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J. Cadranel
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-037 - Prognostic Impact of 1st-Line Treatment and Molecular Testing in Advanced NSCLC in France - Results of the IFCT-PREDICT.amm Study (ID 5628)
14:30 - 14:30 | Author(s): J. Cadranel
- Abstract
Background:
In 2013, recommendations for 1st line treatment in advanced NSCLC included a platinum based chemotherapy (pCT) with or without bevacizumab (BEV-pCT), an EGFR-TKI, or a non-platinum based CT (non-pCT) depending on clinical, pathological and molecular characteristics. Molecular testing for KRAS, EGFR and ALK, is routinely performed in France for advanced non-squamous NSCLC. However, the prognostic impact of the molecular status knowledge before beginning 1st line treatment is unknown.
Methods:
After a cross-validation study, KRAS, EGFR and ALK molecular status were assessed in 843 consecutive patients (pts) with previously untreated advanced NSCLC (all histologic subtypes) and categorized as: EGFR/ALK+, KRAS+, wild-type (WT), undetermined (UD) and not done (ND). Treatments from the 1st to 3rd line were separated into 4 groups: p-CT, BEVA-pCT, EGFR/ALK TKI and non-pCT. Demographic, clinical and pathological characteristics were collected and pts were followed-up until death. Overall survival (OS) and progression-free survival (PFS) for each line were determined. Prognostic factors including treatment categories (p-CT as reference) and biomarkers status (WT as reference) were studied by Cox model.
Results:
Treatments were analyzed in 767 (91.0%) of the 843 pts enrolled between 01/2013 and 02/2014. Pts were 93.1% Caucasians, 66.2% males. Median age was 62.4 yr (28-92). 13.4% were never smokers. PS ≥2 were 21.4% and 90.3% were stage IV. 76.5% had adenocarcinoma, 14.5% squamous cell carcinoma and 9% others with WT=40.4%, KRAS+=23.1%, EGFR/ALK+=10.2%, UD=5.1%, ND=21.2%. 1st line treatments were: p-CT=75.9%, BEVA-pCT=14.2%, EGFR/ALK TKI=7.8% and non-pCT=2.1%. With a 30.3 months (mo) median of follow-up, median OS and PFS were 10.7 mo and 5.3 mo, respectively. Factors independently associated with shorter OS were PS≥2 (HR=2.08, p<.0001), KRAS+, UD and ND mutation status (HR=1.40, p=.002; 1.53, p=.02; 1.29, p=.02), and non-pCT as 1st line treatment (HR=1.92, p=.01), while EGFR/ALK+ (HR=.38, p<.0001) and BEVA-pCT (HR=.54, p<.001) were associated with better survival. There was no interaction effect between biomarkers status and OS treatment groups. However, BEVA-pCT in 1st line therapy in KRAS+ and WT NSCLC (p<.0001 and <.0003, respectively) was associated with longer survival compared to p-CT, while giving a TKI or p-CT in 1st line therapy in EGFR/ALK+ NSCLC did not affect OS.
Conclusion:
Results from the IFCT-PREDICT.amm study suggest that prognosis of advanced NSCLC might be optimized in 1st line setting by the knowledge of EGFR/ALK molecular status and the opportunity to give a BEVA-pCT regimen, especially in patients with KRAS+ and WT tumor.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-032 - Interstitial Pneumonitis Associated with Immune Checkpoint Inhibitors Treatment in Cancer Patients (ID 5670)
14:30 - 14:30 | Author(s): J. Cadranel
- Abstract
Background:
Immunotherapy is now a standard of care in melanoma, lung cancer and is spreading across other tumours. Immune checkpoint inhibitors (ICI) are generally well tolerated but can also generate immune-related adverse effects. Since the first trials, pneumonitis has been identified as a rare but potentially life-threatening event.
Methods:
We conducted a retrospective study over a period of 5 months in centers experienced in ICI use in clinical trials, access programs or following national approval. We report the main features of possibly related pneumonitis occurring in patients treated with ICI with a particular focus on clinical presentation, radiologic patterns (with a double reviewing by radiologists and pulmonologists), pathology and therapeutic strategies.
Results:
We identified 71 patients with possibly related pneumonitis including 54 NSCLC and 13 melanoma. They mainly received PD1 inhibitors. Pneumonitis usually occurred in male, former or current smokers with a median age of 59 years. We observed grade 2/3 (n= 45, 65.2%) and grade 5 (n= 6, 8.7%) pneumonitis. The median duration time between the introduction of immunotherapy and the pneumonitis was 2.2 months [0.1-27.4]. Ground glass opacitiy on lung CT-scan were the most predominant lesion 80.9% (n=55), followed by consolidations 44.1% (n=30), reticulations 36.7% (n=25) and bronchiectasis in 20.6% (n=14). When performed, bronchoalveolar lavage (BAL) showed a T-lymphocytic alveolitis and transbronchial biopsy an inflammatory and lymphocytic infiltration. Pneumonitis treatment was steroids (86.6%) and/or antibiotics (67.6%). Immunotherapy was stopped after the pneumonitis for 65 cases (92.9%) and reintroduced for 12 (9.4%) cases. Twenty-four patients (34.3%) were dead at the last follow-up and 46 patients (65.7%) were still alive. Among the living patients, the pneumonitis outcome was a total recovery in 12 patients, improvement in 22 patients, stability in 10 patients, worsening evolution in 1 patient (1 unknown). Causality of immunotherapy was evaluated by investigators as “possible” for 34 patients (49.3%), “probable” for 17 (24.6%), “certain” for 15 (21.7%) other causes for 3 (4.3%) and 2 unknowns. Median overall survival from the onset of pneumonitis was 6 months.
Conclusion:
This serie, the largest to date, of immune-related pneumonitis demonstrates that it occurs usually during the first months and displays specific radiologic features. As there is no clearly identified risk factor, oncologists should be able to detect, diagnose (with CT-scan and bronchoscopy) and treat this adverse event. An early management is usually associated with a favourable outcome and requires a close collaboration between pulmonologists, radiologists and oncologists.
