For 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.
Two 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).
One 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 65.5% (95%CI: 57.6-74.4) and 87.9% (95%CI: 82.26.6-93.9), 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%).
Durvalumab 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.
The advent of immune checkpoint inhibitors for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) has revolutionized the standard of care approach in first-line treatment. The ...heterogeneity of disease presentation and treatment-related toxicities can be associated with suboptimal patient compliance to oncologic care. Hence, prioritizing quality of life and well-being are crucial aspects to be considered in tailoring the best treatment choice. The aim of our work is to present a short report on the topic of the patient’s preference in regard to treatment and its consequences on quality of life in the recurrent/metastatic setting. According to the literature, there’s an unmet need on how to assess patient attitude in respect to the choice of treatment. In view of the availability of different therapeutic strategies in first-line management of RM-HNSCC, increasing emphasis should be put on integrating patient preferences into the medical decision-making.
Introduction
Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant ...immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach.
Aims
A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC
Materials and methods
The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3–G4 toxicity, late pulmonary toxicity G3–G4, and acute esophageal toxicity G3–G4.
Results
The probability of OS and G3–G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms.
Conclusions
The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients.
Background and purpose
COVID-19 constitutes a worldwide threat, prompting Italian Government to implement specific measures on March 8, 2020, to protect patients and health workers from disease ...transmission. The impact of preventive measures on daily activity of a radiotherapy facility may hamper the ability to fulfill normal workload burden. Thus, we assessed the number of delivered treatments in a specific observation period after the adoption of preventive measures (since March 11 to April 24, 2020) and compared it with the corresponding period of the year 2019.
Materials and methods
Overall number of delivered fractions was related to actual time of platform daily activity and reported as a ratio between number of delivered fractions and activity hours (Fr/Hrs). Fr/Hrs were calculated and compared for two different periods of time, March 11–April 24, 2019 (Fr/Hrs1), and March 11–April 24, 2020 (Fr/Hrs2).
Results
Fr/Hrs1 and Fr/Hrs2 were 2.66 and 2.54 for year 2019 and 2020, respectively, for a Fr/Hrs
ratio
of 1.07 (95% CI 1.03–1.12,
p
= 0.0005). Fr/Hrs1 was significantly higher than Fr/Hrs2 for Sli
R
and Precise
R
, with Fr/Hrs
ratio
of 1.92 (95% CI 1.66–2.23,
p
< 0.0001) and 1.11 (95% CI 1.03–1.2,
p
= 0.003), respectively. No significant difference was reported for Synergy
R
and Cyberknife
R
with Fr/Hrs
ratio
of 0.99 (95% CI 0.91–1.08,
p
= 0.8) and 0.9 (95% CI 0.77–1.06,
p
= 0.2), respectively. Fr/Hrs1 was significantly lower than Fr/Hrs2 for Tomotherapy
R
, with Fr/Hrs
ratio
of 0.88 (95% CI 0.8–0.96,
p
= 0.007).
Conclusion
Preventive measures did not influence workload burden performed. Automation in treatment delivery seems to compensate effectively for health workers number reduction.
Purpose
Cisplatin-based chemoradiotherapy (CRT) is standard treatment for head and neck squamous cell carcinoma (HNSCC). However, IMRT may increase chemotherapy-induced nausea and vomiting (CINV). ...The purpose of this study is to investigate the effect of fosaprepitant in preventing CINV.
Methods
An infusion of 150 mg fosaprepitant was given through a 30 min. We assessed acute toxicity using CTCAE v.4 and the incidence of CINV using the FLIE questionnaire. The evaluation of CINV was done at the second and fifth weeks of CRT and 1 week after the end. The EORTC QLQ-HN 43 questionnaire was administered before treatment beginning (baseline), at second (T1) and fifth (T2) weeks. A dosimetric analysis was performed on dorsal nucleus of vagus (DVC) and area postrema (AP).
Results
Between March and November 2020, 24 patients were enrolled. No correlation was found between nausea and DVC mean dose (
p
= 0.573), and AP mean dose (
p
= 0.869). Based on the FLIE questionnaire, patients reported a mean score of 30.5 for nausea and 30 for vomiting during week 2 and 29.8 for nausea and 29.2 for vomiting during week 5. After treatment ended, the mean scores were 27.4 for nausea and 27.7 for vomiting. All patients completed the EORTC QLQ-HN 43. Significantly higher scores at T2 assessment than baseline were observed.
Conclusions
The use of fosaprepitant in preventing CINV reduced incidence of moderate to severe nausea and vomiting. No correlation has been found between nausea and median dose to DVC and AP.
The landscape of systemic therapies for advanced non-melanoma skin cancers has been revolutionized by the advent of immunotherapy. Cemiplimab is the only immune checkpoint inhibitor (ICI) approved by ...the European Medicine Agency for recurrent/metastatic cutaneous squamous cell carcinoma (cSCC). Its excellent efficacy outcomes are achieved due to its good tolerability profile. The drug-related hypersensitivity reaction (HSR) is a well-known issue in oncology, but it is rarely reported in respect to immune checkpoint inhibitors. Cemiplimab is among the agents with the best infusion tolerability profiles. Clinical practice guidelines in this field are lacking.
We report on the successful management of a severe infusion reaction induced by Cemiplimab in a patient with cSCC based on a desensitization protocol, which led to adequate treatment delivery and prolonged clinical benefit. A review of the available literature on HSR rates and its management with ICIs, and on drug desensitization (DD) protocols and their efficacy, was conducted to highlight the limited knowledge on this topic and its importance.
Our experience highlights the need for a DD protocol in order to improve the treatment of HSRs, particularly when elicited by an immunotherapy agent, preventing treatment discontinuation and preserving its efficacy.
In advanced non-small-cell lung cancer, without activating mutations and with PD-L1≥50%, Pembrolizumab monotherapy is the therapeutic standard in Europe.
To evaluate retrospectively the safety and ...efficacy of this drug and to investigate potential prognostic factors in daily clinical practice.
From September 2017 to September 2019, 205 consecutive patients from 14 Italian Medical Oncology Units were enrolled in the study. Gender, Age (> or <70 years), ECOG-PS (0-1 or 2), histology (squamous or nonsquamous), presence of brain, bone and liver metastases at baseline, PD-L1 score (>90% or <90%), smoking status (never or former or current) were applied to the stratified log-rank. Cox's proportional hazards model was used for multivariate analysis.
At a median follow-up of 15.2 months, median progression-free and overall survival (mPFS and mOS) were 9.2 months (95% C.I., 4.8-13.5) and 15.9 months (95% C.I., not yet evaluable), respectively. Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 had mPFS of 2.8 months (95% C.I., 2.1-3.4) and mOS of 3.9 months (95% C.I., 2.5-5.3). Patients with liver metastases at diagnosis had an mPFS of 3.2 months (95% C.I., 0.6-5.8) and an mOS of 6.0 months (95% C.I., 3.7-8.4). At multivariate analysis for OS gender, ECOG-PS 2, and presence of liver metastases were independent prognostic factors.
Patients with ECOG-PS 2 derived little benefit from the use of first-line pembrolizumab. In patients with liver metastases, the association of pembrolizumab with platinum-based chemotherapy could be a better option than pembrolizumab alone.
Abstract
Background
tumor recurrence after NSCLC surgical resection is the most common cause of treatment failure that sharply reduces the patient’s life expectancy. The optimal treatment strategy ...for loco-regional recurrences developing after surgical resection in patients with non–small-cell lung cancer (NSCLC) is not established yet.
This report aims to describe the pattern of relapse, PFS, and OS in patients treated with radio-chemotherapy and durvalumab for loco-regional relapse after surgery.
Methods
We conducted a multicenter, retrospective study including subjects who underwent surgical resection for NSCLC and were treated with Pacific protocol after loco-regional relapse.
Results
Twenty-four patients met the inclusion criteria. At the time of diagnosis mean age was 65 years (range 47–78), the majority being male (58.3%). The 12-month progression-free survival rate was 68.7%, the 18-month progression-free survival rate was 45.8%, and the 24-month progression-free survival rate was 34.3%. There were three deaths: the 12-month survival rate was 91%, and the 18-month survival rate was 82.8%.
Conclusions
In this article, we propose a treatment strategy that might prolong post recurrence survival in patients with good performance status experiencing loco-regional relapse after surgery.
Chemoradiation therapy (CRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD1) axis inhibitors ...with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CRT on tumor cells programmed cell death ligand-1 (PD-L1) expression is unknown.
In this multicentric retrospective study, we analyzed paired NSCLC specimens that had been obtained pre- and post-CRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. The purpose of this study was to evaluate the feasibility, risk of complications, and clinical relevance of performing re-biopsy after CRT in patients with PD-L1 negative LA-NSCLC.
Overall, 31 patients from 6 centers with PD-L1 negative LA-NSCLC were analyzed. The percentage of tumor cells with PD-L1 expression significantly increased between pre- and post-CRT specimens in 14 patients (45%). Nine patients had unchanged PD-L1 expression after CRT, in five patients the rebiopsy material was insufficient for PD-L1 analysis and in two patients no tumor cells at rebiopsy were found. The post-rebiopsy complication rate was very low (6%). All patients with positive PD-L1 re-biopsy received Durvalumab maintenance after CRT, except one patient who had a long hospitalization for tuberculosis reactivation. Median PFS of patients with unchanged or increased PD-L1 expression was 10 and 16.9 months, respectively.
CRT administration can induce PD-L1 expression in a considerable fraction of PD-L1 negative patients at baseline, allowing them receiving the maintenance Durvalumab in Europe. Hence, after a definitive CRT, PD-L1 redetermination should be considered in patients with LA-NSCLC PD-L1 negative, to have a better selection of maintenance Durvalumab candidates.
Choroidal localization from non-small cell lung cancer is rare and when it occurs may cause visual alterations. Targeted therapy against actionable gene mutations represents the standard of care in ...advanced non-small cell lung cancer. We report the case of a 53-year-old woman affected by metastatic anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer who received ALK tyrosine kinase inhibitors, from January 2017. The patient had a complete response of choroidal metastasis after therapy with ALK tyrosine kinase inhibitors. She recovered a complete visus and actually she still continue therapy with alectinib. The patient had a complete recovery of visus in addiction to a long response on treatment.
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