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Rosalyn Anne Juergens
MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:Frank Griesinger, Lecia Sequist
- Coordinates: 9/09/2019, 14:00 - 15:30, Hilton Head (1978)
MA11.04 - Platinum Doublet + Durvalumab +/- Tremelimumab in Patients with Advanced NSCLC: A CCTG Phase IB Study - IND.226 (Now Available) (ID 927)
14:00 - 15:30 | Presenting Author(s): Rosalyn Anne Juergens
Studies of single agent immune checkpoint inhibitors with platinum-based chemotherapy in non-small cell lung cancer (NSCLC) have demonstrated survival benefit over chemotherapy alone. The primary objective of this multi-centre study was to evaluate the safety and tolerability of durvalumab (Du), a PD-L1 inhibitor, +/- tremelimumab (Tr), a CTLA-4 inhibitor, with one of four standard platinum-doublet regimens (pemetrexed (pem), gemcitabine, etoposide (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)), in order to establish a recommended phase II dose (R2PD) for each combination. This abstract updates the results in the NSCLC cohort in this study.Method
Patients (pts), regardless of tumour PD-L1 status, were enrolled into one of six dose levels (Table 1). Dose escalation was according to a Rolling Six type design. Concurrent enrollment of cohorts was allowed.Result
Seventy-three pts (median age=63 (range 34-80); 52% female; 77% non-squamous) were enrolled. The majority of drug-related adverse events (AEs) were grade 1 or 2. Most AEs were related to chemotherapy; other AEs were chemotherapy or immune-related (renal, hepatic, skin and pulmonary toxicity). AEs that were considered related to Du or Tr (immune related AEs (irAEs)) were mainly grade 1 or 2. The most common irAEs were fatigue (64%), rash/itch (42%), diarrhea/colitis (34%), anorexia (22%), thyroid dysfunction (19%), and nausea/vomiting (21/12%). The most common grade 3 or 4 irAEs were diarrhea/colitis (11%), fatigue (10%), and rash (5%). No treatment related grade 5 toxicities were reported. Twenty pts (27%) discontinued treatment due to an AE. Twelve pts (16%) discontinued treatment for toxicity related to D+/-T. Objective response rate (ORR) was 50.7% (95% CI = 38.7-62.6%). Median progression free survival (mPFS) was 6.5 months (95% CI = 5.5-9.4). Median overall survival (mOS) was 19.8 months (95% CI = 14.8-not yet reached). ORR was similar for all levels of PD-L1 staining including PD-L1 negative patients. ORR for pts with EGFR mutations (N=5) was similar to the ORR of wild type pts. Exploratory analyses suggest mPFS and mOS were longer in patients who experienced irAEs.Conclusion
In this PD-L1 unselected patient population, Du and Tr can be safely combined with full doses of platinum-doublet chemotherapy. The ORR, mPFS and mOS are similar to results reported from other immunotherapy + chemotherapy combination trials. A randomized trial, CCTG BR.34, is evaluating the incremental benefit of adding platinum doublet to Du+Tr.
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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
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
P1.01-55 - Updated Analysis of Outcomes by Histology vs Cytology PD-L1 22C3 Antibody Testing in Advanced Non-Small Cell Lung Cancer (ID 2732)
09:45 - 18:00 | Author(s): Rosalyn Anne Juergens
Immune checkpoint inhibitors (CPIs) have changed the treatment algorithm for advanced non-small cell lung cancer (NSCLC). PD-L1 expression using 22C3 immunohistochemistry (IHC) help determine the treatment options in which CPI are used. Previous studies demonstrated that PD-L1 expression is comparable on cytology versus solid biopsy/histology specimens and no difference in survival between the testing methods among PD-L1 high (≥50%) expression patients. We assess the clinical outcomes in an expanded population of patients tested for any PD-L1 status (<1%, 1 – 49%, ≥50%) using cytology versus histology specimens.Method
This retrospective cohort study reviewed both histology and cytology specimens processed for PD-L1 status between January 2015 and June 2017. All patients who had PD-L1 testing completed for advanced NSCLC and who had follow-up with a medical oncologist were included in the final analysis, regardless of PD-L1 status. Clinical characteristics were extracted from electronic medical records. Clinical outcomes were compared between cytology and histology specimens following a chart review, including overall survival (OS) (defined as time from diagnosis of advanced NSCLC to death). This was adjusted for age, ECOG, weight loss, Charlson Comorbidity Index, and receipt of palliative intent radiotherapy, targeted therapy, and CPI.Result
512 patients with PD-L1 status testing were assessed. Amongst those, 152 fulfilled eligibility criteria with cytology (n=55) and histology (n=97) samples respectively. Baseline characteristics of the two groups are comparable in age, gender, ECOG, and histological subtype. Comparatively, the cytology group had more patients who were PD-L1 high (≥50%) (60% vs 39%) and had a significantly higher number of patients with baseline pleural effusion (29% vs 12%, p=0.011) and lymph node involvement (55% vs 37%, p=0.037). The histology group received more palliative intent radiation (67% vs 36%, p=0.001) while the cytology group was more likely to receive any systemic therapy (84% vs 64%, p=0.010) and any line of CPI (31% vs 28%, p=0.048).
No difference was observed in OS between the cytology and histology groups. Median OS in the cytology group was 11.8 versus 9.8 months in the histology group (HR 0.94 (95% CI 0.676-1.321)). Amongst patients who received systemic therapy, survival was significantly longer if patients were exposed to CPI during their course of treatment regardless of cytology or histology groups. However, this finding is no longer significant among patients who receive second line treatment only (HR 0.92 (95% CI 0.54-1.58, p=0.78).
On multivariate analysis, there is a significant improvement in survival with the receipt of any systemic therapy (HR 0.20 (95% CI 0.11-0.38, p=0.000), while a baseline ECOG status of 3 compared to an ECOG status of 0 was associated with worse survival (HR 4.37, (95% CI 1.17-16.27)).Conclusion
In advanced NSCLC, specimens analyzed by cytology versus histology were equivalent in survival, suggesting that the approach to biopsy should prioritize non-invasive procedures, patient preference and disease characteristics over the specimen type. Additionally, baseline performance status and receiving treatment are associated with improved outcomes, with a trend towards harm with higher ECOG scores, signifying the importance of careful patient selection in the era of CPI.