Clinical outcomes in stage III non-small cell lung cancer patients treated with durvalumab after sequential or concurrent platinum-based chemoradiotherapy – single institute experience

Abstract

Background Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the usage of gemcitabine. Patients and methods We retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treatment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients. Results Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during concurrent treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%). Conclusions Our survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.

Chemoradiation followed by adjuvant durvalumab in stage III non–small cell lung cancer: Real‐world comparison of treatment outcomes to historical controls treated with chemoradiation alone

“…The results of this single institution retrospective analysis demonstrate that for patients with locally advanced stage III NSCLC, the use of adjuvant durvalumab after completion of chemoradiation improves PFS and OS compared to historic controls treated with chemoradiation alone. Although most patients in our trial did not conform to eligibility criteria for inclusion in the PACIFIC trial because of delay in starting adjuvant durvalumab ( n = 51), history of immune disease ( n = 3), or ECOG status ≥2 ( n = 4), the improved PFS and OS with adjuvant durvalumab observed in our study are consistent with outcomes reported in the PACIFIC trial and other real‐world studies 7–18 . The real‐world data presented in this study, although limited, suggest that future clinical trials consider inclusion of patients who begin durvalumab therapy beyond 42 days after completion of chemoradiation, have a prior history of immune disease, or have an ECOG performance status ≥2.…”

“…Although most patients in our trial did not conform to eligibility criteria for inclusion in the PACIFIC trial because of delay in starting adjuvant durvalumab (n = 51), history of immune disease (n = 3), or ECOG status ≥2 (n = 4), the improved PFS and OS with adjuvant durvalumab observed in our study are consistent with outcomes reported in the PACIFIC trial and other real-world studies. [7][8][9][10][11][12][13][14][15][16][17][18] The real-world data presented in this study, although limited, suggest that future clinical trials consider inclusion of patients who begin durvalumab therapy beyond 42 days after completion of chemoradiation, have a prior history of immune disease, or have an ECOG performance status ≥2.…”

“…The PACIFIC trial reported improved outcomes in carefully selected patients with unresectable stage III NSCLC treated with 1 year of adjuvant durvalumab following chemoradiation compared to a control group treated with chemoradiation followed by placebo 7–11 . Subsequent reports from real‐world single and multicenter studies confirmed the improved OS and PFS reported in the PACIFIC trial 12–18 . As a result, consolidation of treatment with 1 year of adjuvant durvalumab has become the new standard of care for stage III unresectable NSCLC 19,20 .…”

“… 7 , 8 , 9 , 10 , 11 Subsequent reports from real‐world single and multicenter studies confirmed the improved OS and PFS reported in the PACIFIC trial. 12 , 13 , 14 , 15 , 16 , 17 , 18 As a result, consolidation of treatment with 1 year of adjuvant durvalumab has become the new standard of care for stage III unresectable NSCLC. 19 , 20 Since the publication of the PACIFIC trial, our institution offered treatment with adjuvant durvalumab to all patients with unresectable stage III NSCLC without disease progression following chemoradiation.…”

The spine and carina as a surrogate for target registration in cone-beam CT imaging verification in locally advanced lung cancer radiotherapy

“… 1 But still, nearly half of the patients will experience locoregional relapse. 2 The accuracy of different steps in radiotherapy treatment preparation and execution have a strong impact on local control. 3 With the introductionof computed tomography (CT), positron emission computed tomography (PET CT) and four-dimensional (4D) CT simulation, the target delineation accuracy increased.…”