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Roman Perez-Soler
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MA06 - Challenges in the Treatment of Early Stage NSCLC (ID 124)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Florentino Hernando-Trancho, Ayten Kayi Cangir
- Coordinates: 9/08/2019, 13:30 - 15:00, Colorado Springs (1994)
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MA06.07 - E1505: Adjuvant Chemotherapy +/- Bevacizumab for Early Stage NSCLC: Updated Chemotherapy Subset Analysis (Now Available) (ID 2885)
13:30 - 15:00 | Author(s): Roman Perez-Soler
- Abstract
- Presentation
Background
Adjuvant chemotherapy (chemo) for resected early stage NSCLC provides modest survival benefit with limited comparison data between regimens. From this trial we previously reported that adding bevacizumab (B) to adjuvant chemo failed to improve either disease free survival (DFS) or overall survival (OS). Here we update outcomes by chemotherapy regimen with an additional 30 months of follow-up.
Method
Enrolled patients with resected early stage NSCLC, stratified by stage, histology, sex, and chemo option, were randomized 1:1 to chemo alone or with B (15 mg/kg every 3 weeks for up to 1 year). Chemo consisted of a planned 4 cycles of every 3 week cisplatin with either vinorelbine (V), docetaxel (D), gemcitabine (G) or pemetrexed (P).
Result
From July 2007 to September 2013, 1501 patients were enrolled with this distribution of chemo: V 25.0%, D 22.9%, G 18.9% and P 33.2%. P was added in 2009 and restricted to non-squamous (NSq) pts. Chemo regimen was chosen (not randomized). Arms were well balanced for known prognostic factors; 28% had Sq histology. Median f/up per chemo group is: V 83.5 months(m); D 89.9m; G 87.8m; P 71.9m. In pooled analysis DFS differed by histology ranging from 29.9m(G)-43.5m(V) for NSq and 59.4m(V)-77.3m(G) for Sq. OS also differed by histology ranging from 80m(D)-98.8m(P) for NSq and 98m(G)-119m(V) for Sq. A non-significant decline in both DFS and OS was seen when B was added to D or V regimens, regardless of histology. Conversely, the addition of B to P improved both DFS (HR 0.74, p= .00994) and OS (HR 0.65, p= .00368). We thus compared outcomes across non-B regimens and though numerical differences were seen in median DFS and OS, these failed to reach statistical significance. Toxicity details were presented previously.
Conclusion
B did not improve OS when added to adjuvant chemo for patients with surgically resected early stage NSCLC, though variable DFS and OS outcomes by chemotherapy regimen have emerged with longer-term follow-up. These include a significant positive improvement in DFS and OS with B combined with P and trends of worse outcomes when B was added to other regimens. Ongoing molecular analysis of samples will hopefully elucidate the etiology of these differences.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-05 - Phase I Study of Inhaled 5-Azacytidine (5-Aza) in Patients (Pts) with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 2368)
09:45 - 18:00 | Author(s): Roman Perez-Soler
- Abstract
Background
Our previous study in an endo-bronchial NSCLC murine model suggested that aerosolized 5-Aza could inhibit cancer growth, prolong survival, and induce re-expression of methylated tumor suppressor genes. This is the first in human phase I study of 5-Aza delivered by inhalation in pts with advanced NSCLC.
Method
Main inclusion criteria: Stage IV or recurrent NSCLC with predominantly lung involvement, ≥1 prior systemic therapy, ECOG PS 0-1, and good pulmonary function. Pts were treated with inhaled 5-Aza daily, D1 to D5 and D15 to D19 of a28-day cycle. Initial dose escalation used an accelerated titration scheme, followed by a 3 + 3 dose escalation and de-escalation design. The starting dose was 15mg/m2 (derived from preclinical studies that showed it to be a safe and DNA demethylating dose), followed by 30 and 45 mg/m2. The primary objective was to determine the MTD and toxicity (especially pulmonary toxicity). Secondary objectives included PK, methylation profiles pre and post 5-Aza (bronchoscopy), efficacy (RECIST 1.1), PFS and OS.
Result
From 3/2015 to 12/2017, 8 pts were treated with 3 escalating doses of inhaled 5-Aza, including 2 at the highest level of 45mg/m2. Median follow up: 15m. Median age 70, 62.5% female, 62.5% blacks, all PS=1, 87.5% adenocarcinoma with 1 EGFR and 2 KRAS mutants, 62.5% active/former smoker, mean number of prior therapies: 3 lines. Mean treatment cycles: 3.4 (1-12). No treatment related adverse events were reported. No DLTs were observed. Preliminary PK study indicated no detectable 5-Aza in the blood. No objective response was observed, 37.5% (3/8) had stable disease (SD). Median PFS and OS were 2 m and 12 m respectively. One pt had SD > 17 m and received a total of 2 cycles, whereas another KRAS-mutant pt had SD >29 m and received a total of 12 cycles.
Conclusion
Inhaled 5-Aza was well-tolerated with no treatment-related toxicity. The administration of 5-Aza by inhalation was feasible for multiple cycles in pts with advanced NSCLC without any significant pulmonary toxicity. The methylation studies in bronchial epithelium are ongoing and will be presented. Our results suggest that inhaled 5-Aza may represent a novel and safe therapeutic strategy for patients with lung-confined malignant and/or premalignant lesions. Clinical trial information: NCT02009436. Supported by NIH CA154755
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P2.18 - Treatment of Locoregional Disease - NSCLC (ID 191)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.18-11 - Real-World Experience of Consolidation Durvalumab for Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 1895)
10:15 - 18:15 | Author(s): Roman Perez-Soler
- Abstract
Background
Durvalumab was recently approved as consolidation treatment following concurrent chemoradiation (CRT) in stage III NSCLC based on the positive PACIFIC trial demonstrating improved progression free survival (PFS) and overall survival (OS). Here, we examined the integration of durvalumab therapy after CRT in an urban comprehensive cancer care center serving a high proportion of Black and Hispanic patients. We aimed to examine treatment barriers in this diverse patient population and gain insights into real-world experience.
Method
Our study included patients treated with CRT for NSCLC (stage II-III) at Montefiore Medical Center (MMC) from 2007-2018. Retrospective analysis was conducted to evaluate patient characteristics, therapies and outcomes. Patients were grouped based on the PACIFIC trial eligibility criteria for durvalumab. PFS and OS were estimated using the Kaplan-Meier method, and comparisons between subgroups were made using log-rank testing, adjusted by Cox proportional hazards regression.
Result
146 patients completed CRT for locally advanced NSCLC from 2007 to 2018. 27% (n=40) would be considered ineligible for durvalumab based on the PACIFIC criteria (Table 1: reasons). Patient demographics were similar in ineligible vs. eligible groups: mean age 67.7 vs 67.9 years, male 57.6% vs 43.5%, Black 36.7% vs 43.5%, Hispanic 22.6% vs 30.1%. In the era of durvalumab therapy (since 9/2017), 68% (n=17) received durvalumab, including 4 patients that did not meet PACIFIC criteria due to co-morbidities and/or additional malignancy. The use of durvalumab therapy has increased with time in eligible patients from 33% in 9/2017-12/2017 to 100% in 10/2018-12/2018. The median time to initiate durvalumab following CRT has decreased from 56 days before 7/2018 to 30 days afterwards (p=0.02). Several eligible patients did not receive durvalumab due to questionable benefit in EGFR–mutant NSCLC (n=2), refusal of treatment (n=1), and unkown (n=1). Compared to patients who received durvalumab, patients who did not receive it were found to be of a lower socioeconomic status (p=0.086). Moreover, there was a trend toward improved 15-month OS rates in durvalumab-treated patients compared with patients who did not receive it (100% vs 87.5%, p=0.131).
Table 1: Reasons for ineligibility based on PACIFIC criteria for durvalumab consolidation treatment Reasons for ineligibility N (%) Severe concurrent illness 13 (32%) Additional malignancy other than NSCLC 6 (15%) Not stage III 5 (12%) Progression after chemoRT 3 (7%) Persisting Grade 3 toxicity related to chemoRT 3 (7%) Incomplete chemoRT 2 (5%) Autoimmune disease 2 (5%) Recieved alternate study 2 (5%) Lost to follow up 2 (5%) Mixed small cell histology 1 (2%) Unknown 1 (2%)
Conclusion
Our results reveal more frequent use and improved time to initiate durvalumab following CRT, as well as promising initial survival data in a real world setting. A substantial proportion of patients would be ineligible as per PACIFIC criteria, yet several received durvalumab and remain disease controlled, suggesting that further investigation of durvalumab in this population is warranted.
