A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer

Abstract

IntroductionFor unresectable stage III non-small cell lung cancer (NSCLC), the standard therapy consists of chemoradiotherapy (CRT) followed by durvalumab maintenance for responding patients. The present study reports on the safety and outcome of durvalumab use after CRT in a real-world, multicenter, retrospective cohort.MethodsTwo hundred thirty-eight patients have been included. We collected data on systemic therapy, radiation therapy, the timing between CRT and durvalumab, number of durvalumab cycles, reasons for non-starting or discontinuation, incidence and grade of adverse events (AEs), and progression-free survival (PFS) and overall survival (OS).ResultsOne hundred fifty-five patients out of 238 (65.1%) received at least one durvalumab dose: 91 (58.7%) after concomitant CRT (cCRT) and 64 (41.3%) after sequential CRT (sCRT). Programmed-death ligand 1 (PD-L1) status was unknown in 7/155 (4.5%), negative in 14 (9.1%), and positive ≥1% in 134/155 (86.4%). The main reasons for non-starting durvalumab were progression (10.1%), PD-L1 negativity (7.5%), and lung toxicity (4.6%). Median follow-up time was 14 months (range 2–29); 1-year PFS and OS were 83.5% (95%CI: 77.6–89.7) and 97.2% (95%CI: 94.6–99.9), respectively. No significant differences in PFS or OS were detected for cCRT vs. sCRT, but the median PFS was 13.5 months for sCRT vs. 23 months for cCRT. Potentially immune-related AEs were recorded in 76/155 patients (49.0%). Pneumonitis was the most frequent, leading to discontinuation in 11/155 patients (7.1%).ConclusionsDurvalumab maintenenace after concurrent or sequential chemoradiation for unresectable, stage III NSCLC showed very promising short-term survival results in a large, multicenter, restrospective, real-world study. Durvalumab was the first drug obtaining a survival benefit over CRT within the past two decades, and the present study contributes to validating its use in clinical practice.

Stereotactic Body Radiation Therapy (SBRT) for Oligorecurrent/Oligoprogressive Mediastinal and Hilar Lymph Node Metastasis: A Systematic Review

“…This study also showed the need to be cautious in the reirradiation of stage 7 lymph nodes due to the risk of lethal toxicity (three patients) in consideration of the risk of necrosis or fistula of the airways, as also described in a case report [ 46 ].…”

Treatment Characteristics and Real-World Progression-Free Survival in Patients With Unresectable Stage III NSCLC Who Received Durvalumab After Chemoradiotherapy: Findings From the PACIFIC-R Study

“…14,15,28 The outcomes from PACIFIC-R align with other realworld studies of the PACIFIC regimen. [29][30][31][32][33] For instance, Taugner et al 30 reported a rwPFS rate of 62% at 12 months with durvalumab in their prospective study, which is consistent with the corresponding rate from PACIFIC-R. Moreover, outcomes for most of the analyzed subgroups from PACIFIC-R compare favorably with patients who received CRT alone in the preimmunotherapy era 25,34 ; in the international KINDLE study, median rwPFS was 12.1 and 10.4 months with cCRT and sCRT (without consolidation immunotherapy), respectively, among patients with unresectable, stage III NSCLC (acknowledging that the index date was the date of initial diagnosis for KINDLE, whereas it was the date that durvalumab was started within the EAP [i.e., post-CRT] in PACIFIC-R).…”

Oligorecurrent Non-Small-Cell Lung Cancer Treated by Chemo-Radiation Followed by Immunotherapy and Intracranial Radiosurgery: A Case Report and Mini Review of Literature

“…Recently, the results of a phase III randomized Pacific trial on patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) submitted to chemoradiotherapy (CHT-RT) followed by consolidative immunotherapy (IO) confirmed a significant benefit in terms of long-term clinical outcomes, as reported in the update analysis from Spiegel et al [1]. Furthermore, several observational studies involving large populations obtained similar results in real-world settings underlying the crucial role of this new multimodal approach in stage III NSCLC patients who have not progressed after radical chemotherapy (CHT) and radiotherapy (RT) [2]. Five-year survival outcomes from the Pacific trial showed a median overall survival (OS) and progression free survival (PFS) equal to 47.5 and 16.9 months, respectively, but, unfortunately, 6.3% of the patients developed brain metastasis during or after the consolidation phase with durvalumab [3].…”