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Anne-Marie C. Dingemans
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Lunch & Poster Display session (ID 58)
- Event: ELCC 2019
- Type: Poster Display session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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22P - Paclitaxel/ carboplatin/ bevacizumab in non-small cell lung cancer patients induces peripheral effector CD8 T cell proliferation that could be prone for treatment with checkpoint inhibitors (ID 384)
12:30 - 13:00 | Author(s): Anne-Marie C. Dingemans
- Abstract
Background
Checkpoint inhibitors targeting programmed death receptor (PD)-1 or PD-ligand 1 (PD-L1) became the cornerstone in the treatment of advanced NSCLC. Several phase III trials showed a better overall survival by treating with combination chemotherapy and checkpoint inhibition, suggesting that addition of chemotherapy increased the response to checkpoint inhibitors. Recently, peripheral blood biomarkers such as Ki67+PD-1+CD8 cells were found to be predictive for clinical outcome with PD-1 treatment. Knowing more about immune modulatory capacities of chemotherapy can help us to design better treatment strategies. We investigated the immune-modulatory effects of paclitaxel/carboplatin/bevacizumab (PCB), focusing on known immune populations associated with response to checkpoint inhibitors in peripheral blood.
a9ded1e5ce5d75814730bb4caaf49419 Methods
In the NVALT 12 study, 223 patients with advanced NSCLC were enrolled to receive PCB, with or without nitroglycerin patch. At baseline and after the first and second treatment cycle, peripheral blood was drawn. By flow cytometry, the proportions of T cells and several subsets and co-inhibitory receptors of these, B cells and monocytes were determined.
20c51b5f4e9aeb5334c90ff072e6f928 Results
6 weeks after starting treatment with PCB, the proportions of T cells were significantly increased compared to baseline values. Within the T cells subsets, proliferation of CD4 T cells remained stable whereas proliferation of CD8 T cells (Ki67+) were significantly increased. The proliferating Ki67+ CD8 T cells expresses more PD-1 compared to non-proliferating CD8 T cells. However, patients with >2 fold increased proliferation of T cells did not show a better outcome.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Paclitaxel/ carboplatin/ bevacizumab induces proliferation of CD8 T cells which expresses more co-inhibitory checkpoint molecules. Progression free and overall survival was unchanged by this increase on its own, showing the rationale to combine PCB with checkpoint inhibition in lung cancer, as used in Impower 150.
b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
NCT01171170.
7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
NVALT.
682889d0a1d3b50267a69346a750433d Disclosure
D. Dumoulin: Speakers fee: BMS, Roche, Pfizer, Novartis. A-M.C. Dingemans: Advisory boards, lectures: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Pfizer, BMS, Amgen, Novartis, MSD, Takeda (honoraria to institution). J.G. Aerts: Advisory boards: BMS, Boehringer Ingelheim, MSD, AstraZeneca, Eli Lilly, Takeda, Amphera; Stock owner: Amphera B.V. All other authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25
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Mini Oral session III (ID 65)
- Event: ELCC 2019
- Type: Mini Oral session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/12/2019, 17:45 - 18:45, Room C
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86O - The effect of prophylactic cranial irradiation (PCI) for young stage III NSCLC patients: Subgroup analyses of the NVALT-11/DLCRG-02 study (ID 524)
17:45 - 18:45 | Author(s): Anne-Marie C. Dingemans
- Abstract
- Presentation
Background
The NVALT-11/DLCRG-02 phase III study compared PCI to observation after chemo-radiotherapy (RT) for stage III NSCLC and showed a significant decrease in the cumulative incidence of symptomatic brain metastases (BM) in the PCI arm at two years (7% vs 27% [HR 0.23]). We here performed exploratory subgroup analyses.
a9ded1e5ce5d75814730bb4caaf49419 Methods
Two year cumulative incidence rates were calculated and competing risk regression, with death of any cause as competing risk, was used to examine the time to symptomatic BM in the following subgroups: age, gender, performance status, disease stage and tumour type, prior surgery, chemotherapy cycles, thoracic RT dose and total concurrent chemo-RT treatment time. For continuous variables, the median was used as a cut-off value. The effect of PCI was only examined if the initial result was significant.
20c51b5f4e9aeb5334c90ff072e6f928 Results
In total, 174 patients were analysed. The symptomatic BM incidence was significantly lower in the subgroup of older (>61 years) versus younger ( = <61 years) patients (7% vs 26% [HR 0.25]). Stratified by age, PCI only significantly reduced the symptomatic BM incidence in younger patients (9% vs 42% [HR 0.18])(Table).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
The symptomatic BM incidence was significantly lower in older (>61 years) compared to younger ( = <61 years) patients, likely due to higher numbers of adenocarcinoma in the younger patients group. The effect of PCI was only significant in younger patients. This study was randomized based on treatment allocation and subgroups might be too small to detect significant differences. Therefore, our results are hypothesis generating and should be prospectively tested.
b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
NCT01282437.
7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study
Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT).
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25Only 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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Oligometastatic and oligoprogressive disease: A new era? (ID 39)
- Event: ELCC 2019
- Type: Educational session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/12/2019, 14:30 - 16:00, Room A
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How to define it? How to treat it? (ID 98)
14:30 - 16:00 | Presenting Author(s): Anne-Marie C. Dingemans
- Abstract
- Presentation
Abstract not provided
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Proffered Paper session I (ID 57)
- Event: ELCC 2019
- Type: Proffered Paper session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/10/2019, 16:30 - 18:15, Room C
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Invited Discussant 68O and 69O (ID 666)
16:30 - 18:15 | Presenting Author(s): Anne-Marie C. Dingemans
- Abstract
- Presentation
Abstract not provided
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