Ineligibility for the PACIFIC trial in unresectable stage III non-small cell lung cancer patients

Hosoya, Kazumi; Fujimoto, Daichi; Kawachi, Hayato; Sato, Yuki; Kogo, Mariko; Nagata, Kazuma; Nakagawa, Atsushi; Tachikawa, Ryo; Hiraoka, Shinya; Kitajima, Masaki; Tomii, Keisuke

doi:10.1007/s00280-019-03885-4

Cited by 19 publications

(18 citation statements)

References 21 publications

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“…Since approval of durvalumab from the European Medicines Agency (EMA) in September 2018, twenty-six consecutive patients with PD-L1 expressing unresectable stage III – IVA NSCLC were treated and included in the analysis. Based on tumor characteristics including the UICC stage and high PTV volumes, our patient cohort is at high risk of treatment-related toxicity [ 12 , 13 ]. Nevertheless, after objective evaluation of response with contrast-enhanced CT thorax/abdomen after completion of CRT, all patients started durvalumab maintenance therapy.…”

Section: Discussionmentioning

confidence: 99%

Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients

et al. 2021

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SummaryThe aim of this prospective study is to evaluate the clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in unresectable stage, locally advanced non-small cell lung cancer (NSCLC). All consecutive patients with unresectable, locally advanced NSCLC and PD-L1 expression (≥1%) treated after October 2018 were included. Regular follow up, including physical examination, PET/CT and/or contrast-enhanced CT-Thorax/Abdomen were performed every three months after CRT. Descriptive treatment pattern analyses, including reasons of discontinuation and salvage treatment, were undertaken. Statistics were calculated from the last day of thoracic irradiation (TRT). Twenty-six patients were included. Median follow up achieved 20.6 months (range: 1.9–30.6). Durvalumab was initiated after a median of 25 (range: 13–103) days after completion of CRT. In median 14 (range: 2–24) cycles of durvalumab were applied within 6.4 (range 1–12.7) months. Six patients (23%) are still in treatment and seven (27%) have completed treatment with 24 cycles. Maintenance treatment was discontinued in 13 (50%) patients: 4 (15%) patients developed grade 3 pneumonitis according to CTCAE v5 after a median of 3.9 (range: 0.5–11.6) months and 7 (range: 2–17) cycles of durvalumab. Four (15%) patients developed grade 2 skin toxicity. One (4%) patient has discontinued treatment due to incompliance. Six and 12- month progression-free survival (PFS) rates were 82% and 62%, median PFS was not reached. No case of hyperprogression was documented. Eight (31%) patients have relapsed during maintenance treatment after a median of 4.8 (range: 2.2–11.3) months and 11 (range: 6–17) durvalumab cycles. Two patients (9%) developed a local-regional recurrence after 14 and 17 cycles of durvalumab. Extracranial distant metastases and brain metastases as first site of failure were detected in 4 (15%) and 2 (8%) patients, respectively. Three (13%) patients presented with symptomatic relapse. Our prospective study confirmed a favourable safety profile of durvalumab maintenance treatment after completion of CRT in unresectable stage, locally advanced NSCLC in a real-world setting. In a median follow-up time of 20.6 months, durvalumab was discontinued in 27% of all patients due to progressive disease. All patients with progressive disease were eligible for second-line treatment.

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Section: Discussionmentioning

confidence: 99%

Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients

et al. 2021

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“…Recently, a retrospective analysis reported that 19 (23%) of 82 patients with stage III NSCLC, who were eligible at the initiation of chemoradiotherapy, became ineligible after chemoradiotherapy according to the registered criteria of PACIFIC trial, and old age, male gender and radiation therapy with the volume of the lung that received more than 20 Gy (V20), more than 35% were closely related to the ineligibility after chemotherapy . In their study, ineligible patients for the PACIFIC study had a trend toward shorter survival than eligible patients . Sakaguchi et al .…”

Section: Introductionmentioning

confidence: 99%

Chemoradiotherapy followed by durvalumab in patients with unresectable advanced non‐small cell lung cancer: Management of adverse events

et al. 2020

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Background: Chemoradiotherapy followed by durvalumab is the standard treatment for the patients with local advanced non-small cell lung cancer (NSCLC). There is a real-world data about the management of adverse events, such as pneumonitis, according to the different institutions. Here, we present the experience regarding the management of adverse events after the initiation of durvalumab as daily practice. Methods: From July 2018 to August 2019, 41 patients with locally advanced NSCLC, who underwent chemoradiotherapy followed by durvalumab, were retrospectively analyzed in the study using our medical records. Results: The median age of patients was 72 years (range: 51-80 years). A total of 33 patients were male and eight were female, and 40 patients (98%) received a total radiation dose of 60 Gy as concomitant chemoradiotherapy. The median V20 for the entire cohort was 18.9% (range: 3.5-29.9). Any adverse events during chemoradiotherapy and durvalumab were observed in 36 patients (87.8%), while three patients (7.3%) experienced grade 3 toxicities. In total, 25 (61.0%) patients experienced pneumonitis, four (9.8%) thyroid dysfunction, three (7.3%) myopathy, two (4.9%) rash or eruption, one (2.4%) bowel disease and one (2.4%) malaise. Grade 3 pneumonitis, thyroid dysfunction and myopathy were observed in one (2.4%), one (2.4%) and one (2.4%), respectively. A total of 22 (53.7%) patients were unable to continue durvalumab due to pneumonitis. However, durvalumab was finally readministered to six patients. Conclusions: The adherence to lung dose constraints such as V20 as well as close treatment monitoring are a prerequisite for the management of pneumonitis during maintenance therapy with durvalumab.

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“…The results show that one in four patients treated with CCRT was not eligible for consolidation durvalumab. In previous studies, 23–55% of patients with unresectable stage III NSCLC did not meet the criteria of the PACIFIC trial [ 11 , 12 , 13 , 14 ]. The treatment was discontinued earlier than the planned 12 months in 55% of patients; this was consistent with the results of the PACIFIC study (51%) [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture

Kubo

Kobayashi²,

Iwanaga

et al. 2021

Journal of Radiation Research

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The promising results of the PACIFIC study led to the approval of consolidation durvalumab for coverage by the National Health Insurance (NHI) in 2018 for patients with locally-advanced unresectable non-small cell lung carcinoma (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT). However, the effect of NHI coverage on the patterns of care for this population remains unclear. Here, we conducted a questionnaire-based survey to determine the patterns of care for patients with stage II–III NSCLC treated with definitive radiotherapy in 2017 (pre-durvalumab era) or in 2019 (post-durvalumab era). Data were obtained from 11 radiotherapy facilities in Gunma prefecture, which has a population of 1.94 million. We identified 80 and 83 patients with stage II–III NSCLC who received definitive radiotherapy in Gunma in 2017 and 2019, respectively. At a given facility, CCRT was the treatment of choice in a significantly greater proportion of patients in 2019 than in 2017 (66% ± 20% vs 51% ± 29%, P = 0.041). Intensity-modulated radiotherapy (IMRT) was more frequent in 2019 than in 2017 (24% vs 1.2%). Carboplatin plus paclitaxel was used for CCRT at higher rate in 2019 than in 2017 (73% vs 44%). Consolidation durvalumab was performed in 73% (40/55) of CCRT-treated patients in 2019, and the treatment was performed for the planned 12 months in 45% (18/40) of patients. These data indicate that NHI coverage of durvalumab might be a possible reason for choosing CCRT in patients with stage II–III NSCLC in the real-world setting.

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Ineligibility for the PACIFIC trial in unresectable stage III non-small cell lung cancer patients

Cited by 19 publications

References 21 publications

Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients

Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients

Chemoradiotherapy followed by durvalumab in patients with unresectable advanced non‐small cell lung cancer: Management of adverse events

Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture

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