Real-world use of systemic therapy in elderly patients with malignant pleural mesothelioma (MPM)

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Annals of Oncology

Real-world use of systemic therapy in elderly patients with malignant pleural mesothelioma (MPM)

S. Cedres1, J.D. Assaf2, P. Iranzo1, A. Callejo1, N. Pardo1, A. Navarro1, A. Martinez-Marti1, G. Rodriguez1, V. Monton1, J. Gonzalo3, J.M. Miquel3, A. Pedrola3, R. Dienstmann4, E. Felip5 1 Medical Oncology, Vall d’Hebron Institute of Oncology and University Hospital, Barcelona, Spain, 2Oncology, Vall d’Hebron University Hospital, Barcelona, Spain, 3 Medical Oncology, Vall d’Hebron Institute of Oncology, Barcelona, Spain, 4Oncology Data Science, Vall d’Hebron University Hospital, Barcelona, Spain, 5Medical Oncology Service (Lung Cancer Unit), Vall d’Hebron University Hospital, Barcelona, Spain

Advisory / Consultancy: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: Apmhera; Advisory / Consultancy: Lilly; Honoraria (institution): Merck. P. Iranzo: Advisory / Consultancy: Roche; Advisory / Consultancy: Grunenthal; Advisory / Consultancy, Travel / Accommodation / Expenses: Kyowa Kirin; Advisory / Consultancy: Rovi; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. A. Callejo: Advisory / Consultancy: Roche ; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb. N. Pardo: Advisory / Consultancy, Travel / Accommodation / Expenses: roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Bristol Myers Squibb. A. Navarro: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb ; Speaker Bureau / Expert testimony: Orizon Genomics. A. Martinez-Marti: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche ; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim ; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharp. R. Dienstmann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony: Symphogen; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (institution): Merck. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: Abbvie; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Blue Print Medicines; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: guardant health ; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck KgaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck, Sharp and Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: Janssen. All other authors have declared no conflicts of interest.

v752 | Thoracic Malignancies, Other

Pemetrexed/cisplatin versus gemcitabine/cisplatin as first-line treatment for Egyptian patients with malignant pleural mesothelioma

M.O. Alorabi1, H.M. El Wakil1, M.M. El-Mahdy2, D.A. Salem1, A.E. Essa1, A.M. Gaballah1 Clinical Oncology, Ain Shams Faculty of Medicine, Cairo, Egypt, 2Pathology, Ain Shams Faculty of Medicine, Cairo, Egypt

1

Background: The combination of cisplatin and pemetrexed is considered the standard of care front line regimen for malignant pleural mesothelioma (MPM). Several phase II trials demonstrated comparable response and survival rates with the use of gemcitabine and cisplatin. Few retrospective studies have compared the two regimens and with conflicting results. However, no prospective clinical trial has compared them directly. Methods: Between June 2015 and September 2017, 51 chemotherapy-naı¨ve MPM Pts were randomized 1:1 to receive either pemetrexed (500 mg/m2) and cisplatin (75mg/m2) (PC) or gemcitabine 1000 mg/m2 on days 1 and 8 combined with cisplatin (75 mg/m2) on day 1 (GC). Chemotherapy was repeated every 3 weeks for a maximum of six cycles unless there was earlier evidence of disease progression or unacceptable toxicity. We used modified RECIST criteria for mesothelioma to evaluate treatment response and CTCAE v4.0 to assess toxicity. Results: The mean age was 52.5 years with males representing 51% of Pts. The ECOG PS was 0, I, and II in 3.9, 86.3, and 9.8% of cases, respectively. Epithelial histology was the most common (88.2%) followed by biphasic (9.8%) and sarcomatoid (2%). 6 pts had stage II disease, whereas 45 had stage III or IV. The baseline characteristics of the PC arm (N ¼ 26) and GC arm (N ¼ 25) were well-balanced in the age, gender, ECOG, pathology, and stage. RR with PC was 53.8% compared with 36% for GC (p value ¼ 0.132). Significant superiorities in PFS and OS were observed with PC therapy. For the PC pts, the median PFS was 10.45 vs. 8.4 months for the GC Pts (log-rank p-Value < 0.001, HR ¼ 3.23, CI (95%) ¼ 1.693  6.175). The median OS was 16.15 months for the PC arm and 13.1 months for the GC arm (log-rank p-Value ¼ 0.020, HR ¼ 1.91, CI (95%) ¼ 1.042  3.496). In general, hematological toxicities were more frequent in both arms in comparison to other types of toxicities. Neutropenia tended to be more severe with GC, whereas nausea was more frequent with PC. However, these differences in toxicity were statistically insignificant. Conclusions: First-line treatment of MPM with PC resulted in statistically significant improvement in PFS and OS compared to GC, therefore it should remain the standard of care for this group of pts. Legal entity responsible for the study: Ain Shams Faculty of Medicine IRB. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

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Accuracy of pathologic evaluation for thymic epithelial tumors in an Italian reference centre

G. Galli1, A. Fabbri2, R. Ferrara1, A. Prelaj1, C. Proto1, D. Signorelli1, A. De Toma1, F. Pagani1, N. Zilembo1, M. Ganzinelli1, G. Pruneri2, F.G.M. de Braud1, M.C. Garassino1, G. Lo Russo1 1 Medical Oncology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 2Diagnostic Pathology and Laboratory, Istituto Nazionale dei Tumori di Milano Fondazione IRCCS, Milan, Italy Background: Thymic Epithelial Tumors (TETs) are rare entities, which can be diagnostic challenges for Pathologists. It has been proven that patients’ referral to a Center with an expert Pathologist is a key factor in obtaining the correct diagnosis. As therapeutic options vary widely for the different entities of TET spectrum, an accurate diagnosis is essential in the therapeutic planning. We aimed at investigating this topic, analyzing pathologic second opinions in a single reference Centre. Methods: We retrospectively reviewed all the cases which obtained a pathologic second opinion, after being diagnosed elsewhere with a TET or for a suspicion of TET, at the Istituto Nazionale dei Tumori (INT), Milan, Italy, between 2010 and 2019. Descriptive statistics were used for qualitative variables. Concordance between diagnoses was estimated through Cohen’s k. Results: We identified 278 cases; 72 of them received a pathologic revision in INT. Among these cases, initial diagnosis was thymoma A in 5 cases, thymoma AB in 3 cases, thymoma B1 in 5 cases, thymoma B2 in 15 cases, thymoma B3 in 7 cases, thymoma Not Otherwise Specified (NOS) in 8 cases, thymic carcinoma in 17 cases, carcinoma NOS in 8 cases, carcinoma with different histology in 3 cases, lymphoblastic lymphoma in one case. INT pathologic revision changed the diagnosis in 41 (56.9%) cases, with a potential shift in therapeutic approach in 32 (44.4%). In particular, 12 cases of carcinoma NOS or lymphoma were reviewed as thymic carcinoma (10 cases) or thymoma (2 cases); 9 cases of thymic carcinoma were reviewed as cases of thymoma (7 B3, 2 B2); 11 cases of thymoma were reviewed as different thymoma subtypes (9 cases), or thymic carcinoma (one case), or diffuse large B cell lymphoma (one case). Concordance between Pathologists was moderate when the initial diagnosis was thymoma (74.7%, k 0.447), only slight when the initial diagnosis was thymic carcinoma (60.5%, k 0.139). Conclusions: A change in histological characterization was documented in a significant percentage of cases initially diagnosed in other Centers, not rarely with potential therapeutic implications. Therefore, in the approach to TETs as well as for other rare diseases, patients’ referral to a reference Centre with high pathology expertise is strongly recommended.

Volume 30 | Supplement 5 | October 2019

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Background: MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. The incidence of MPM in elderly is increasing and these patients (p) require special consideration due to multiple comorbidities and increased risk of toxicities. The objective of this study is to characterize elderly p diagnosed with MPM at our institution and evaluate overall survival in this population. Methods: One hundred forty-seven MPM p diagnosed at Vall dHebron Institute of Oncology between November 2002 and December 2016 were reviewed. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: Patient’s characteristics: median age 68 years (y) (51-86 years), males: 70%, performance status (PS)1: 67%, asbestos exposure: 72%, epithelioid subtype: 73%. First line chemotherapy was offered to 83% of p (73% cisplatin-pemetrexed and 21% carboplatin-pemetrexed). Median progression free survival (PFS) first line was 4.9 months (m;CI95% 3.6-5.6). Clinical trial was offered as second-line regimen in 34%. Median survival (OS) in overall population was 16.8 m (95%CI13.2-22.2) and in those treated with chemotherapy was 20.6 m (95%17.1-23.6). Epitheliod histology, PS 0, neutrophil-lymphocyte ratio >5 and treatment with cisplatin vs carboplatin were associated with significant improvements in OS. In total, 59 p were >70y, 42 p > 75y and 19 p > 80y. Elderly p (>70y) received first line in 66% of cases, with carboplatin-pemetrexed in 76%. Median PFS in first line was 4.8 m (95%CI 3.7-4.7m). No differences in treatment discontinuation by toxicity neither dose reductions were found (6% vs 4% and 6 vs 7% in elderly vs < 70y, respectively). Second line was given in 42% of elderly. Median OS in elderly p receiving chemotherapy was 15.1 m vs 2.7 m with best supportive care (p < 0.001). Epithelioid histology, PS 0 and eligibility to first line chemotherapy were significant prognostic factors in elderly p (p < 0.001). Conclusions: In our real world experience, chemotherapy was feasible in most elderly p with MPM and does not associates with inferior outcomes or higher toxicity compared to younger population. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: S. Cedres: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche;

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