CP groups, respectively. Among patients with preexisting ILD, median PFS was not achieved in the durvalumab group and was 8 months in the CP group. Although durvalumab consolidation therapy tended to increase the incidence of RP, it might be tolerable in stage III NSCLC patients with preexisting ILD.

Neoadjuvant Immunotherapy Combined with Chemotherapy for Local Advanced Non-Small-Cell Lung Cancer in a Patient with a History of Breast Cancer: A Case Report

Durvalumab consolidation therapy is the standard treatment after concurrent chemoradiotherapy for patients with surgically unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Neoadjuvant therapy followed by surgery could reduce locoregional and distant recurrence and improve the survival rate for surgically resectable NSCLC. However, the value of neoadjuvant therapy in locally advanced potentially resectable NSCLC remains controversial. Herein, we report a locally advanced potentially resectable NSCLC case with a history of breast cancer who achieved a pathologic complete response (pCR) after preoperative treatment with pembrolizumab and chemotherapy. A 50-year-old woman developed squamous cell carcinoma (SCC) (left lower lobe of the lung, stage IIIA-N2) after two years of chemotherapy and anti-HER2 therapy following a diagnosis of HER2-overexpressing breast cancer. Surgical resection was attempted despite an MDT classification as unamenable to curative surgical resection. After two cycles of neoadjuvant chemotherapy combined with anti-PD1 immunotherapy, the tumor significantly shrank, then the patient underwent a left lower lobectomy. Complete resection with negative margins (R0 resection) was achieved in the patient. The patient experienced grade 1–2 adverse effects and no grade 3 or worse adverse effects occurred. Cardiotoxicity did not occur in the patient despite prior anti-HER2 treatment for breast cancer. Our case study contributes to the existing evidence on the feasibility, efficacy, and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC. Furthermore, future studies are needed to determine which patients can benefit from immunoadjuvant therapy and the duration and course of preoperative and postoperative immunotherapy.

MO11-1 Efficacy of durvalumab after chemoradiotherapy with daily low-dose carboplatin for unresectable locally advanced NSCLC

On the basis of the PACIFIC trial, the standard of care for unresectable stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by 1 year of durvalumab consolidation therapy. Although CRT with platinum doublet is standard, low-dose carboplatin (CBDCA) is widely used in Japan for patients who are not eligible for platinum-based doublet chemotherapy. However, because only five patients received low-dose CBDCA in the PACIFIC study, the efficacy of durvalumab after CRT with low-dose CBDCA remains unclear.

Cost-effectiveness analyses of durvalumab consolidation therapy versus no consolidation therapy after chemoradiotherapy in stage-III NSCLC

BackgroundNon-small cell lung cancer (NSCLC) is the most common form of lung cancer. Recently, Durvalumab was approved as a potential immunotherapy for the management of unresectable stage III NSCLC. Economic studies from different parts of the world presented varying findings. Therefore, the objective of this study was to assess the cost-effectiveness of durvalumab consolidation therapy versus no consolidation therapy in patients with unresectable stage III NSCLC. MethodsPubMed, Embase, and Cochrane databases were searched till March 2022 to identify all the studies assessing the economic evaluation of durvalumab in patients with unresectable stage III NSCLC who had not progressed after chemoradiotherapy. Eligible studies were screened by two reviewers independently and the quality of included studies was evaluated using the updated version of Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) checklists. All costs were converted to 2022 US dollars ($) by adjusting for the gross domestic product (GDP) deflator index and purchasing power parities for GDP. ResultsA total of seven studies were found to be eligible for inclusion. The majority of studies were conducted in the US (n = 3), while one study each was conducted in China, Italy, Switzerland, and the UK. The healthcare payers’ perspective was most commonly observed among the included studies and the time horizon varied from 5 years to a lifetime. Three studies received funding from Industry. Four included studies used the Markov model, while two employed the semi-Markov model and, one study used decision-analytic model. The ICER of durvalumab consolidation therapy in the US was found to be in the range of $59,850 to $145,543 per Quality-Adjusted Life Years (QALY). Likewise, the ICER of durvalumab in European countries ranged from $62,021 to $76,068 per QALY. The ICER was below the implemented country-specific willingness-to-pay thresholds in all the included studies. ConclusionDurvalumab consolidation therapy was found to be cost-effective compared to no consolidation therapy after chemoradiotherapy in stage-III NSCLC patients.