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Christine A Lydon



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    MA04 - Novel Approaches with IO (ID 900)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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      MA04.05 - Outcomes in NSCLC Patients Treated with First-Line Pembrolizumab and a PD-L1 TPS of 50-74% vs 75-100% or 50-89% vs 90-100% (ID 14358)

      14:00 - 14:05  |  Author(s): Christine A Lydon

      • Abstract
      • Presentation
      • Slides

      Background

      Among patients with NSCLC and a PD-L1 tumor proportion score (TPS) ≥50%, the response rate to the PD-1 inhibitor pembrolizumab is ~45%. Whether certain subsets of patients with a PD-L1 TPS ≥50% are more likely to benefit from treatment with a PD-1 inhibitor is currently unknown. We compared outcomes among NSCLC patients treated with first-line pembrolizumab and different PD-L1 TPS groupings: 50-74% vs 75-100% or 50-89% vs 90-100%.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively analyzed patients who received commercial pembrolizumab as first-line treatment for NSCLC with a PD-L1 TPS of ≥50% from the Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, and Massachusetts General Hospital. Clinicopathologic characteristics and clinical outcomes were compared among patients with a PD-L1 TPS of 50-74% vs 75-100% or 50-89% vs 90-100%. Event-time distributions were estimated using Kaplan-Meier and compared with the log-rank test.

      4c3880bb027f159e801041b1021e88e8 Result

      172 patients were identified for inclusion in this study. In the entire cohort, the overall response rate (ORR) to pembrolizumab was 33.9%, median progression-free survival (mPFS) was 4.8 months, and median overall survival (mOS) was 20.6 months. Compared to patients with TPS 50-74% (N=68, 39.5%), patients with TPS 75-100% (N=104, 60.5%) had a significantly higher ORR (45.2% vs 20.6%, P=0.001), a significantly longer mPFS (5.3 vs 2.5 mo, HR=0.61 [95% CI: 0.41-0.90], P=0.008), and a trend towards improved mOS (33.6 vs 20.6 mo, HR=0.60 [95% CI: 0.34-1.04], P=0.056). Compared to patients with TPS 50-89% (N=99, 57.6%), patients with TPS 90-100% (N=73, 42.4%) had a significantly higher ORR (50.7% vs 24.2%, P<0.001), a significantly longer mPFS (6.4 vs 2.8 mo, HR=0.52 [95% CI: 0.36-0.76], P<0.001), and a significantly longer mOS (33.6 vs 18.0 mo, HR=0.46 [95% CI: 0.27-0.79], P=0.008). There were no significant differences in smoking history, histology, sex, and age between patients in each TPS cutoff group.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Among NSCLCs with a PD-L1 TPS ≥50% treated with first-line pembrolizumab, higher PD-L1 TPS levels above 75% and 90% are associated with improved clinical outcomes compared to NSCLCs with lower PD-L1 levels.

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    MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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      MA25.09 - M1b Disease in the 8th Edition of IASLC Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcom (ID 11942)

      14:30 - 14:35  |  Author(s): Christine A Lydon

      • Abstract
      • Presentation
      • Slides

      Background

      The 8th edition of IASLC staging of lung cancer has revised M classification and defined M1b disease for single extrathoracic metastasis, which is distinguished from M1c with multiple extrathoracic metastases. We investigated the prevalence of M1b disease in stage IV NSCLC patients (pts), and studied the pattern of single extrathoracic metastasis and its relationship with overall survival (OS).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      567 pts with stage IV NSCLC (236 males, 331 females, median age: 63) diagnosed in 2008-2012 were reviewed to determine M stage according to the 8th edition of IASLC staging of lung cancer (M1a: separate tumor nodules in a contralateral lobe, pleural/pericardial nodule or effusion; M1b: single extrathoracic metastasis; M1c: multiple extrathoracic metastasis in one or more organs). Clinical characteristics and OS were compared according to M stage.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 567 pts, 57 pts (10%; 95%CI: 7.6-13%) had M1b disease with single extrathoracic metastasis, while 119 pts (21%) had M1a and 391 pts (69%) had M1c disease. Squamous histology was more common in M1b (9/57; 16%) than in M1a (7/119; 6%) and M1c pts (22/391; 6%) (Fisher P=0.03). The median OS of M1b pts was 14.8 months (95%CI: 12.7-24.7 months), compared to 22.7 months (95%CI: 18.5-31.6 months) for M1a and 13.4 months (95%CI: 11.8-15.3 months) for M1c pts (log-rank P < 0.0001). Among 57 M1b pts, brain was the most common site of single metastasis (n=28; 49%), followed by bone (n=16; 28%), adrenal (n=7; 12%), liver (n=3; 5%), muscle (n=2; 4%), and distant node (n=1; 2%). M1b pts with liver metastasis had shorter OS than others (median OS: 8.1 vs. 16.1 months, log-rank P=0.046). Single metastasis in M1b pts were locally treated in 31 pts (54.5%). Brain metastasis was more frequently treated with local treatment than others (26/28, 92.9%vs. 5/29, 17%; p<0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      M1b disease was noted in 10% of stage IV NSCLC pts. Squamous histology was more common in M1b than in M1a and M1c groups. Brain was the most common site of single metastasis and was often treated locally. Single liver metastasis in M1b disease was associated with shorter OS. The study characterized the unique clinical features of the new category of M1b disease among stage IV NSCLC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-35 - Tumor Volume Analysis In ALK-Rearranged NSCLC Treated with Crizotinib: Identifying an Early Marker for Clinical Outcome (ID 11720)

      16:45 - 18:00  |  Author(s): Christine A Lydon

      • Abstract

      Background

      Targeted inhibition of anaplastic lymphoma kinase (ALK) has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC) with ALK-rearrangement. We performed tumor volume analysis of ALK-rearranged advanced NSCLC treated with crizotinib to identify an early imaging marker that can predict clinical outcome.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Forty-two patients with advanced NSCLC harboring ALK-rearrangement (15 men, 27 women; median age: 55.7 years) treated with crizotinib as their first ALK-directed therapy at Dana-Farber Cancer Institute between November 2008 and June 2016. All patients had a follow-up chest CT scan at 8 +/- 3 weeks of therapy and had a dominant measurable lesion in the lung (≥1 cm) on baseline CT. Tumor volume of the dominant lung lesion was measured on baseline CT and follow-up CT at 8 +/- 3 weeks of therapy, using the previously validated technique on the volume analysis software (Vitrea ; Vital Images, Minnetonka, MN). The relationships between the 8-week volume change (%) and overall survival (OS) measured from the 8-week scan date were studied.

      4c3880bb027f159e801041b1021e88e8 Result

      The 8-week tumor volume change ranged from -99.3% to 117.5% (median: -57.7%). Using the 25 percentile of the 8-week volume change of -74%, 11 patients with >74% volume decrease at 8 weeks had a significantly longer OS compared to 31 patients with ≤74% decrease (Median OS: 92.0 months vs. 22.8 months, log-rank p=0.0048). In multivariable analyses using Cox proportional hazards models, the 8-week volume decrease of >74% remained as a significant factor associated with prolonged OS (HR=0.14, 95%CI: 0.03-0.59; Cox p=0.008) after adjusting for other significant variables including tumor stage at presentation (stage IV vs. others, HR=5.6, 95%CI: 1.29-24.3; p=0.02). Of the 31 patients with ≤74% decrease on the 8-week scan, best overall response by RECIST was partial response (PR) in 21 (68%), stable disease in 9 (29%), and progressive disease (PD) in one (3%). None of the 42 patients experienced RECIST-PD prior to the 8-week scan.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The 8-week tumor volume decrease of >74% on CT is significantly associated with longer OS in patients with ALK-rearranged NSCLC treated with crizotinib. The 8-week tumor volume analysis helps to identify patients who may benefit from alternative therapy in the early course of crizotinib therapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-02 - Early Plasma ctDNA Response Anticipates Clinical Response to First-Line Immunotherapy in Advanced NSCLC (ID 14240)

      12:00 - 13:30  |  Author(s): Christine A Lydon

      • Abstract

      Background

      Shedding of circulating tumor DNA (ctDNA) into plasma can be an independent prognostic indicator in lung cancer, and changes in plasma ctDNA levels correlate with response to targeted therapy. We hypothesized that serial assessment of plasma ctDNA by next generation sequencing (NGS) would enable early detection of response to immunotherapy in NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced NSCLC who received first-line treatment with pembrolizumab alone or in combination with platinum doublet chemotherapy at the Dana-Farber Cancer Institute were enrolled in this study. Plasma collected from patients prior to starting therapy and again at 3 and 3 weeks after starting therapy was analyzed by NGS using enhanced tagged-amplicon sequencing of hotspots and coding regions from 36 genes (InVisionSeq). The trends of the ctDNA allele frequency were correlated with radiographic responses to therapy.

      4c3880bb027f159e801041b1021e88e8 Result

      Serial plasma samples were collected on 21 patients with the following characteristics: 67% female, median age 62, 90% adenocarcinoma, 10% squamous cell carcinoma. Pembrolizumab was administered as monotherapy to 18 (86%) patients and in combination with platinum/pemetrexed in 3 (14%) patients for a median of 6 cycles. Among the 8 (38%) patients with no detectable ctDNA at baseline, 5 patients who maintained no detectable ctDNA during serial analyses responded to treatment, and 3 patients with emergence of ctDNA within the first 6 weeks of treatment initiation experienced progressive disease. In the 13 (62%) patients with detectable ctDNA at baseline, radiographic responses were preceded by earlier changes in ctDNA allele frequency. Six of 7 patients with >50% decreases in ctDNA allele fraction responded to treatment while 4 of 6 patients with progressive disease had increases in ctDNA within 6 weeks.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In advanced NSCLC treated with first-line immunotherapy, rapid decreases and clearance of ctDNA correlated with clinical benefit, while increasing or newly detectable ctDNA was a harbinger of progressive disease. These results suggest a potential role for ctDNA as an early pharmacodynamic biomarker of response or resistance to immunotherapies.

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