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P2.37: A Case of Immune-Mediated Pneumonitis?
October 2016
Chicago/IL/UNITED STATES OF AMERICA, 4Hospital de Madrid, Norte Sanchinarro, Madrid/SPAIN, 5City of Hope Comprehensive Cancer Center, Duarte/CA/UNITED STATES OF AMERICA, 6Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw/ POLAND, 7Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville/TN/UNITED STATES OF AMERICA, 8Robert-Bosch-Krankenhaus, gerlingen/ GERMANY, 9Fondazione IRCCS Istituto Nazionale dei Tumori, Milan/ITALY, 10University of Washington, Seattle/WA/UNITED STATES OF AMERICA, 11Yale Comprehensive Cancer Center, New Haven/CT/UNITED STATES OF AMERICA, 12UT Southwestern Medical Center, Dallas/TX/UNITED STATES OF AMERICA, 13Nemocnice Na Bulovce, Prague/CZECH REPUBLIC, 14Winship Cancer Institute of Emory University, Atlanta/GA/UNITED STATES OF AMERICA, 15Roswell Park Cancer Institute, Buffalo/NJ/UNITED STATES OF AMERICA, 16Bristol-Myers Squibb, Princeton/NJ/UNITED STATES OF AMERICA, 17 Innovators BioPharma Consulting, LLC, Woodside/CA/ UNITED STATES OF AMERICA, 18Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/MD/UNITED STATES OF AMERICA, 19 Oncoclinicas do Brasil, São Paulo/BRAZIL Background: CNS mets occur in 20%e40% of pts with adv NSCLC and are associated with poor overall survival (OS; median z7 mo). We evaluated nivo in this subgroup by: 1) pooling nivo-treated pts with adv NSCLC and pretreated (pretx) stable CNS mets at baseline (BL) across CheckMate 063 (phase [ph] II), 017 (ph III), and 057 (ph III); and 2) comparing OS with nivo vs docetaxel (doc) in pts with stable BL CNS mets in CheckMate 017 and 057. Method: 1) Nivo-treated pts with adv NSCLC and pretx BL CNS mets from CheckMate 063 (n¼3), 017 (n¼9), and 057 (n¼34) were pooled to assess BL characteristics, safety, and CNS progression. 2) OS was analyzed in pts with pretx BL CNS mets and squamous (SQ; CheckMate 017) or non-SQ (NSQ; CheckMate 057) NSCLC treated with nivo 3 mg/kg Q2W vs doc 75 mg/m2 Q3W. Results: Of 46 nivo-assigned pts with pretx CNS mets, 74% had prior CNS-site radiotherapy and 85% had 2 extra-CNS sites of mets. Median follow-up was 8.4 mo (range: 0.3, 23.4); median treatment duration (n¼45; 1 pt not treated) was 2.3 mo (range: 0.03, 23.3). Any grade (gr) treatment-related (TR) adverse events (AEs) occurred in 67% of pts; gr 3e4 TRAEs occurred in 7%, with no TR deaths. CNS TRAEs occurred in 5 pts (11%) and were all gr 1e2 (paresthesia, n¼2; dizziness, somnolence, and tremor, n¼1 each). At time of overall disease progression (PD) or last tumor assessment, 33% of pts had no evidence of CNS progression (stable/ decreased CNS lesions) and 52% had unequivocal
Abstracts
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progression in the CNS (15% had no post-BL CNS assessment). In pts with pretx CNS mets from CheckMate 017, median OS (events, n; HR) with nivo (n¼9) vs doc (n¼8) was 4.99 mo vs 3.86 mo (6 vs 8; not determined); in CheckMate 057, median OS with nivo (n¼34) vs doc (n¼34) was 7.61 mo vs 7.33 mo (30 vs 27; 1.04, 95% CI: 0.62, 1.76). Conclusion: Nivo was well-tolerated in pts with adv NSCLC and pretx CNS mets, with generally low-grade toxicities. One-third of pts had no evidence of CNS progression at time of PD/last assessment. In pts with SQ and NSQ NSCLC with pretx CNS mets, median OS was similar with nivo vs doc. Additional results (including OS and CNS progression rates in pts with/without pretx CNS mets and safety/efficacy of nivo in pts with untreated BL CNS mets from CheckMate 012) will be presented. Clinical Trial Registration Numbers: NCT01721759; NCT01642004; NCT01673867 Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2016 ASCO Annual Meeting. All rights reserved.
P2.37 A Case of Immune-Mediated Pneumonitis? Track: Immunotherapy Margarida Felizardo,1 Cláudia P. Matos,1 Sofia T. Furtado,1 Encarnação Teixeira,2 José P. Coelho3 1Pulmonology, Hospital Beatriz Ângelo, Loures/PORTUGAL, 2Pulmonology, Centro Hospitalar Lisboa Norte, Lisboa/PORTUGAL, 3Medical Oncology, Hospital Beatriz Ângelo, Loures/PORTUGAL Background: Immunotherapy is an effective strategy in the treatment of advanced non-small cell lung cancer. Its associated toxicities are diverse and different from those of chemotherapy, so patients and clinicians should be alert for early signs and symptoms. Method: Review and report a case of a female patient with lung adenocarcinoma EGFR exon 20 and PDL1 expression positive that underwent 3rd line of treatment with nivolumab, with clinical and radiological deterioration and progression to ARDS after the second administration of immunotherapy. Results: CAMR, female gender, 72 years old, passive smoker. History of hypertension and osteoarticular disorder. The patient presented with a 4-month history of exertional dyspnea, dry cough, anorexia and weight
S240
loss. The thoracoabdominal CT scan showed bilateral pulmonary infiltrates with multiple confluent nodules and consolidation of the left upper lobe; bronchofibroscopy revealed generalized inflammatory signs, cytology of the bronchoalveolar lavage was positive for adenocarcinoma, CK20-, CK7 +, TTF1 +, EGFR exon 20 mutation positive. Due to osteoarticular pain a bone scan was performed and confirmed multiple bone metastasis. First line platinum-doublet chemotherapy was initiated with partial response and the patient completed 3 maintenance cycles. Disease progression was observed and she underwent a clinical trial of chemotherapy vs. immunotherapy (PDL1 expression was positive). The patient was randomized to the chemotherapy arm and completed 6 cycles with partial response. Disease progression ocurred after 7 months of follow-up and she started 3rd line of treatment with nivolumab. Onset of chest pain, nausea/vomiting, prostration and malaise after the second administration of nivolumab. Forty-eight hours after admission onset of fever, elevated inflammatory parameters and opacity of the left lung base. CT showed bilateral multiple solid nodular and ground glass lesions. Respiratory infection/immune-mediated pneumonitis/disease progression was assumed and treatment with broad spectrum antibiotics and steroids was initiated. Progressive clinical and radiological deterioration ocurred, with severe hypoxemic respiratory failure and progression to ARDS, requiring high doses of corticosteroids and invasive mechanical ventilation. The patient died 23 months after diagnosis. No autopsy was performed. Conclusion: The range of immunological toxicities is very broad and can include any organ or system. The approach of these toxicities should be multidisciplinary. Pulmonary toxicity is one of the most feared, the diagnosis should be promptly and appropriate medical treatment should be started as early as possible. Keywords: imune-mediated pneumonitis, immunotherapy, lung cancer
P2.38 Nivolumab in Clinical Practice: Real World Experience in an Argentina Oncologic Center Track: Immunotherapy Manglio M. Rizzo, Pablo Mando, Constanza Perez De La Puente, Carmen Puparelli, Federico Losco, Matías Chacón, Reinaldo Chacon,
Journal of Thoracic Oncology
Vol. 11 No. 10S
Claudio Martin Instituto Alexander Fleming, CIUDAD DE BUENOS AIRES/ARGENTINA Background: Immunotherapy has demonstrated promising results in cancer patients. Immune checkpoint inhibition with the anti- PD-1 antibody nivolumab has improved survival in metastatic lung cancer patients. The FDA approved the use of this drug in metastatic non-small cell lung cancer (NSCLC) based on an improvement in overall survival (OS) in an international, multicenter, open-label, randomized trial comparing nivolumab to docetaxel in patients with progression on or after platinum-based chemotherapy. The augmented immune response enabled by this kind of agents has led to a particular group of side effects called immune-related adverse events (irAEs). However, the toxicity profile of nivolumab was acceptable in clinical trials. We describe here the experience with nivolumab in NSCLC patients from an Oncologic Center of Argentina. Method: We included patients (pts) with NSCLC who received nivolumab in our Centre between Aug 2015 and May 2016. The adverse events were recorded from the patient chart and the responses were evaluated by the physician in charge and defined as: progressive disease (PD), stable disease (SD), partial response (PR) or complete response (CR) according to RECIST 1.1criteria. With this information, adverse events profile, clinical benefit (SD+PR) and time to progression was evaluated. All patients who received at least one dose of Nivolumab were evaluated for toxicity and efficacy. Results: 20 pts were included with a follow up of 7.13 m (r 0-17.5). 18 pts started nivolumab and 2 did not receive it due to disease progression. 61% were women, 39% current smoker, 66% were non squamous lung cancer. Median of number of chemotherapy lines before nivolumab was 2 (r 0-6), and 76% received RDT pre-nivolumab. 89% progressed to platinum treatment. Time to pre immunotherapy treatment failure was 2.84 m (IC95% 0.57-5.11). Sites of relapse or progression before nivolumab were: lung (14), lymph nodes (8), bone (3), liver (2) and adrenal gland (1). 44% were PS 0 and 50% PS 1. Number of nivolumab’s cycles was 7.5 (r 1-31). 41% presented adverse effect of any grade (g). 4 pts had hypotiroidism (g.2), 2 pyrexia, 1 diarrhea (g.1), 1 arthralgia (g.1), 1 astenia (g.2), 1 rash (g.1), 1 pneumonitis (g.3), 1 acute kidney failure (g.2). The objective response rate was evaluated in 13 pts. 8/13 (61%)had objective response (CR1/13, PR 7/13), 2/13 had SD and 3/13 PD. Time to response was 4 m (IC95% 2.36-7.46), time to progression was 6.57 m. Sites of relapse or progression were lung (7 pts), bone (3 pts), brain (1 pts), node (2 pts).
Chicago/IL/UNITED STATES OF AMERICA, 4Hospital de Madrid, Norte Sanchinarro, Madrid/SPAIN, 5City of Hope Comprehensive Cancer Center, Duarte/CA/UNITED STATES OF AMERICA, 6Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw/ POLAND, 7Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville/TN/UNITED STATES OF AMERICA, 8Robert-Bosch-Krankenhaus, gerlingen/ GERMANY, 9Fondazione IRCCS Istituto Nazionale dei Tumori, Milan/ITALY, 10University of Washington, Seattle/WA/UNITED STATES OF AMERICA, 11Yale Comprehensive Cancer Center, New Haven/CT/UNITED STATES OF AMERICA, 12UT Southwestern Medical Center, Dallas/TX/UNITED STATES OF AMERICA, 13Nemocnice Na Bulovce, Prague/CZECH REPUBLIC, 14Winship Cancer Institute of Emory University, Atlanta/GA/UNITED STATES OF AMERICA, 15Roswell Park Cancer Institute, Buffalo/NJ/UNITED STATES OF AMERICA, 16Bristol-Myers Squibb, Princeton/NJ/UNITED STATES OF AMERICA, 17 Innovators BioPharma Consulting, LLC, Woodside/CA/ UNITED STATES OF AMERICA, 18Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/MD/UNITED STATES OF AMERICA, 19 Oncoclinicas do Brasil, São Paulo/BRAZIL Background: CNS mets occur in 20%e40% of pts with adv NSCLC and are associated with poor overall survival (OS; median z7 mo). We evaluated nivo in this subgroup by: 1) pooling nivo-treated pts with adv NSCLC and pretreated (pretx) stable CNS mets at baseline (BL) across CheckMate 063 (phase [ph] II), 017 (ph III), and 057 (ph III); and 2) comparing OS with nivo vs docetaxel (doc) in pts with stable BL CNS mets in CheckMate 017 and 057. Method: 1) Nivo-treated pts with adv NSCLC and pretx BL CNS mets from CheckMate 063 (n¼3), 017 (n¼9), and 057 (n¼34) were pooled to assess BL characteristics, safety, and CNS progression. 2) OS was analyzed in pts with pretx BL CNS mets and squamous (SQ; CheckMate 017) or non-SQ (NSQ; CheckMate 057) NSCLC treated with nivo 3 mg/kg Q2W vs doc 75 mg/m2 Q3W. Results: Of 46 nivo-assigned pts with pretx CNS mets, 74% had prior CNS-site radiotherapy and 85% had 2 extra-CNS sites of mets. Median follow-up was 8.4 mo (range: 0.3, 23.4); median treatment duration (n¼45; 1 pt not treated) was 2.3 mo (range: 0.03, 23.3). Any grade (gr) treatment-related (TR) adverse events (AEs) occurred in 67% of pts; gr 3e4 TRAEs occurred in 7%, with no TR deaths. CNS TRAEs occurred in 5 pts (11%) and were all gr 1e2 (paresthesia, n¼2; dizziness, somnolence, and tremor, n¼1 each). At time of overall disease progression (PD) or last tumor assessment, 33% of pts had no evidence of CNS progression (stable/ decreased CNS lesions) and 52% had unequivocal
Abstracts
S239
progression in the CNS (15% had no post-BL CNS assessment). In pts with pretx CNS mets from CheckMate 017, median OS (events, n; HR) with nivo (n¼9) vs doc (n¼8) was 4.99 mo vs 3.86 mo (6 vs 8; not determined); in CheckMate 057, median OS with nivo (n¼34) vs doc (n¼34) was 7.61 mo vs 7.33 mo (30 vs 27; 1.04, 95% CI: 0.62, 1.76). Conclusion: Nivo was well-tolerated in pts with adv NSCLC and pretx CNS mets, with generally low-grade toxicities. One-third of pts had no evidence of CNS progression at time of PD/last assessment. In pts with SQ and NSQ NSCLC with pretx CNS mets, median OS was similar with nivo vs doc. Additional results (including OS and CNS progression rates in pts with/without pretx CNS mets and safety/efficacy of nivo in pts with untreated BL CNS mets from CheckMate 012) will be presented. Clinical Trial Registration Numbers: NCT01721759; NCT01642004; NCT01673867 Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2016 ASCO Annual Meeting. All rights reserved.
P2.37 A Case of Immune-Mediated Pneumonitis? Track: Immunotherapy Margarida Felizardo,1 Cláudia P. Matos,1 Sofia T. Furtado,1 Encarnação Teixeira,2 José P. Coelho3 1Pulmonology, Hospital Beatriz Ângelo, Loures/PORTUGAL, 2Pulmonology, Centro Hospitalar Lisboa Norte, Lisboa/PORTUGAL, 3Medical Oncology, Hospital Beatriz Ângelo, Loures/PORTUGAL Background: Immunotherapy is an effective strategy in the treatment of advanced non-small cell lung cancer. Its associated toxicities are diverse and different from those of chemotherapy, so patients and clinicians should be alert for early signs and symptoms. Method: Review and report a case of a female patient with lung adenocarcinoma EGFR exon 20 and PDL1 expression positive that underwent 3rd line of treatment with nivolumab, with clinical and radiological deterioration and progression to ARDS after the second administration of immunotherapy. Results: CAMR, female gender, 72 years old, passive smoker. History of hypertension and osteoarticular disorder. The patient presented with a 4-month history of exertional dyspnea, dry cough, anorexia and weight
S240
loss. The thoracoabdominal CT scan showed bilateral pulmonary infiltrates with multiple confluent nodules and consolidation of the left upper lobe; bronchofibroscopy revealed generalized inflammatory signs, cytology of the bronchoalveolar lavage was positive for adenocarcinoma, CK20-, CK7 +, TTF1 +, EGFR exon 20 mutation positive. Due to osteoarticular pain a bone scan was performed and confirmed multiple bone metastasis. First line platinum-doublet chemotherapy was initiated with partial response and the patient completed 3 maintenance cycles. Disease progression was observed and she underwent a clinical trial of chemotherapy vs. immunotherapy (PDL1 expression was positive). The patient was randomized to the chemotherapy arm and completed 6 cycles with partial response. Disease progression ocurred after 7 months of follow-up and she started 3rd line of treatment with nivolumab. Onset of chest pain, nausea/vomiting, prostration and malaise after the second administration of nivolumab. Forty-eight hours after admission onset of fever, elevated inflammatory parameters and opacity of the left lung base. CT showed bilateral multiple solid nodular and ground glass lesions. Respiratory infection/immune-mediated pneumonitis/disease progression was assumed and treatment with broad spectrum antibiotics and steroids was initiated. Progressive clinical and radiological deterioration ocurred, with severe hypoxemic respiratory failure and progression to ARDS, requiring high doses of corticosteroids and invasive mechanical ventilation. The patient died 23 months after diagnosis. No autopsy was performed. Conclusion: The range of immunological toxicities is very broad and can include any organ or system. The approach of these toxicities should be multidisciplinary. Pulmonary toxicity is one of the most feared, the diagnosis should be promptly and appropriate medical treatment should be started as early as possible. Keywords: imune-mediated pneumonitis, immunotherapy, lung cancer
P2.38 Nivolumab in Clinical Practice: Real World Experience in an Argentina Oncologic Center Track: Immunotherapy Manglio M. Rizzo, Pablo Mando, Constanza Perez De La Puente, Carmen Puparelli, Federico Losco, Matías Chacón, Reinaldo Chacon,
Journal of Thoracic Oncology
Vol. 11 No. 10S
Claudio Martin Instituto Alexander Fleming, CIUDAD DE BUENOS AIRES/ARGENTINA Background: Immunotherapy has demonstrated promising results in cancer patients. Immune checkpoint inhibition with the anti- PD-1 antibody nivolumab has improved survival in metastatic lung cancer patients. The FDA approved the use of this drug in metastatic non-small cell lung cancer (NSCLC) based on an improvement in overall survival (OS) in an international, multicenter, open-label, randomized trial comparing nivolumab to docetaxel in patients with progression on or after platinum-based chemotherapy. The augmented immune response enabled by this kind of agents has led to a particular group of side effects called immune-related adverse events (irAEs). However, the toxicity profile of nivolumab was acceptable in clinical trials. We describe here the experience with nivolumab in NSCLC patients from an Oncologic Center of Argentina. Method: We included patients (pts) with NSCLC who received nivolumab in our Centre between Aug 2015 and May 2016. The adverse events were recorded from the patient chart and the responses were evaluated by the physician in charge and defined as: progressive disease (PD), stable disease (SD), partial response (PR) or complete response (CR) according to RECIST 1.1criteria. With this information, adverse events profile, clinical benefit (SD+PR) and time to progression was evaluated. All patients who received at least one dose of Nivolumab were evaluated for toxicity and efficacy. Results: 20 pts were included with a follow up of 7.13 m (r 0-17.5). 18 pts started nivolumab and 2 did not receive it due to disease progression. 61% were women, 39% current smoker, 66% were non squamous lung cancer. Median of number of chemotherapy lines before nivolumab was 2 (r 0-6), and 76% received RDT pre-nivolumab. 89% progressed to platinum treatment. Time to pre immunotherapy treatment failure was 2.84 m (IC95% 0.57-5.11). Sites of relapse or progression before nivolumab were: lung (14), lymph nodes (8), bone (3), liver (2) and adrenal gland (1). 44% were PS 0 and 50% PS 1. Number of nivolumab’s cycles was 7.5 (r 1-31). 41% presented adverse effect of any grade (g). 4 pts had hypotiroidism (g.2), 2 pyrexia, 1 diarrhea (g.1), 1 arthralgia (g.1), 1 astenia (g.2), 1 rash (g.1), 1 pneumonitis (g.3), 1 acute kidney failure (g.2). The objective response rate was evaluated in 13 pts. 8/13 (61%)had objective response (CR1/13, PR 7/13), 2/13 had SD and 3/13 PD. Time to response was 4 m (IC95% 2.36-7.46), time to progression was 6.57 m. Sites of relapse or progression were lung (7 pts), bone (3 pts), brain (1 pts), node (2 pts).