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Cecile Le Pechoux
Moderator of
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MS 16 - Future Direction of Chemoradiotherapy for Inoperable Non-small Cell Lung Cancer (ID 538)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Radiotherapy
- Presentations: 5
- Moderators:Yuko Nakayama, Cecile Le Pechoux
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 502
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MS 16.01 - Is the Dose Escalation Possible? (ID 7716)
15:45 - 16:05 | Presenting Author(s): Jeffrey Bradley
- Abstract
- Presentation
Abstract not provided
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MS 16.02 - Selection of Chemotherapeutic Agents (ID 7717)
16:05 - 16:25 | Presenting Author(s): Nobuyuki Yamamoto
- Abstract
- Presentation
Abstract not provided
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MS 16.03 - Management According to the Histologic Subtypes (ID 7718)
16:25 - 16:45 | Presenting Author(s): Kazushige Hayakawa
- Abstract
- Presentation
Abstract:
The suitable characteristics of the carcinoma for definitive radiotherapy (RT) are that (a) involved areas of the disease can be covered by adequate planning target volume (PTV), and that (b) the tumor cells can be sterilized with under tolerable doses for the surrounding normal tissues. Among non-small cell lung cancer (NSCLC), squamous cell carcinoma (SQ) has the characteristics to grow locally, to spread proximally along the trachea-bronchial trees and to develop regional nodal metastases. In SQ, furthermore, surgical resection is well known to be effective even for locally advanced disease. On the other hand, non-SQ has the tendency to develop distant metastases at early T-stage. In a randomized controlled trial comparing continuous, hyperfractionated, accelerated radiotherapy (CHART) (54Gy/36fr in 12 consecutive days) with conventional RT (60Gy/30fr in 6 weeks), the SQ patients had absolute advantages of CHART in both local progression-free survival (LPFS) and overall survival (OS). Therefore, SQ is considered to be a good candidate for intensive loco-regional treatment. In RTOG 0617 trial of standard-dose versus high-dose conformal RT with concurrent and consolidation carboplatin + paclitaxel with or without cetuximab for patients with stage IIIA/B NSCLC, an EGFR H-score less than 200 (low EGFR expression) was noted more commonly in non-SQ patients whereas an EGFR H score of 200 or more (EGFR-overexpression) was more common in SQ patients (p=0.0003). In patients with an H score of 200 or higher, median OS for the cetuximab group was 42.0 months (95% CI 20.6–not reached) versus 21.2 months (17.2–29.2) for the no-cetuximab group. These results suggested that SQ patients might benefit from the addition of cetuximab to chemoradiation like SQ of the head and neck. Furthermore, on phase II study of nimotuzumab in combination with concurrent chemoradiotherapy for Japanese patients with locally advanced NSCLC, the LPFS was significantly better for SQ patients than for non-SQ patients. The results also suggested that the low in-field relapse rates might be attributed to the radio-sensitizing effect of nimotuzumab and contribute to the improved OS of SQ patients. By contrast, non-SQ patients did not benefit from nimotuzumab because the distant relapse rate was significantly higher for non-SQ than that for SQ. In non-SQ histology, EGFR mutations are well known to often appear especially in adenocarcinoma. Some clinical trials of EGFR-TKI combined with standard platinum-based chemoradiotherapy for EGFR-mutant locally advanced NSCLC are ongoing in Japan. In the future direction, the locally intensified chemoradiotherapy using high-precision RT techniques and advanced radiation sensitizers including molecular targeting drugs may be more important for SQ and newly developed systemic therapies with powers of sterilizing subclinical distant metastases may be more effective for non-SQ among locally advanced NSCLC.
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MS 16.04 - Future Direction of Immuno-Radiotherapy (ID 7719)
16:45 - 17:05 | Presenting Author(s): Wilfried Eberhardt | Author(s): T.C. Gauler, M. Stuschke
- Abstract
- Presentation
Abstract:
Introduction: Recently, systemic approaches to inperable non-small-cell lung cancer (NSCLC) in stage IV disease have been significantly improved by the introduction of a new treatment modality: immunotherapy with PD-1 antibodies. Currently, nivolumab is registered for the second-line therapy of NSCLC without prerequisite of PD-L1 expression in tumor tissue. Pembrolizumab has been registered for PD-L1 positive (> or = 1% TPS) patients in second-line and for high expressors (> or = 50% TPS) also in the first-line setting. In some countries already platinum-based combination chemotherapy (CTx) plus pembrolizumab is accepted for first-line therapy of medium expressors (1-49% TPS) and also for high expressors. Other PD-L1 antibodies have already achieved positive phase-III results (atezolizumab) or large phase-III trials have finished accrual and final results are awaited (eg. durvalumab). Based on these paradigms, the rationale for combinations with radiotherapy (RTx) in NSCLC is analyzed and trial design of currently ongoing studies as well as reported signals of first results are summarized. Material and Methods: Clinicaltrials.gov has been searched for ongoing and active clinical trials with immmunotherapy and RTx. We divided NSCLC strategies into a) locally advanced and inoperable NSCLC stage III b) advanced and inoperable stage IV NSCLC (episcopal effect) c) combinations of immunotherapy and stereotactic RTx in early disease NSCLC d) oligometastatic disease. Results: a) introduction of PD-1 antibodies into treatment strategies of inoperable stage III NSCLC will get a significant booster efffect by the recently reported outcome signals of the Pacific Trial looking at durvalumab consolidation therapy versus placebo following concurrent CTx/RTx in stage III NSCLC (press release, AZ, May 2017). PFS was signifcantly longer for the administration of durvalumab as maintenance in this situation. We expect presentation of the final results at an important Lung Cancer conference during this fall. Theroretically, intoduction by DNA double-strand breaks in patients following concurrent CTx/RTx or RTx alone could lead to an increase in tumor mutational load and could potentially enhance the efficacy of any PD-1- or PD-L1-antibody therapy. A consolidation therapy of PD-1-antibody treatment following concurrent chemoradiotherapy aiming at cure was found to be a rational strategy to improve long-term survival results in inoperable stage III NSCLC. Other trials ongoing are looking at combinations of RTx with concurrent PD-1 immunotherapy or concurrent CTx/RTx combined with concurrent adminstration of PD-1 antibody therapy.Trials outlines will be summarized and presented. Only one phase-II study including pembrolizumab has maintenenance has already been presented with ist results at ASCO 2017. Treatement was manageable and toxicity acceptable. First signals shown efficacy of this strategy but final survival data are pending. Other clincial trials are currently also looking at combinations of CTx and PD-1-immunotherapy and concurrent RTx. Also other immunotherapy drugs such as CTLA4-antibodies or combinations of both PD-1(eg. nivolumab, pembrolizumab, atezolizumab, durvalumab) and CTLA4-antibodies (ipilimumab, tremelimumab) are also being investigated in stage III NSCLC. b) few trials are also looking to enhance systemic effects of immunotherapy (PD-1/PD-L1 and CTLA-4) and concurrent RTx of tumor lesions. The so called "episcopal effect" is being investigated within several clinical studies. Theoretically, the release of tumor associated antigens (TAA) by RTx given to specific tumor lesions leading to tumor lysis including the release of antigens into the circulation could potentially enhance the systemic immunological effects of checkpoint-inhibitor therapies. Well-selected case reports have given hints to support such thesis but only randomized trials will finally verify if this approach is really valid and worthwhile. c) the stereotactic and, therefore, locally ablative RTx techniques also aiming at early inoperable NSCLC patients could also potentially benefit from combinations with new immunotherapy. Several trials are underway for combinations with nivolumab, pembrolizumab, atezolizumab and durvalumab. Finally, for all mentioned treatment strategies concurrent versus sequential administration of immunotherapy and RTx is a complete open issue. Also, permutations including combinations together with platinum-based CTx and immunotherapy together with RTx have recently become very attractive. d) Last but not least, the patient group of oligometastatic patients (M1a, M1b, M1c with less than four lesions in one organ, eg. brain) seems to be a very interesting group of patients to increase both local as well as systemic control of the treatment. Conclusions: Consolidation durvalumab may potentially become the first strategy to become a new paradigm of treatment for stage III NSCLC. We will have to wait for the final results of that trial to draw more valid conclusions for future treatment strategies. However, based on the inclusion of new immunotherapy with checkpoint inhibitors already into the standard treatment algorithms of stage IV disease in NSCLC it can be predicted that also in other disease settings these innovative approches may finally extend our potential treatment options - at least for well selected patient subsets. Referrences: Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012 Jun 28;366(26):2455-65. doi: 10.1056/NEJMoa1200694. Epub 2012 Jun 2. Rizvi NA, Mazières J, Planchard D,et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015 Mar;16(3):257-65. doi: 10.1016/S1470-2045(15)70054-9. Epub 2015 Feb 20. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. doi: 10.1056/NEJMoa1501824. Epub 2015 Apr 19. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. doi: 10.1016/S0140-6736(15)01281-7. Epub 2015 Dec 19. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. doi: 10.1016/S0140-6736(16)32517-X. Epub 2016 Dec 13. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. Hellmann MD, Rizvi NA, Goldman JW,et al. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol. 2017 Jan;18(1):31-41. doi: 10.1016/S1470-2045(16)30624-6. Epub 2016 Dec 5. Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016 Nov;17(11):1497-1508. doi: 10.1016/S1470-2045(16)30498-3. Epub 2016 Oct 10. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015 Apr 3;348(6230):124-8. doi: 10.1126/science.aaa1348. Epub 2015 Mar 12. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2017/imfinzi-significantly-reduces-the-risk-of-disease-worsening-or-death-in-the-phase-iii-pacific-trial-for-stage-iii-unresectable-lung-cancer-12052017.html
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MS 16.05 - High-Dose Boost Radiation Using SBRT/ IMRT (ID 7720)
17:05 - 17:25 | Presenting Author(s): James D. Cox
- Abstract
- Presentation
Abstract:
Chemotherapy combined with radiation therapy has become standard treatment for inoperable non-small cell lung cancer (NSCLC). The combination was first proposed in the 1970s. Although induction (neoadjuvant) chemotherapy followed by radiation therapy was initially considered preferable owing to concerns about toxicity, it eventually became clear that concurrent treatment was more effective. Similarly, low-dose radiation therapy was thought to be the safest, and radiation oncologists were loath to use any dose/fractionation regimen that exceeded standard approaches with radiation therapy alone. Chemotherapy evolved in a similar fashion. At first, single agents were used, followed by tests of various combinations of different drugs, with eventual acceptance of 2-drug combination regimens, usually consisting of a platinum compound with another agent. These regimens were combined with standard radiation therapy, usually to a dose of 60 Gy in 30 fractions using three-dimensional conformal radiation therapy (3D CRT), planned on the basis of computed tomography (CT); this combination produced tolerable adverse effect profiles that were less severe than those after the previous standard of 2D treatments based on plane radiography. The next iteration of external-beam radiation therapy was intensity-modulated radiation therapy (IMRT), which involves directing multiple beamlets at the tumor while limiting the doses to surrounding critical structures. IMRT, which depends on CT imaging for staging and treatment planning, also allowed higher fraction sizes and total doses to be tested in attempts to increase tumor control. However, use of higher total doses has had potentially intimidating results in clinical trials. In a recent prospective clinical trial of the Radiation Therapy Oncology Group (RTOG 0617) in which standard-dose 60 Gy in 30 fractions given over 6 weeks was compared with high-dose 74 Gy in 37 fractions over 7 1/2 weeks, the higher total dose actually led to poorer local control. It has been hypothesized that failure to adequately cover the gross tumor volume in the high-dose arm resulted in the higher local failure rate. For small (T1 or T2) tumors of the lung, investigators have tested very-high-dose treatments based on 3D targeting of every fraction, an approach that requires 3D imaging capability. In the United States, achieving such precise targeting has required collaborations with medical physicists in the delivery of each fraction. The next generation of radiation therapy, stereotactic body radiation therapy or SBRT, began as a treatment for lesions in the brain. In Sweden, Leksell and colleagues developed an approach that came to be known as stereotactic radiation therapy. Considered an alternative to surgical resection, stereotactic radiation therapy was predicated on immobilizing the patient with a stereotaxic frame, using multiple cobalt-60 sources in a helmet-like configuration, and administering the radiation in a single fraction. Because the goal of this approach was controlled necrosis rather than a surgical defect, this approach also came to be known as stereotactic radiosurgery. Approximately 25 years later, a similar approach was developed in which linear accelerators were used to deliver SBRT. Similar principles were used: precise imaging with of the tumor with CT and, more recently, with fluorodeoxyglucose positron emission tomography; careful and secure immobilization with various body frames; management of respiratory motion for lesions in the thorax; intensity-modulated treatment planning; and image-guided targeting. From 1 to 5 or even 10 fractions are delivered in this manner, with both the treating physician and collaborating physicist attending each treatment to ensure consistent image guidance. This approach allows the delivery of very high biological doses. SBRT has been shown to result in local control rates of 85% to 95% for tumors up to 4 cm in diameter. Proton beam therapy is the latest means to control NSCLC, particularly for tumors that are larger than the T1 or T2 tumors usually treated with SBRT. Protons differ from photons in their interactions with tissues in the body; protons are heavy particles that produce different ionization tracks and deposit most of their energy at the end of their range. Where they come to a stop is a function of their energy when they enter the body. Protons have lower energy than photons until they reach their prescribed depth, at which point they produce a peak of ionizations, the Bragg peak. This Bragg peak can be spread out to cover the tumor in depth, and the beam can be shaped in the other two dimensions by electronic or physical means to achieve a high-dose volume that has the same size and shape of the tumor. Properly directed proton therapy essentially delivers no dose beyond the gross tumor volume. The relative biologically effective dose (RBE) of proton beam therapy is approximately the same as that of x-rays, so the effects of the doses in the tumor and the surrounding normal tissues (organs at risk) are well understood. Proton beam therapy and chemotherapy interact in predictable ways, and so the toxicity patterns are similar to those with chemotherapy and photons. However, proton therapy seems to have less severe effects on blood counts. In clinical trials to date, whether with IMRT, SBRT, or protons, the greatest need seems to be to enhance the effectiveness of the systemic treatment. Considerable interest has been expressed in combining each of these radiation delivery methods with immunotherapy. The occurrence of an occasional abscopal effect with radiation therapy has given rise to cautious enthusiasm for further exploration of this area.
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Author of
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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MA 09.12 - Discussant - MA 09.08, MA 09.09, MA 09.10, MA 09.11 (ID 10843)
12:15 - 12:30 | Presenting Author(s): Cecile Le Pechoux
- Abstract
- Presentation
Abstract not provided
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P1.08 - Locally Advanced NSCLC (ID 694)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.08-009 - Neutrophilia as Prognostic Biomarker in Locally Advanced Stage III Lung Cancer (ID 8920)
09:30 - 09:30 | Author(s): Cecile Le Pechoux
- Abstract
Background:
To study the prognostic value of leucocyte disorders in two retrospective cohorts of stage III Non-Small Cell Lung Cancer (NSCLC) patients, and to compare their accuracy with established prognostic markers.
Method:
Clinical records of consecutive previously untreated NSCLC patients in our Institution between June 2001 and September 2016 for stage III NSCLC were collected. The prognostic value of pretreatment leucocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophil count exceeding 10 and 7 G/L, respectively.
Result:
We identified 238 patients (145 patients prospectively registered through MSN study (NCT02105168) with 136 additional patients), displaying baseline leukocytosis or neutrophilia in 39% and 40% respectively. Most were diagnosed with adenocarcinoma (48%), and stage IIIB NSCLC (58%). 3-year actuarial overall survival (OS) and progression-free survival (PFS) were 35% and 27% respectively. Local relapses were reported in 100 patients (42%), and distant metastases in 132 patients (55%). In multivariate analysis, leukocytosis, neutrophilia, and induction chemotherapy regimen based on carboplatin/paclitaxel were associated with worse OS and PFS (p<0.05). Neutrophilia independently decreased Locoregional Control (LRC) (HR=2.5, p<0.001) and Distant Metastasis Control (DMC) (HR=2.1, p<0.001). Neutrophilia was significantly associated with worse brain metastasis control (p=0.004), mostly in adenocarcinoma patients (p<0.001). Figure 1
Conclusion:
In stage III NSCLC patients, treated with concurrent cisplatin-based chemoradiation, baseline leukocytosis and neutrophilia predict OS, PFS, LRC, and DMC. In addition with previously available markers, this independent cost-effective biomarker could help to stratify stage III NSCLC population with more accuracy.
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-038 - Determinants of Frailty and Treatment Toxicity in Non-Small Cell Lung Cancer Patient (ID 9566)
09:00 - 09:00 | Author(s): Cecile Le Pechoux
- Abstract
Background:
Platinum-based chemotherapy remains a first line treatment for advanced non-small-cell lung cancers (NSCLC). Despite better individualization of treatment, some patients will seek frequent medical attention because of cancer-related complications or treatment toxicity. This can negatively impact patient’s quality of life and health care resources. This study aimed to identify biological and clinical factors predictive of frailty and treatment toxicity among NSCLC patients eligible for first-line platinum-based chemotherapy.
Method:
Using our institutional medical charts, we retrospectively extracted data on stage III and IV NSCLC patients diagnosed between December 2011 and November 2015 who had received a first-line platinum based chemotherapy. The primary outcome is defined as any unplanned emergency visit and/or unplanned hospitalization for cancer or treatment related complications. Using multivariate logistic regression model with step by step method, we defined baseline biological and clinical determinants associated with the primary outcome.
Result:Table 1. First Multivariate Analysis
We included 227 patients. Mean age was 60 years old, 65% were male, 46% current smokers, 10% PS 2-3 and 74% had adenocarcinoma histology. 20,7% patients had locally advanced disease (Stage III) treated by chemoradiation and 78,4% had metastatic disease treated by exclusive chemotherapy. Median overall survival (OS) was 15 months and PFS 6 months. Overall, 55 % (122/227) met the primary outcome. There were 14 variables (Table 1) included in the first multivariate analysis before computer based step by step approach. In the final model (not shown), albumin level <35 g/L (OR 2.24 95% IC 1.14- 4.38, p= 0.02) was an independent predictor of the primary outcome. There was also a trend for squamous cell carcinoma subtype (OR 2.27 95% IC 0.872- 5.914, p= 0.09).Variable OR 95% CI Age ≥ 62 Years-old 1.61 0.70 - 3.68 Adenocarcinoma - Squamous Cell Carcinoma - NSCLC other 1 2.43 0.50 0.61- 9.61 1.45 – 1.74 Performance scale ≥ 1 1.35 0.57 – 3.18 Number of metastasis ≥ 2 1.36 0.58 – 3.18 Pleural metastasis 2.04 0.53 – 7.86 Weight loss ≥10% or ≥3 kg 1.00 0.41 – 2.43 ≥ 3 prescription drugs per day 0.98 0.42 – 2.28 Current smoker - Former Smoker - Never smoker 1 0.56 1.10 0.24 – 1.30 0.24 – 5.11 Neutrophils count ≥ 7500/ mm[3] 1.57 0.70 – 3.54 Lymphocytes count ≤ 1000/ mm[3] 1.04 0.34 – 3.22 Albumin ≤ 35 g/L 2.70 0.93 – 7.69 LDH ≥ 247 U/L 0.93 0.37 – 2.30
Conclusion:
Low albumin level is a determinant of frailty in patients eligible for platinum-based chemotherapy. Early intervention in these subgroups could benefit patient’s quality of life and health care expenses. (Medicoeconomic analysis will be presented).
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-005 - Impact of Baseline Leptomeningeal and Brain Metastases on Immunotherapy Outcomes in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 7958)
09:30 - 09:30 | Author(s): Cecile Le Pechoux
- Abstract
Background:
Central nervous system (CNS) involvement is frequent in NSCLC patients and associated with poor prognosis. However, its impact on immune checkpoints inhibitors’ (ICI) outcomes remains unknown.
Method:
We retrospectively collected the clinical and imaging data of a cohort of 271 patients treated with ICI in our institute from Nov. 2012 to April 2017. We analyzed overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR), and CNS outcomes using brain CT scan and/or MRI. Both body and CNS outcomes were assessed prospectively by investigators.
Result:
With a median follow up of 17 months (95% IC 15-21), 259 patients were evaluated, 48 (19%) had CNS involvement before immunotherapy; 225 were (87%) smokers, 78% had PS ≤1, with median age of 63.1; 166 (64%) had adenocarcinoma; 67 (26%) were KRASmut, 14 (5%) EGFRmut and 3 (1%) ALK positive. PDL1 was ≥1% by immunohistochemistry in 68 (28%), negative in 28 (11%) and unknown in 163 patients. Median number of prior lines was 1 (0-11). The global ORR was 20%. The median OS was 8 months (95% IC 6-11). No difference was observed in OS between CNS+ vs. CNS- population (p= 0.09). The global ORR was 18% vs. 20%, in CNS+ and CNS- patients, respectively (p=1). To date, CNS–relative data are available for 36 patients: n= 32 brain metastasis, n=7 meningeal carcinomatosis, including 4 cytological positivity, n=2 leptomeningeal and n=1 medullar metastasis. Thirty-one patients (86%) had brain target lesions and 15 were evaluable for CNS outcome (CNS progressive disease (PD) before starting ICI and/or no brain radiation therapy (RT) in the previous 6 months. Median interval between consecutive CNS assessments was 2 months. Twenty-two had CNS PD before immunotherapy: 41% (9/22) received radiation therapy (RT) the month before immunotherapy (4 whole brain RT, 5 stereotactic). No differences were observed according to prior RT, with a median OS of 10 months (95%IC 2-NR) vs. 8 months. (95%IC 5-NR) for prior vs. no prior RT (p=0.79). The median OS for the 7 patients with meningeal carcinomatosis was 2 months (0 to 20). The CNS ORR was 27% (4/15, 3 partial, 1 complete response) and CNS DCR was 60% (9/15). One CNS pseudo progression (7%) and one dissociated brain response (7%) were observed.
Conclusion:
CNS involvement did not seem to be associated with a negative impact on immunotherapy outcomes in advanced NSCLC patients. Final analysis of the entire cohort will be presented.
