Safety and feasibility of consolidation pembrolizumab following concurrent chemoradiation for unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN14-179.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8523-8523 ◽  
Author(s):  
Greg Andrew Durm ◽  
Cynthia Johnson ◽  
Shadia Ibrahim Jalal ◽  
Ahad Ali Sadiq ◽  
Salma Jabbour ◽  
...  
Keyword(s):  
Early Report ◽  
Safety Data ◽  
Standard Of Care ◽  
Research Network ◽  
Stage Iii ◽  
Unresectable Stage ◽  
Metastatic Setting ◽  
Increased Risk ◽  
Stage Iii Nsclc ◽  
Grade 3

8523 Background: The standard of care for unresectable stage III NSCLC is concurrent chemorad. Following treatment, the risk of radiation pneumonitis is greatest at 1-3 mo. Pneumonitis risk increases with consolidation chemotherapy. A previous trial by our group (Hanna et al, JCO 2008) of consolidation docetaxel showed 80.8% completed 3 planned cycles of chemo with a grade 3-5 pneumonitis rate of 9.6% and 1 death. PD-1 inhibitors are also associated with an increased risk of pneumonitis in the metastatic setting. We conducted a phase II trial of consolidation pembro initiated 1-2 mo after concurrent chemorad, a period during which pts are at high risk of developing pneumonitis. Methods: Pts with stage III NSCLC who completed chemorad with either carbo/paclitaxel, cis/etop, or cis/pemetrexed plus 59-66.6 Gy of radiation and had no PD received pembro 200mg IV q3wk for up to 1 yr. Primary endpoint is time to metastatic disease. The objective of the study is to evaluate both safety and efficacy, and here we report preliminary safety and feasibility results. Evaluable pts for this analysis had ≥3 mo of f/u or went off study due to PD, toxicity, or death < 3 mos after initiation of pembro. Results: 93 pts enrolled. Median age 67 (range 46-84), 59 (63.4%) were male. 87 (93.5%) were former or current smokers. 68 (73.1%) received carbo/pac, 24 (25.8%) received cis/etop, and 1 received cis/pemetrexed. SqCC (n = 41), non-SqCC (n = 43), NSCLC NOS (n = 8), mixed (n = 1). IIIA (n = 56), IIIB (n = 37). At the time of analysis, 83 of 93 pts were evaluable. 66 of 83 (79.5%) received ≥ 3 mo of pembro. 17 (20.5%) pts developed any grade pneumonitis with 14 of 17 occurring in the first 12 wks (median 9 wks). Only 3 (3.6%) pts developed grade 3-5 pneumonitis related to pembro. There was 1 pneumonitis-related death and a second death from respiratory failure possibly related to pembro. Conclusions: This early report indicates that most patients can safely receive consolidation pembro within 1-2 mo of completing chemorad. The incidence of serious pneumonitis during the first 3 mo of treatment appears low. Updated safety data on all 93 pts will be presented at the ASCO meeting. Clinical trial information: NCT02343952.

Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: An update from the PACIFIC trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8511-8511
Author(s):  
David R. Spigel ◽  
Corinne Faivre-Finn ◽  
Jhanelle Elaine Gray ◽  
David Vicente ◽  
David Planchard ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Stage Iii ◽  
Smoking History ◽  
Kaplan Meier ◽  
Unresectable Stage ◽  
The Pacific ◽  
Patient Reported ◽  
Stage Iii Nsclc

8511 Background: In the placebo-controlled Phase III PACIFIC trial of patients with unresectable Stage III NSCLC whose disease had not progressed after platinum-based concurrent chemoradiotherapy (cCRT), durvalumab improved overall survival (OS) (stratified hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.53–0.87; p=0.0025; data cutoff [DCO] Mar 22, 2018) and progression-free survival (PFS) (stratified HR 0.52, 95% CI 0.42–0.65; p<0.0001; DCO Feb 13, 2017) based on the DCOs used for the primary analyses, and the degree of benefit remained consistent in subsequent updates. Durvalumab was associated with a manageable safety profile, and did not detrimentally affect patient-reported outcomes, compared with placebo. These findings established consolidation durvalumab after CRT (the ‘PACIFIC regimen’) as the standard of care in this setting. We report updated, exploratory analyses of OS and PFS, assessed approximately 5 years after the last patient was randomized. Methods: Patients with WHO PS 0/1 (and any tumor PD-L1 status) whose disease did not progress after cCRT (≥2 overlapping cycles) were randomized (2:1) 1–42 days following cCRT (total prescription radiotherapy dose typically 60–66 Gy in 30–33 fractions) to receive 12 months’ durvalumab (10 mg/kg IV every 2 weeks) or placebo, stratified by age (<65 vs ≥65 years), sex, and smoking history (current/former smoker vs never smoked). The primary endpoints were OS and PFS (blinded independent central review; RECIST v1.1) in the intent-to-treat (ITT) population. HRs and 95% CIs were estimated using stratified log-rank tests in the ITT population. Medians and OS/PFS rates at 60 months were estimated with the Kaplan–Meier method. Results: Overall, 709/713 randomized patients received treatment in either the durvalumab (n/N=473/476) or placebo (n/N=236/237) arms. The last patient had completed study treatment in May 2017. As of Jan 11, 2021 (median follow-up duration of 34.2 months in all patients; range, 0.2–74.7 months), updated OS (stratified HR 0.72, 95% CI 0.59–0.89; median 47.5 vs 29.1 months) and PFS (stratified HR 0.55, 95% CI 0.45–0.68; median 16.9 vs 5.6 months) remained consistent with the results from the primary analyses. The 60-month OS rates were 42.9% and 33.4% with durvalumab and placebo, respectively, and 60-month PFS rates were 33.1% and 19.0%, respectively. Updated treatment effect estimates for patient subgroups will be presented. Conclusions: These updated survival analyses, based on 5-year data from PACIFIC, demonstrate robust and sustained OS plus durable PFS benefit with the PACIFIC regimen. An estimated 42.9% of patients randomized to durvalumab remain alive at 5 years and approximately a third remain both alive and free of disease progression. Clinical trial information: NCT02125461.

Safety assessment for the combination of docetaxel, carboplatin, and thoracic radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC): A report of the first 100 patients treated with chemoradiation on D0410

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7701-7701
Author(s):  
J. R. Rigas ◽  
M. S. Rubin ◽  
J. M. Waples ◽  
K. H. Dragnev ◽  
D. M. Zimmerman ◽  
...  
Keyword(s):  
Safety Information ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Stage Iii ◽  
Efficacy Evaluation ◽  
Phase Iii Trial ◽  
Total Lung Volume ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

7701 Background: Concurrent chemoradiotherapy (chemoRT) is the preferred treatment for patients with unresectable stage III NSCLC. Limited safety information is available on the use of concurrent docetaxel, carboplatin and thoracic RT. We report the safety information on the initial 100 patients (pts) treated with this chemoRT as part of an ongoing US randomized phase III trial (D0410) evaluating the role of erlotinib/placebo following this concurrent chemoRT treatment. The sample size is 400 pts and the primary endpoint is progression-free survival. Methods: Pts with unresectable pathologically confirmed stage III NSCLC are randomized to receive either erlotinib 150 mg or placebo orally daily for 2 years following concurrent chemoRT with docetaxel 20 mg/m2, carboplatin AUC=2 intravenously weekly for 6 wks with thoracic RT of at least 61 Gy in 33 fractions over 6.5 weeks. The planned total lung volume exceeding 20 Gy (V20) was less than 32%. Only the chemoradiation safety information is being reported. This data was reviewed by an independent safety and data monitoring committee. Results: Pt characteristics; 59% males, median age 69 years (range 38 to 86), 21% adenocarcinoma, 48% squamous cell, 94% ECOG PS0–1, 49% stage IIIA, 15% weight loss = 10%. Of 600 planned chemotherapy treatments, 492 were administered (93 wk 1, 85 wk 2, 82 wk 3, 81 wk 4, 77 wk 5, 74 wk 6). There were 25 chemotherapy dose reductions; most commonly for esophagitis (8), neutropenia (5), renal dysfunction (3), hypersensitivity (2). There were no treatment-related deaths. There were 25 grade 3 and 3 grade 4 treatment-related adverse events. The most common grade 3/4 events were esophagitis (6), fatigue (3), odynophagia (2), neutropenia (1), thrombocytopenia (1), dematitis (1). Conclusions: This concurrent chemoradiation regimen appears to be safe. Enrollment to the phase III trial continues. There is a planned interim efficacy evaluation at 150 events (deaths or disease progression). Funded in part by Sanofi- Aventis, Genentech, and OSI Pharmaceuticals. [Table: see text]

Phase II study of TS-1 (S) plus cisplatin (P) with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18070-18070
Author(s):  
F. Ohyanagi ◽  
N. Yamamoto ◽  
A. Horiike ◽  
T. Horai ◽  
K. Gomi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Fourth Generation ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

18070 Background: Although combined chemoradiotherapy is the standard of care in stage III NSCLC, the optimal chemotherapy regimen is not established. S-1, a fourth-generation oral fluoropyrimidine is an active new agent for NSCLC and the combination with cisplatin has a favorable toxicity profile. The objective of this study was to evaluate feasibility and efficacy of S plus P with concurrent radiation for unresectable stage III NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC, 20 to 75 years in age, performance status 0–1, with no prior chemotherapy were eligible for the study. Patients were treated with P (60 mg/m2 on day 1) and S (orally at 40 mg/m2/dose bid (80 mg/m2/d), on days 1 to 14) repeated every 3–4 weeks for 4 cycles and TRT (60 Gy/30 fr over 6 weeks starting on day 2). The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 28 patients (Simon’s two-stage minimax design, P0=70%, P1=90%, a =0.1, β = 0.1). Results: Of 28 patients enrolled between August 2005 and October 2006, 28 were evaluable. There were 24 males and 4 females, median age of 63 (range 40–74) and 11 IIIA and 17 IIIB. Chemoradiotherapy was well tolerated; 2 cycles of SP and 60 Gy of TRT were administered in all patients and 24 (86%) patients received 4 cycles of SP. During concurrent chemoradiotherapy, grade 3 toxicities were neutropenia (8 pts), leukopenia (6 pts), fatigue (6 pts), anorexia (5 pts), febrile neutropenia (4 pts) and, esophagitis (4 pts). Only one grade 4 leukopenia were observed. During consolidation therapy, grade 3–4 neutropenia, anemia, esophagitis, and pneumonitis were developed in 4, 1, 1 and 2 patients, respectively. No toxic deaths have occurred. Overall RR was 85.7% (95% CI: 79.1- 98.7%) with 4 SDs and 24 PRs. The median progression-free survival and median survival is not mature enough to estimate as only 4 progression and no deaths have occurred. Conclusions: This chemoradiotherapy regimen produced promising response rate in patients with stage III NSCLC and it seems to be well-tolerated. No significant financial relationships to disclose.

Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel (PC) or cisplatin/etoposide (PE) in stage III non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18559-e18559
Author(s):  
Mun Sem Liew ◽  
Joseph Sia ◽  
Samuel John Harris ◽  
Alireza Tafreshi ◽  
Maud HW Starmans ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Concurrent Chemotherapy ◽  
Stage Iii ◽  
Hematological Toxicity ◽  
Unresectable Stage ◽  
Treatment Type ◽  
Stage Iii Nsclc ◽  
Similar Survival ◽  
Austin Health ◽  
Age Range

e18559 Background: Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients (pts) with unresectable stage III NSCLC. Although 60Gy of radiotherapy is accepted as the standard radiation dose, the concurrent chemotherapy regimen is idiosyncratic to the institution with PC generally reserved for older and less fit pts. We retrospectively reviewed outcomes and toxicity of two widely used regimens at our institution (Austin Health, Melbourne): weekly PC (Belani et al, 2005) versus (vs) PE given weeks 1 and 5 (SWOG 9019) each with concurrent chest radiotherapy. Methods: Charts from stage III NSCLC pts treated with radical dose CCRT between 2000-2011 were reviewed. Clinical data including demographics, toxicity, and response were reviewed. Results: A total of 83 (PC: 50, PE: 33) pts were treated. PC pts were older [median age (range) 70 year (44-83) vs 63 year (32-76); p=0.001]. Other characteristics were comparable in PC and PE groups (Table). Increased grade (gr) ≥3 neutropenia was seen with PE (39% vs 12%, p=0.008). Other gr ≥3 toxicities were similar including febrile neutropenia, esophagitis and pneumonitis. With a median follow up of 17.2 months (mo), no statistical difference in overall survival (OS) (median PC 21.3 mo vs PE 13.7 mo; p=0.690) and relapse free survival (median PC 12.0 mo vs PE 11.1 mo; p=0.934) were observed. In multivariate analysis, where treatment type and age were included in the model, only more advanced stage predicted poorer OS (p=0.045). Conclusions: PC was more likely to be used in elderly pts. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes compared to PE. PC is an acceptable CCRT regimen especially in older pts. [Table: see text]

Phase I study of concurrent high-dose three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7546-7546
Author(s):  
I. Sekine ◽  
M. Sumi ◽  
Y. Ito ◽  
H. Nokihara ◽  
N. Yamamoto ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Optimal Dose ◽  
Stage Iii ◽  
High Dose ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Three Dimensional Conformal Radiotherapy ◽  
3D Crt

7546 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. Methods: Eligible patients (unresectable stage III NSCLC, age ≥ 20 years, PS 0–1, V20 ≤ 30%) received cisplatin (80mg/m2 day 1) and vinorelbine (20mg/m2 days 1 and 8) repeated every 4 weeks for 3–4 cycles. The dose of 3D-CRT was 66 Gy in 33 fractions, 72 Gy in 36 fractions, and 78 Gy in 39 fractions at levels 1–3, respectively. The dose-limiting toxicity (DLT), defined as grade ≥3 esophagitis, pneumonitis, myelitis, dermatitis and heart injury, and early stop of protocol treatment, was evaluated in 6–12 patients at each level. Results: Of the 17, 16 and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled into levels 1–3, respectively, of the study. A total of 26 patients were excluded because of V20 > 30% (n=10), overdose to the esophagus (n=8) and brachial plexus (n=2), comorbidity (n=3), or patient refusal (n=3). There were 26 men and 5 women with a median (range) age of 60 (41–75) years. Of these, 23 (74%) had adenocarcinoma and 20 (65%) had stage IIIA disease. The full planned dose of radiotherapy could be administered in all the patients, and more than 80% of the patients received 3–4 cycles of chemotherapy. Grade 3–4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, grade 3 esophagitis and grade 3 pulmonary toxicity were noted in one, two and one patients, respectively. DLT was noted in 17% of the patients at each level. Two (6%) complete and 27 (87%) partial responses were obtained. In a preliminary survival analysis, the median progression-free and overall survivals were determined to be 15.0 months and 37.6 months, respectively. Conclusions: At the level of 78Gy, only 25% of the patients assessed for eligibility were actually eligible. Toxicity was relatively mild up to 78 Gy in this highly selective patient group. Thus, we determined that the recommended dose of 3D-CRT administered concurrently with cisplatin and vinorelbine chemotherapy was 72Gy. [Table: see text]

Multicenter phase II study of concurrent high-dose (72Gy) three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7070-7070 ◽  
Author(s):  
Hidehito Horinouchi ◽  
Ikuo Sekine ◽  
Minako Sumi ◽  
Miyako Satouchi ◽  
Hiroshi Isobe ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Conformal Radiotherapy ◽  
Optimal Dose ◽  
Distant Recurrence ◽  
Stage Iii ◽  
High Dose ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
3D Crt

7070 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. We previously concluded that the recommended dose for further trial was 72Gy in a phase I study (Sekine et al., Int J Radiat Oncol Biol Phys. 953-959, 2012). Methods: Eligible patients (unresectable stage III NSCLC, age between 20 and 74, PS 0-1, V20 ≤ 30%) received cisplatin (80 mg/m2 day 1) and vinorelbine (20 mg/m2 days 1 and 8) repeated every 4 weeks for 3-4 cycles. The 3D-CRT started at the first day of chemotherapy at a total dose of 72 Gy in 36 fractions. The primary endpoint was a 2-year survival rate and the planned sample size was 60 to reject the rate of 45% under the expectation of 65% with a power of 90% and an alpha error of 5%. Results: Thirty-one patients from 4 institutions were enrolled between May 2009 and March 2010. This trial was terminated early due to slow accrual and grade 5 pulmonary toxicities in 2 patients. There were 25 men and 6 women with a median (range) age of 59 (32-72) years. Of these, 23 had adenocarcinoma and 21 had stage IIIA disease. The median (range) V20 value was 20 (9-30). The full planned dose of radiotherapy could be administered in 30 (97%) patients, and 26 (84%) of the patients received 3-4 cycles of chemotherapy. During the chemoradiotherapy, grade 3-4 febrile neutropenia, infection and esophagitis were noted in 5, 4 and 1 of the 31 patients, respectively. After completion of the planned chemoradiotherapy, 5 patients had grade 3 or higher radiation pneumonitis, and 2 (6%) of these patients died at 6.6 and 7.3 months after the treatment started. The overall response rate was 97% (95% confidence interval: 83.3-99.9). Twenty-four patients are alive and thirteen patients experienced recurrence (2 had loco-regional recurrences, 7 had distant recurrence and 4 had mixed recurrence pattern) at a median follow up of 16.4 months. Conclusions: Concurrent high-dose (72Gy) 3D-CRT with chemotherapy using cisplatin and vinorelbine may have a too excessive incidence of pulmonary toxicities to warrant any further evaluation.

Non-pneumonitis immune-mediated adverse events (imAEs) with durvalumab in patients with unresectable stage III NSCLC (PACIFIC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9048-9048
Author(s):  
Jarushka Naidoo ◽  
Johan F. Vansteenkiste ◽  
Corinne Faivre-Finn ◽  
Mustafa Özgüroğlu ◽  
Shuji Murakami ◽  
...  
Keyword(s):  
Stage Iii ◽  
Smoking History ◽  
High Dose ◽  
Thyroid Disorders ◽  
Double Blind ◽  
Unresectable Stage ◽  
Baseline Factors ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Time To Onset

9048 Background: The phase 3 PACIFIC trial established durvalumab (durva) after chemoradiotherapy (CRT) as SoC for pts with unresectable stage III NSCLC. We report exploratory analyses to characterize non-pneumonitis (np) imAEs that occurred with durva in PACIFIC. Methods: PACIFIC was a double blind trial of pts without disease progression after platinum-based concurrent CRT (≥2 cycles). Pts were randomized 2:1 to receive durva 10 mg/kg or placebo (pbo) IV q2w for ≤12 months, stratified by age, sex and smoking history. We characterized the time to onset, duration, and management/outcomes of np imAEs and their association with (1) baseline pt/disease factors and (2) AEs (excluding all-cause pneumonitis). Results: Of 709 treated pts, 19% and 11% experienced imAEs and np imAEs of any grade, respectively; proportionally more had np imAEs with durva (71/475; 15%) vs pbo (5/234; 2%). Thyroid disorders (54/475; 11%), rash/dermatitis (9/475; 2%), and diarrhea/colitis (5/475; 1%) were the most common np imAEs with durva; rash/dermatitis had the shortest time to onset (Table). Among durva treated pts with np imAEs, 11% had grade 3/4 np imAEs, 41% had np imAEs that resolved, and none had fatal np imAEs; interventions included endocrine replacement therapy (73%), systemic corticosteroids (34%), high dose corticosteroids (16%), and discontinuation (10%). There were no apparent differences in baseline factors between pts with or without np imAEs. Durva had a broadly manageable safety profile irrespective of the occurrence of np imAEs. However, a higher proportion of durva treated pts with vs without np imAEs experienced all-cause, grade 3/4 events (41% vs 29%); none were fatal (excl. pneumonitis). Conclusions: Np imAEs occurred infrequently in PACIFIC, but were more common with durva vs pbo; thyroid disorders and rash/dermatitis were the most common np imAEs. Of durva treated pts with np imAEs, 11% experienced np imAEs of grade 3/4. Overall, np imAEs were broadly manageable and did not lead to high rates of discontinuation, and no association with baseline factors was seen, suggesting this should not deter use of durva in eligible pts. Clinical trial information: NCT02125461. [Table: see text]

Chemoradiation-induced pneumonitis in patients with unresectable stage III non-small cell lung cancer: A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20532-e20532
Author(s):  
Christine Pierce ◽  
Yuting Kuang ◽  
Hsiu-Ching Chang ◽  
Arianna Nevo ◽  
Anne Deitz ◽  
...  
Keyword(s):  
Observational Studies ◽  
Meta Analysis ◽  
Stage Iii ◽  
Baseline Risk ◽  
Small Cell Lung ◽  
Unresectable Stage ◽  
Immune Mediated ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Nsclc Patients

e20532 Background: Recent clinical trials have shown positive results for therapies combining concurrent chemoradiation therapy (cCRT) and checkpoint immunotherapy in unresectable non-small cell lung cancer (NSCLC). cCRT is associated with an increased risk of pneumonitis, a severe and life-threatening inflammation of the lungs. To further inform clinical decision-making and support the evaluation of new therapies combining immunotherapies with cCRT, it is important to understand the baseline risk of pneumonitis associated with cCRT alone. The objective of this study was to quantify the incidence of cCRT-induced grade 3−5 pneumonitis (immune-mediated and radiation pneumonitis) in unresectable stage III NSCLC patients. Methods: A systematic literature review and meta-analysis were performed in accordance with PRISMA guidelines. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to April 24, 2020. Chemotherapies of interest were cisplatin, pemetrexed, etoposide, carboplatin, and paclitaxel. Randomized controlled trials (RCTs), observational studies, and non-randomized trials were included. Bayesian meta-analysis using a binomial model random effects model was conducted with SAS 9.4. Results: Among 1,889 records identified from the search, 17 studies (6 RCTs, 8 observational studies, 3 single-arm trials) met inclusion criteria. Eleven studies were included in the meta-analysis (5 RCTs, 6 observational studies; 1,788 patients). All studies specified radiation-related pneumonitis (RP), although this is clinically indistinguishable from immune-mediated pneumonitis. Patient populations were comparable across studies; the most common chemotherapies were paclitaxel + carboplatin (n = 6) and pemetrexed + cisplatin (n = 5), and radiation doses ranged from 60–74 Gy. There was variation across studies in intervention, outcome reporting, and follow-up (median range: 12–73 months), but this variation was considered acceptable based on sensitivity analyses. The estimated pooled incidence of grade 3−5 RP in cCRT-treated unresectable stage III NSCLC patients was 3.62% [95% confidence interval (CI): 1.65−6.21] in RCTs and 5.98% [95% CI: 2.26−12.91] in observational studies. The pooled incidence of fatal (grade 5) RP was 0.37% [95% CI: 0−2.78] in RCTs and 1.73% [95% CI: 0.53−4.33] in observational studies. Conclusions: This study estimates that 3.62–5.98% of patients with unresectable stage III NSCLC develop grade 3−5 RP when treated with cCRT, with incidence varying by study design. Estimates of RP incidence were higher in the real-world setting compared to RCTs. These results can be used to contextualize the baseline risk of cCRT-induced pneumonitis in unresectable stage III NSCLC to better understand the adverse event of pneumonitis associated with novel immunotherapy treatments indicated for concomitant use with this modality.

Maintenance gefitinib (G) after chemoradiotherapy (CRT) in patients (pts) with unresectable stage IIIA/B non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7188-7188
Author(s):  
J. R. Gray ◽  
D. R. Spigel ◽  
J. D. Hainsworth ◽  
E. Vazquez ◽  
J. D. Peyton ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Large Cell ◽  
Research Network ◽  
Stage Iii ◽  
Stage Iiia ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Ecog Ps

7188 Background: Concurrent CRT improves outcomes for pts with unresectable stage III NSCLC compared with radiation (RT) alone. The EGFR inhibitor G benefits select pts with advanced NSCLC. This multicenter community phase II trial examined the role of CRT followed by G for pts with unresectable stage III NSCLC. Methods: Theprimary endpoint was 2-year overall survival (OS) in pts with unresectable stage IIIA/B NSCLC (effusions, N3 mediastinal nodes >4 cm excluded) treated with CRT followed by G. Induction(I) treatment (tx): docetaxel (D) 40 mg/m2 IV and gemcitabine 800 mg/m2 IV D1, 8 Q 21D × 3 cycles. Pts without progressive disease (PD) began: D 20 mg/m2 IV and carboplatin (C) AUC = 1.5 IV weekly × 6 and RT 61.2 Gy, 1.8-Gy M-F weekly × 7 (starting 1 week prior to D/C). If no PD, pts received G 250 mg PO daily × 2 years or until PD. Eligibility:measurable disease, ECOG PS 0–1, informed consent. Intent to treat analysis. Results: One-hundred three pts were enrolled from 7/03 to 4/05. Baseline features: medianage 60 years (37–79); male/female 54%/46%; ECOG PS 0/1:26%/74%; adenocarcinoma (26%), squamous (32%), large cell (28%), mixed/not specified (14%); IIIA/B (46%/54%). Grade 3/4 toxicities were limited to ≤ 8% except for neutropenia (17%, during I) - with notx-related deaths. Complete/partial responses after I were seen in 1 pt/34 pts, respectively, for an overall response rate (RR) of 34% (95% CI 26%-44%). Forty-two pts (41%) had stable disease (SD) and 12% had PD (9 pts were unevaluable.) Seventy-four pts (72%) received D/C/RT which resulted in an overall RR of 44% (95% CI 35%-54%). Fifteen percent had SD. Fifty-six pts (54%) received G for a median of 28 weeks (1–107). Median PFS and OS are 9.9 and 15 months, respectively. After a median follow-up of 19 months, actuarial 1- and 2-year progression-free survival (PFS) is 41% and 12%, respectively. 1- and 2-year OS rates are 64% and 21%, respectively. Subset analyses by smoking, gender, histology, and stage are in progress. Conclusions: Maintenance G following CRT in unresectable NSCLC does not appear to improve survival. It is possible that further analysis may suggest a role for G in selected pts. [Table: see text]

Phase III study of cisplatin (P) plus etoposide (E) with concurrent chest radiation (XRT) followed by docetaxel (D) vs. observation in patients (pts) with stage III non-small cell lung cancer (NSCLC): An interim toxicity analysis of consolidation therapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7043-7043 ◽  
Author(s):  
P. M. Bedano ◽  
M. Neubauer ◽  
R. Ansari ◽  
R. Govindan ◽  
L. H. Einhorn ◽  
...  
Keyword(s):  
High Rate ◽  
Phase Iii ◽  
Study Entry ◽  
Stage Iii ◽  
Unresectable Stage ◽  
Toxicity Analysis ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Asco Meeting ◽  
Dose Modifications

7043 Background: Concurrent chemo radiotherapy is the standard treatment for pts with unresectable stage III NSCLC. A previously reported phase II study (Gandara et al J Clin Oncol 2003) suggests that consolidation D after concurrent PE/XRT may further improve survival. HOG LUN01–24, is an ongoing phase III clinical trial comparing chemo radiation. A preliminary analysis of the differences in toxicities between PE/XRT with or without consolidation D was performed. Methods: Eligible pts had previously untreated, unresectable stage III NSCLC, ECOG PS 0–1 at time of study entry (and PS 0–2 at the time of randomization), ≤ 5% weight loss in preceding 3 months, FEV-1 > 1 L. Treatment consisted of P 50 mg/m2 days 1, 8, 29, 36 with E 50 mg/m2 days 1–5 and 29–33, given concurrently with chest XRT to 5,940 cGy (180 cGy/day) beginning on day 1. Non-progressive pts were randomized (4–8 weeks after completing PE/XRT) to receive D 75 mg/m2 iv every 21 days for 3 cycles vs. observation. We report an interim toxicity analysis associated to consolidation D. Results: From 3/02 to 12/05 220 have been registered and 149 pts have been randomized to consolidation D (n=73) or observation (n=76). Median age was 63.6 years (range 33–86); male/female 34.1%/65.9%; PS 0/1 at study entry 59.1%/40.9%; stage III A/B 40.6%/59.4%; 50.2% had FEV-1 > 2 (range 1–4.2); 44.3% were current smokers. Randomized pts have PS 0/1/2 44.3%/53%/2.7. Selected grade 3/4 toxicities associated to D include: neutropenia 23.3%, febrile neutropenia 8.2%, and pulmonary toxicity 9.6%. In addition, 26.7% of pts had dose modifications or delays on D arm, 45.2% had at least one grade 3/4 toxicity and 20.5% were hospitalized due to D-related toxicity, including 4 pts (5.5%) whose death was considered therapy related. Conclusions: Concurrent PE/XRT followed by consolidation D is associated with a high rate of grade 3/4 toxicities and hospitalizations, including treatment-related deaths. Updated toxicity data will be presented at the ASCO meeting. Whether consolidation D confers a survival advantage is not yet known. [Table: see text]

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