Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
15 Merck & Co., Inc., Kenilworth/NJ/United States of America, 16 Sidney Kimmel
Comprehensive Cancer Center at Johns Hopkins, Baltimore/MD/United States of
America
Background: Previous analyses showed no clinically significant exposureefficacy
relationship for pembrolizumab doses of 2-10 mg/kg. Population
pharmacokinetics (popPK) modeling suggested weight-based or fixed
pembrolizumab doses could maintain exposures within the established safety/
efficacy bounds. Fixed dose advantages include increased convenience, reduced
dosing error risk, and less discarded product. Pembrolizumab 200 mg Q3W
was evaluated in the KEYNOTE-024 study of pembrolizumab versus platinumdoublet
chemotherapy for treatment-naive advanced NSCLC with PD-L1 TPS
≥50% (NCT02142738). Methods: Pembrolizumab serum concentration was
quantified with an electrochemiluminescence-based immunoassay (lower limit
of quantitation, 10 ng/mL). The existing 2-compartment popPK model derived
from studies of weight-based pembrolizumab dosing was extended with
KEYNOTE-024 concentration-time data. Correlation between pembrolizumab
exposure (ie, area under the serum-concentration curve over 6 weeks [AUC ss-
]) and efficacy was assessed. Results: Median (range) weight was 69.7
6weeks
kg (38-110) in KEYNOTE-024 and 75 kg (35.7-210) in the existing popPK model
studies. In treatment-naive advanced NSCLC, there was a flat relationship
between pembrolizumab exposure and efficacy for the 200-mg fixed dose
and weight-based doses (linear regression P>0.05). Observed pembrolizumab
concentrations for 200 mg (median 1976 μg·d/mL, 90% CI 1124-3322) were
consistent with predictions (median 1751 μg·d/mL, 90% prediction interval
955-3136) and fell within the previously observed therapeutic window for 2 and
10 mg/kg (Figure). There was considerable overlap in exposures for 2 mg/kg and
200 mg, regardless of whether weight was >90 or 0 means IC
speeds up tumor growth. PPD was defined as deltaTGR>50%, corresponding
to an absolute increase in TGR greater than 50% per month. PDL1 expression
was assessed with the SP142 clone. Results: 89 pts were eligible. 58% were
male, median age 60 (41-78); 15% never smokers. 62 pts had adenocarcinoma,
21 squamous and 6 other histologies. Mutational status was unknown for
14 pts; 36% wild type, 9 pts EGFRmut, 25 pts KRASmut. PDL1 expression
was positive in 25 pts, unknown in 57 pts. 52 pts (58%) received nivolumab,
25 pembrolizumab and 12 atezolizumab. Treatement was received as 1-3rd
line in 52 pts, and as ≥ 4 th line in 37 pts. Overall, 25 pts (28%) had a response
according to RECIST 1.1 criteria, 31 (35%) a stable disease. Median OS was
14.7 months. During IC, deltaTGR was 0 in 20 pts. Among
the 20 pts with deltaTGR>0, 9 had a PPD. Characteristics (age, sex, smoking
status, pathology, number of previous line, PDL1 status) of the 9 pts were not
different from other pts. None of the PPD were pseudoprogression. Median
OS of PPD vs others was 3.2 and 23 months, respectively. PPD was not more
frequent in tumors with high baseline TGR. Conclusion: Our results suggest
that PPD is a new subset of response criteria in which IC may increase tumor
progression, leading to a poorer survival. Rapidly growing disease at study
entry nor RECIST criteria could predict the occurrence of PPD.
Keywords: Tumor growth rate, non small cell lung cancer, Immune checkpoint
inhibitors
POSTER SESSION 3 – P3.02C: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
IT –
WEDNESDAY, DECEMBER 7, 2016
Conclusion: Pembrolizumab exposure at 200 mg Q3W is similar to that of 2
mg/kg Q3W. Including data from patients with advanced NSCLC treated with
200 mg did not change the flat exposure-efficacy relationship. Along with
the superior PFS and OS provided by pembrolizumab over platinum-doublet
chemotherapy as first-line therapy for advanced NSCLC with TPS ≥50%, these
data support 200 mg Q3W as an alternative to the approved 2-mg/kg Q3W
dose.
Keywords: pembrolizumab, pharmacokinetics, dosing
POSTER SESSION 3 – P3.02C: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/
IMMUNOTHERAPY
IT –
WEDNESDAY, DECEMBER 7, 2016
P3.02C-031 IMMUNE CHECKPOINT INHIBITORS (IC) AND
PARADOXICAL PROGRESSIVE DISEASE (PPD) IN A SUBSET OF NON-
SMALL CELL LUNG CANCER (NSCLC) PATIENTS
Jihene Lahmar 1 , Laura Mezquita 1 , Serge Koscielny 2 , Francesco Facchinetti 1 ,
Maria Bluthgen 1 , Julien Adam 3 , Jordi Remon 4 , Anas Gazzah 5 , David Planchard 1 ,
Jean-Charles Soria 5 , Caroline Caramella 6 , Benjamin Besse 1
1 Department of Cancer Medicine, Gustave Roussy, Villejuif/France, 2 Department of
Biostatistics, Gustave Roussy, Villejuif/France, 3 Department of Pathology, Gustave
Roussy, Villejuif/France, 4 Department of Medical Oncology, Gustave Roussy,
Villejuif/France, 5 Department of Therapeutic Innovations and Early Trials, Gustave
Roussy, Villejuif/France, 6 Department of Radiology, Gustave Roussy, Villejuif/
France
P3.02C-032 INTERSTITIAL PNEUMONITIS ASSOCIATED WITH
IMMUNE CHECKPOINT INHIBITORS TREATMENT IN CANCER
PATIENTS
Myriam Delaunay 1 , Amelie Lusque 2 , Nicolas Meyer 3 , Jean-Marie Michot 4 ,
Judith Raimbourg 5 , Jacques Cadranel 6 , Gérard Zalcman 7 , Valerie Gounant 6 ,
Denis Moro-Sibilot 8 , Nicolas Girard 9 , Luc Thiberville 10 , David Planchard 4 , Anne
Cecile Metivier 11 , Fabrice Barlesi 12 , Eric Dansin 13 , Maurice Pérol 14 , Eric Pichon 15 ,
Oliver Gautschi 16 , Früh Martin 17 , Samia Collot 18 , Marion Jaffro 19 , Gregoire
Prevot 19 , Julie Milia-Baron 20 , Julien Mazieres 21
1 Thoracic Oncology, CHU Larrey, Toulouse/France, 2 Institut Universitaire Du Cancer
de Toulouse, Toulouse/France, 3 Dermatologist Oncology, CHU Larrey, Toulouse/
France, 4 Institut Gustave Roussy, Villejuif/France, 5 Institut de Cancerologie
de L’Ouest, Nantes/France, 6 Hôpital Tenon, Paris/France, 7 University Hospital
Bichat, Paris/France, 8 Thoracic Oncology Unit, Chest Department, Pôle Thorax
Et Vaisseaux, CHU de Grenoble, Grenoble/France, 9 Thoracic Oncology, Hospices
Civils de Lyon, Lyon/France, 10 University Hospital, Rouen/France, 11 Hopital Foch,
Suresnes/France, 12 Aix-Marseille Université, Assistance Publique Hôpitaux de
Marseille, Marseille/France, 13 Département de Cancérologie Générale, Centre
Oscar Lambret, Lille/France, 14 Groupe Thoracique Et Orl, Centre Léon Bérard,
Lyon/France, 15 CHU Tours-Bretonneau, Tours/France, 16 Medical Oncology, Lucerne
Cantonal Hospital, Luzern/Switzerland, 17 Kantonsspital St Gallen, St Gallen/
Switzerland, 18 CHU Larrey, Toulouse/France, 19 CHU Larrey Toulouse, Toulouse/
France, 20 Oncologie Thoracique, Hopital Larrey, Toulouse/France, 21 University
Hospital, Toulouse/France
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
S678 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017