Patients with unresectable stage III non-small cell lung cancer eligible to receive consolidation therapy with durvalumab in clinical practice based on PACIFIC study criteria

Sakaguchi, Tadashi; Ito, Kentaro; Furuhashi, Kazuki; Nakamura, Yuki; Suzuki, Yuta; Nishii, Yoichi; Taguchi, Osamu; Hataji, Osamu

doi:10.1016/j.resinv.2019.03.011

Cited by 33 publications

(31 citation statements)

References 8 publications

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“…A well-researched systematic review demonstrated a rate of severe pneumonitis defined by CTCAE ≥ 3 due to platinum-based CRT of 9%-12% (13). A study that investigated durvalumab eligibility in 81 patients reported a pneumonitis rate CTCAE ≥ 2 of 16% within 6 weeks after finishing platinum-based CRT (5). These data demonstrate that the definition of therapy-related significant pneumonitis differs in severity and timing.…”

Section: Discussionmentioning

confidence: 92%

“…In the recently treated subgroup with PD-L1 expression results available, this ratio was 72%, considering the additional requirement of a minimum 1% PD-L1 expression. Compared to that, a study that analyzed data of 81 patients from January 2011 to May 2018 published an eligibility rate of approximately 70% without considering PD-L1 expression levels (5).…”

Section: Discussionmentioning

confidence: 99%

“…The characteristics of this highly selected patient collective are arguably discordant with the perceived clinical reality of stage III NSCLC patients, as a small retrospective analysis recently demonstrated. It reports that merely two thirds of the 73 patients included were eligible for CIT according to the three-criteria disease progression, therapy-related toxicity, and WHO performance status (5). Nevertheless, due to the small size of the analyzed patient collective the few criteria investigated and the purely descriptive nature of the analysis, reliable data on subject of CIT eligibility is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer—Cross-Sectional Study of Eligibility and Administration Rates

et al. 2020

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IntroductionThe PACIFC trial demonstrated a significant benefit of durvalumab consolidation immunotherapy (CIT) after definitive platinum-based chemoradiotherapy (P-CRT) for survival in stage III non-small cell lung cancer (NSCLC). It is unknown how many patients are eligible in clinical practice to receive CIT according to PACIFIC criteria compared to real administration rates and what influencing factors are.Patients and MethodsWe analyzed 442 patients with unresectable stage III NSCLC who received P-CRT between 2009 and 2019 regarding CIT eligibility rates according to PACIFIC criteria and administration rates since drug approval.ResultsSixty-four percent of 437 patients were male, median age was 63 years [interquartile range (IQR): 57–69]. The most common histologic subtypes were adenocarcinoma (42.8%) and squamous cell carcinoma (41.1%), most tumors were in stage IIIB (56.8%). Mean PD-L1 tumor proportion score (TPS) was 29.8% (IQR: 1–60). The median total RT dose was 60 Gy (IQR: 60–66). Platinum component of P-CRT was evenly distributed between cisplatin (51.4%) and carboplatin (48.6%). 50.3% of patients were eligible for CIT according to PACIFIC criteria. Observed contraindications were progressive disease according to RECIST (32.4%), followed by a PD-L1 TPS < 1% (22.3%), pneumonitis CTCAE ≥ 2 (12.6%) and others (4.9%). One year after drug approval, 85.6% of patients who were eligible according to PACIFIC criteria actually received CIT. Time interval between chemotherapy start and radiation therapy start (OR 0.9, 95% CI: [0.9; 1.0] p = 0.009) and probably cisplatin as platinum-component of P-CRT (OR 1.5, 95% CI: [1.0; 2.4] p < 0.061) influence CIT eligibility. Highly positive PD-L1 TPS (≥50%; (OR 2.4, 95% CI: [1.3; 4.5] p = 0.004) was associated to a better chance for CIT eligibility.ConclusionEighty-five percent of potentially eligible patients received CIT one year after drug approval. Fifty percent of patients did not meet PACIFIC criteria for durvalumab eligibility, this was mainly caused by disease progression during platinum-based CRT, followed by therapy-related pneumonitis and PD-L1 TPS < 1% (in view of the EMA drug approval).

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer—Cross-Sectional Study of Eligibility and Administration Rates

et al. 2020

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“…Sakaguchi et al . also described a retrospective study to assess the eligibility of patients with unresectable stage III NSCLC who were able to receive durvalumab after chemoradiotherapy based on the PACIFIC trial criteria . In their study, radiation pneumonitis of any grade and grade 2 or more occurred in 54 (73.9%) and 12 (16.4%) of 73 patients after chemoradiotherapy, respectively.…”

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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“…Currently, published data regarding eligibility criteria in real-life clinical practice area limited; however, a few retrospective, single-center studies have specifically assessed these criteria. Sakaguchi et al [ 32 ] evaluated the clinical criteria for durvalumab after CRT in an historical cohort of 73 patients with unresectable stage III NSCLC based on the eligibility criteria established in the PACIFIC trial. This patient cohort was treated between 2011 and 2018 and approximately 30% did not meet eligibility criteria for durvalumab therapy.…”

Section: Which Patients Should Be Included or Excluded From The Pacifmentioning

confidence: 99%

Deep diving in the PACIFIC: Practical issues in stage III non-small cell lung cancer to avoid shipwreck

Mielgo-Rubio¹,

Rojo²,

Mezquita-Pérez³

et al. 2020

WJCO

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After publication of the PACIFIC trial results, immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer (NSCLC). The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC. This is the first treatment in decades to successfully improve survival in this clinical setting, with manageable toxicity and without deterioration in quality of life. The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary, coordinated decision-making among lung cancer specialists, bringing new challenges and controversies as well as important changes in clinical work routines. The aim of the present article is to review—from a practical, multidisciplinary perspective—the findings and implications of the PACIFIC trial. We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination. In addition, we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice. Finally, we discuss unresolved questions and future challenges. In short, the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.

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Patients with unresectable stage III non-small cell lung cancer eligible to receive consolidation therapy with durvalumab in clinical practice based on PACIFIC study criteria

Cited by 33 publications

References 8 publications

Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer—Cross-Sectional Study of Eligibility and Administration Rates

Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer—Cross-Sectional Study of Eligibility and Administration Rates

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

Deep diving in the PACIFIC: Practical issues in stage III non-small cell lung cancer to avoid shipwreck

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