Background

Major pathological response after neoadjuvant cisplatin-based chemotherapy for early-stage NSCLC has been shown to predict survival. This has not been demonstrated for neoadjuvant immune checkpoint inhibitors. In IONESCO multicenter phase II trial, 3 cycles of durvalumab were administered in stage IB>4cm–IIIA, non N2 resectable NSCLC (TNM 8^th edition) before surgery. We report here the updated analysis on disease-free survival (DFS) and overall survival (OS) and their association with residual viable tumor cells (RVT).

Methods

Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes. Specimens were reviewed for the degree of pathologic response i.e. % of RVT in the primary tumor and in any involved lymph nodes. The relationship between % of RVT as a continuous variable and outcomes (OS and DFS) was analyzed using a Cox regression model including patient characteristics (age, gender, PS, smoking status), histology, PD-L1 tumor proportion score (TPS), stage and surgical procedure.

Results

50 pts were included. 46 were eligible and received durvalumab, 43 operated, 67.4% males, median age, 61 yr; all ECOG PS 0-1; 98% (ex-)smokers; 23 adenocarcinoma, 19 squamous; clinical stages IB/IIA/IIB/IIIA = 5/13/27/1; 15 TPS ≥1%. Median % of RVT was 36.11. Median OS and DFS were not reached; 18-m OS: 89.1% [95% CI: 75.8-95.3] 18-m DFS: 73.7% [95% CI: 58.4-84.1]. In the multivariate prognostic analysis, for increasing value of % of RVT, OS and DFS were poorer (HR [95%CI]: 1.05 [1.00-1.10] p=0.04 and 1.06 [1.01-1.11] p=0.02, respectively).

Conclusions

The IFCT-1601 IONESCO trial showed for the first time that the extent of pathological response to a neoadjuvant immune checkpoint inhibitor is an independent prognostic factor of OS and DFS in NSCLC.

Clinical trial identification

NCT03030131.

Legal entity responsible for the study

French Cooperative Thoracic Intergroup (IFCT).

Funding

AstraZeneca.

Disclosure

M. Wislez: Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Roche; Non-Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Personal, Speaker’s Bureau: BMS; Non-Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Personal, Advisory Board: MSD; Non-Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Non-Financial Interests, Institutional, Principal Investigator: Lilly; Non-Financial Interests, Institutional, Principal Investigator: Merck KGaA; Non-Financial Interests, Institutional, Principal Investigator: Merus; Non-Financial Interests, Institutional, Principal Investigator: GSK; Non-Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Personal, Speaker’s Bureau: Boeringher Ingelheim. J. Mazieres: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Research Grant: Pierre Fabre. G. Zalcman: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Meeting attendance reimbursement: Pfizer; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Da Volterra; Financial Interests, Institutional, Advisory Role: Inventiva; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Da Volterra. O. Molinier: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Teaching: Menarini. V. Westeel: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Other, Travel, Accomodation, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accomodation, Expenses: BMS; Financial Interests, Personal, Other, Travel, Accomodation, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accomodation, Expenses: Roche. D. Damotte: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Board: MSD. All other authors have declared no conflicts of interest.

Background

We report the results from the advanced malignant mesothelioma (aMM) expansion cohort of the PEMBIB phase Ib trial (NCT02856425) evaluating the safety, efficacy & biomarkers of an antiangiogenic TKI (nintedanib = [N]) with an anti-PD1 immunotherapy (pembrolizumab = [P]).

Methods

Patients (Pts) with aMM that relapsed after at least one line of platinum-based combination were treated with a combination of oral [N] (150mg BID) & IV [P] (200mg Q3W) with 7 days [N] lead-in preceded [P] initiation. Baseline and on-treatment fresh tumor & blood samples were prospectively phenotyped immune cells by flow cytometry (FC). RNAseq was run on tumor samples. Immune factors were titrated by multiplex ELISA on tumor secretome and plasma.

Results

30 aMM Pts were treated and 29 evaluable for response. Median age was 68 years old (38-85) and 86% of aMM were epithelioid. The most frequent adverse events (AE) (grades 1-3) related to the combination were liver enzymes increase, fatigue, nausea and diarrhea. 4 (13.3%) Pts developed grade 3-5 immune- related AE. Patients died of cancer progression (n=14), myocarditis with thrombo-embolic event (n=1) and COVID-19 (n=1). Median follow-up was 14.8 months (95%CI [9.70-18.2]). Best Overall Response Rates (BORR) were Partial Response (PR; n=7), Stable Disease (SD; n=17) and Progressive Disease (PD; n=5). Disease Control Rate (DCR) (defined as PR + SD) was 68.4% and 46.6% at 3 and 6 months, respectively. Analyses on fresh tumor biopsies showed that all patients increased their CD3+ T-cells and circulating levels of soluble PD1 and CXCL9 under treatment. Pts developing PR had significantly higher CD45+ and CD3+ tumor infiltrative cells at baseline compared to Pts with SD & PD as BORR. Pts with DCR at 6 months had significantly higher expression of integrins on circulating effector memory CD4⁺ & CD8⁺ T cells by FC, and higher NK, T, and myeloid dendritic cells infiltrates on baseline tumor RNAseq. Pre & on-treatment IL6 and IL8 levels in tumor secretome & plasma were higher among Pts with PD.

Conclusions

With a BORR of 23% and a DCR of 47% at 6 months, [P]+[N] combination provided valuable therapeutic benefits for Pts with aMM. Flow cytometry and secretome on fresh baseline tumor biopsies are simple techniques which could be used to predict treatment efficacy in aMM Pts.

Clinical trial identification

NCT02856425.

Legal entity responsible for the study

Gustave Roussy.

Funding

Funding: Boehringer Ingelheim; Drug supply: Boehringer Ingelheim & MSD; Sponsor: Gustave Roussy.

Disclosure

C. Baldini: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Iteos; Financial Interests, Institutional, Invited Speaker: Tahio; Financial Interests, Institutional, Research Grant: BMS. N. Chaput: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Cytune Pharma. G. Zalcman: Financial Interests, Personal, Invited Speaker, outside the submitted work: BMS; Financial Interests, Personal, Invited Speaker, outside the submitted work: MSD; Financial Interests, Personal, Invited Speaker, outside the submitted work: AstraZeneca; Financial Interests, Personal, Invited Speaker, outside the submitted work: Boehringer Ingelheim; Non-Financial Interests, Personal, Advisory Board, outside the submitted work: Roche; Non-Financial Interests, Personal, Advisory Board, outside the submitted work: Takeda; Non-Financial Interests, Personal, Advisory Board, outside the submitted work: AstraZeneca; Non-Financial Interests, Personal, Advisory Board, outside the submitted work: AbbVie. C. Massard: Non-Financial Interests, Personal, Advisory Role: Amgen; Non-Financial Interests, Personal, Advisory Role: Astellas Pharma; Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: Bayer; Non-Financial Interests, Personal, Advisory Role: BeiGene; Non-Financial Interests, Personal, Advisory Role: BMS; Non-Financial Interests, Personal, Advisory Role: Celgene; Non-Financial Interests, Personal, Advisory Role: Debiopharm Group; Non-Financial Interests, Personal, Advisory Role: Genentech/Roche; Non-Financial Interests, Personal, Advisory Role: Ipsen; Non-Financial Interests, Personal, Advisory Role: Janssen; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: MSD; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Advisory Role: Pfizer; Non-Financial Interests, Personal, Advisory Role: Sanofi; Non-Financial Interests, Personal, Advisory Role: Orion; Non-Financial Interests, Personal, Advisory Role: Taiho Pharmaceuticals; Non-Financial Interests, Personal, Advisory Role: Blueprint Medicinces; Non-Financial Interests, Personal, Advisory Role: Innate Pharma; Non-Financial Interests, Personal, Advisory Role: PharmaMar; Non-Financial Interests, Personal, Advisory Role: Faron Pharmaceuticals. J-C. Soria: Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Gritstone Oncology; Financial Interests, Personal, Stocks/Shares: Relay Therapeutics; Financial Interests, Personal, Member of the Board of Directors: Hookipa Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment, sept 2017 to dec 2019: AstraZeneca. A. Marabelle: Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Servier; Non-Financial Interests, Personal, Principal Investigator: Roche/Genentech; Non-Financial Interests, Personal, Principal Investigator: BMS; Non-Financial Interests, Personal, Principal Investigator: MSD; Non-Financial Interests, Personal, Principal Investigator: Pfizer; Non-Financial Interests, Personal, Principal Investigator: Lytix Pharma; Non-Financial Interests, Personal, Principal Investigator: Eisai; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Tesaro; Non-Financial Interests, Personal, Principal Investigator: Chugai; Non-Financial Interests, Personal, Principal Investigator: Ose Immunotherapeutics; Non-Financial Interests, Personal, Principal Investigator: Sotio; Non-Financial Interests, Personal, Principal Investigator: Molecular Partners; Non-Financial Interests, Personal, Principal Investigator: IMCheck; Non-Financial Interests, Personal, Principal Investigator: Pierre Fabre; Non-Financial Interests, Personal, Principal Investigator: Adlai Nortye; Financial Interests, Personal, Stocks/Shares: Pegascy SAS; Financial Interests, Personal, Stocks/Shares: Centessa Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: HiFiBio; Financial Interests, Personal, Stocks/Shares: Shattuck Labs; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Transgene; Financial Interests, Institutional, Research Grant: Fondation MSD Avenir; Financial Interests, Institutional, Research Grant: Sanofi. All other authors have declared no conflicts of interest.

Background

Concurrent CRT (cCRT) followed by immunotherapy is the standard of care for patients (pts) with unresectable stage III NSCLC. However, nearly half of this population cannot tolerate cCRT, and thus sequential CRT (sCRT) is commonly utilized. We conducted a phase 3 trial to evaluate sugemalimab, a full-length, fully human IgG4 monoclonal antibody targeting PD-L1, as a consolidation treatment in pts with stage III NSCLC who had not progressed following cCRT or sCRT. This is the first phase 3 trial including both populations in this setting.

Methods

Eligible pts were randomized 2:1 to receive sugemalimab 1200 mg or placebo Q3W, stratified by ECOG performance status (0 vs 1), CRT type (cCRT vs sCRT), and total RT dose (<60 Gy vs ≥60 Gy). The primary endpoint was progression-free survival (PFS) by blinded independent central review according to RECIST v1.1.

Results

Of 381 pts randomized from 50 sites, 33.3% received prior sCRT, 69.6% had an ECOG performance status of 1, 69.0% had squamous cell carcinoma, and 28%/55%/16% had stage IIIA/IIIB/IIIC disease. At the pre-planned interim analysis with a median follow-up of 14 months, median PFS was 9.0 months with sugemalimab vs 5.8 months with placebo (HR 0.64; 95% CI 0.48–0.85; P=0.0026). The 12- and 18-month PFS rates were 45% vs 26% and 39% vs 23%, respectively. Consistent PFS benefit was observed regardless of whether pts received prior sCRT (median PFS 8.1 vs 4.1 months, HR 0.59) or cCRT (median PFS 10.5 vs 6.4 months, HR 0.66). Overall survival (OS) data were immature, but a trend favouring sugemalimab was observed (HR 0.44; 95% CI 0.27–0.73). The 12- and 18-month OS rates were 89% vs 76% and 82% vs 60%, respectively. Grade ≥3 treatment-emergent adverse events occurred in 24.3% of pts in the sugemalimab group and in 23.8% in the placebo group.

Conclusions

A statistically significant and clinically meaningful improvement in PFS was observed with sugemalimab vs placebo, with a well-tolerated safety profile. These results provide evidence for sugemalimab as a consolidation treatment for pts with unresectable stage IIIA–C NSCLC who have not progressed following cCRT or sCRT.

Clinical trial identification

NCT03728556.

Editorial acknowledgement

Editorial assistance was provided by Muge Qile of CStone Pharmaceuticals, and Ward A. Pedersen with Mary Lawrence of Parexel, funded by CStone Pharmaceuticals (Suzhou) Co., Ltd, Suzhou, China.

Legal entity responsible for the study

CStone Pharmaceuticals (Su Zhou) Co., Ltd.

Funding

CStone Pharmaceuticals (Suzhou) Co., Ltd, Suzhou, China.

Disclosure

N. Cui: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (Su Zhou) Co., Ltd. J. Wang: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (Su Zhou) Co., Ltd. Q. Wang: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (Su Zhou) Co., Ltd. M. Qin: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (Su Zhou) Co., Ltd. R. Zhang: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd. J. Yang: Financial Interests, Personal, Full or part-time Employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Stocks/Shares: CStone Pharmaceuticals (Su Zhou) Co., Ltd.; Financial Interests, Personal, Leadership Role: CStone Pharmaceuticals (Su Zhou) Co., Ltd. All other authors have declared no conflicts of interest.

Background

Durvalumab consolidation therapy for up to 12 months (PACIFIC regimen) is now standard of care in patients (pts) with unresectable Stage III non-small-cell lung cancer (NSCLC) without disease progression after platinum-based chemoradiotherapy (CRT). PACIFIC-R assesses the effectiveness of durvalumab in this pt population in a real-life setting.

Methods

PACIFIC-R (NCT03798535) is a large international, observational study in pts who received ≥1 dose of durvalumab (10 mg/kg Q2W) as part of an AstraZeneca-initiated expanded access program. Pts had completed platinum-based chemotherapy concurrent or sequential to radiotherapy within the previous 12 weeks without evidence of disease progression.

Results

Outcomes were assessed in the full analysis set (N=1155). Median time to durvalumab initiation after the end of RT was 52 days. Overall median durvalumab treatment duration was 337 days (11 months); 232 (20.1%) pts received treatment for >12 months (50 [4.3%] for >14 months). Pts received a median of 22 infusions. Reasons for/median time to treatment discontinuation included completion of treatment (47.6%/11.8 months; investigator decision per country protocol), disease progression (25.8%/5.1 months) and adverse event (AE; 17.5%/2.8 months). Pneumonitis was the most common AE leading to discontinuation (temporary: 5.1%; permanent: 8.7%). 214 (18.5%) pts had any-grade pneumonitis and/or interstitial lung disease (median time from durvalumab start: 74 days [2.4 months]). Of these, most events were moderate (8.8%) in severity; 2 (0.2%) and 1 (0.1%) pts had a life-threatening or fatal event, respectively. Interim analysis (51.8% of events) showed a median real-world PFS (rwPFS) of 22.5 months (95% CI, 19.7–25.5). rwPFS by baseline PD-L1 status and prior CRT will be included in the final presentation.

Conclusions

These results demonstrate the effectiveness of consolidation durvalumab after CRT in a real-world cohort of pts with unresectable Stage III NSCLC; pneumonitis events were mostly moderate in severity. Additional data from an externally sponsored study with similar enrolment criteria in Spain will be included in the final presentation.

Clinical trial identification

NCT03798535; Release date: 10 January 2019.

Editorial acknowledgement

Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Carole Mongin-Bulewski, PhD, of Ashfield MedComms (Manchester, UK), an Ashfield Health company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

N. Girard: Financial Interests, Personal, Other: AstraZeneca; Non-Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Bristol Myers Squibb; Non-Financial Interests, Personal, Other: Bristol Myers Squibb; Financial Interests, Personal, Other: Merck Sharp & Dohme; Non-Financial Interests, Personal, Other: Merck Sharp & Dohme. H.J.M. Smit: Other, Personal, Invited Speaker, Independent, paid: AstraZeneca; Other, Personal, Invited Speaker, Independent, paid: Bristol Myers Squibb; Other, Personal, Invited Speaker, Independent, paid: MSD; Other, Personal, Invited Speaker, Independent, paid: Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator, Local PI: Bayer. A. Sibille: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Other, Travel grant: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel grant: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel grant: MSD; Financial Interests, Personal, Other, Travel grant: Roche. F. McDonald: Financial Interests, Personal, Other, Honoraria and consulting fees: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Elekta; Financial Interests, Personal, Other, Consulting fees: Accuray; Financial Interests, Personal, Funding, Grant funding: MSD; Financial Interests, Personal, Other, Consulting fees: AstraZeneca. M.C.C. Garassino: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Mirati; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Institutional, Other, Honoraria: Sanofi-Aventis; Financial Interests, Personal, Advisory Role: Blueprint Medicine. A.R. Filippi: Financial Interests, Personal, Other, Scientific consultancy: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Ipsen; Financial Interests, Personal, Speaker’s Bureau: MSD. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Mirati, Novartis, PharmaMar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda. Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp & Dohme, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics. J.K. Field: Financial Interests, Personal, Other, Received Honoraria: AstraZeneca. D.C. Christoph: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Writing Engagements: AstraZeneca; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Expert Testimony: Bayer; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim; Financial Interests, Personal, Expert Testimony: Bristol Myers Squibb; Financial Interests, Personal, Expert Testimony: Chugai; Financial Interests, Personal, Expert Testimony: MSD; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Expert Testimony: Pfizer; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Expert Testimony: Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Takeda; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: MSD; Non-Financial Interests, Personal, Principal Investigator: Roche; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: DGHO; Non-Financial Interests, Personal, Member: ESMO; Non-Financial Interests, Personal, Member: IASLC. R. Fietkau: Financial Interests, Personal, Other, Grants and personal fees: AstraZeneca; Financial Interests, Personal, Other, Grants and personal fees: Merck Serono; Financial Interests, Personal, Other, Grants and personal fees: MSD; Financial Interests, Personal, Other, Grants and personal fees: Novocure; Financial Interests, Personal, Other, Personal fees: Brainlab; Financial Interests, Personal, Other, Personal fees: Bristol Myers Squibb; Financial Interests, Personal, Other, Personal fees: Fresenius Kabi. C. Chouaid: Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: AstraZeneca; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Boehringer Ingelheim; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: GlaxoSmithKline; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Roche; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Sanofi-Aventis; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Bristol Myers Squibb; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: MSD; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Lilly; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Novartis; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Pfizer; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Janssen; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Takeda; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Bayer; Financial Interests, Personal, Other, Attending Scientific Meetings, Speaking, Organizing Research, or Consulting: Amgen. S. Kao: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. W. Sawyer: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. A. Allen: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Licour: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. P. Garrido: Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: AstraZeneca; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: MSD; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Roche; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Bristol Myers Squibb; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Boehringer Ingelheim; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Pfizer; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: AbbVie; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Novartis; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Lilly; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Janssen; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Blueprint Medicines; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Takeda; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Gilead; Financial Interests, Personal, Other, Received personal fees for advisory role and/or talks: Rovi. All other authors have declared no conflicts of interest.

Background

In CASPIAN, the Phase 3 study of etoposide + cisplatin/carboplatin (EP) ± durvalumab (D) ± tremelimumab (T) as first-line treatment of ES-SCLC, D + EP demonstrated a statistically significant improvement in OS vs EP alone (data cut-off [DCO]: 11 Mar 2019; HR 0.73 [95% CI 0.59–0.91; p=0.0047]). In a subsequent analysis after a median follow-up of 25.1 mo (DCO 27 Jan 2020), OS benefit with D + EP vs EP was sustained (HR 0.75 [95% CI 0.62–0.91; nominal p=0.0032]), and D + T + EP numerically improved OS vs EP (HR 0.82 [95% CI 0.68–1.00; p=0.0451]), but did not reach statistical significance (p≤0.0418). Here we report updated OS after a median follow-up of >3 years, the longest reported to date for a phase 3 trial of EP + PD(L)1 in this disease setting.

Methods

Pts with treatment-naïve ES-SCLC were randomised 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w. Pts in the IO arms received 4 cycles of EP + D ± T, followed by maintenance D 1500 mg q4w. Pts in the EP arm received up to 6 cycles of EP. The two primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP. Serious AEs (SAEs) were assessed during long-term follow up.

Results

268, 268 and 269 pts were randomized to D + EP, D + T + EP and EP, respectively. At a DCO of 27 Mar 2021, median follow-up was 39.4 mo, 86% maturity. D + EP continued to demonstrate improved OS vs EP: HR 0.71 (95% CI 0.60–0.86; nominal p=0.0003). Median OS was 12.9 vs 10.5 mo; 22.9% vs 13.9% of pts were alive at 24 mo; and 17.6% vs 5.8% of pts were alive at 36 mo with D + EP vs EP, respectively. D + T + EP continued to numerically improve OS vs EP: HR 0.81 (95% CI 0.67–0.97; nominal p=0.02); median OS was 10.4 mo, and 15.3% of pts were alive at 36 mo. 46 pts remained on treatment with D at DCO (27 in the D + EP arm and 19 in the D + T + EP arm). In D + EP, D + T + EP and EP arms, respectively, incidences of SAEs (all cause) were 32.5%, 47.4% and 36.5%; and AEs leading to death (all cause) were 5.3%, 10.9% and 6.0%.

Conclusions

D + EP demonstrated sustained OS benefit over EP with a well-tolerated safety profile after >3 years of median follow-up, consistent with previous analyses. 3 times more pts were estimated to be alive at 3 years when treated with D + EP vs EP alone, further establishing D + EP as standard of care for first-line treatment of ES-SCLC.

Clinical trial identification

NCT03043872 (release date: February 6, 2017).

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Helen Kitchen of Ashfield MedComms (Macclesfield, UK), an Ashfield Health company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca.

Disclosure

L. Paz-Ares: Financial Interests, Personal, Leadership Role: Genomica, Altum Sequencing; Financial Interests, Personal, Other, Personal fees [travel, accommodation, other expenses]: Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol Myers Squibb, Lilly, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, Genentech, Lilly, Pfizer, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp and Dohme, AstraZeneca, Merck Serono, PharmaMar, Novartis, Celgene, Sysmex, Bayer, Amgen, Blueprint Medicines, Incyte; Financial Interests, Personal, Other, Fees (immediate family member): Novartis, Ipsen, Pfizer, Servier, Sanofi, Roche, Amgen, Merck. Y. Chen: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Writing Engagements: AstraZeneca, IPSEN; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, IPSEN, EMD Serono; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Merck, Guardant Health, Pfizer, Jazz Pharmaceuticals, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Merck, IPSEN, Jazz Pharmaceuticals. N. Reinmuth: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, MSD, Merck, Pfizer, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Hoffmann-La Roche, MSD, Merck, Pfizer, Takeda; Financial Interests, Personal and Institutional, Principal Investigator: Amgen, AstraZeneca, Beigene, BMS, Daiichi Sankyo, IO Biotech, Janssen-cilag International NV, Jiangsu Hengrui Medicine, Lilly, Merck, Merck Sharp & Dohme Corp, Novartis, Pfizer, Pharmamar, Roche, Sanofi, Takeda. K. Hotta: Financial Interests, Personal, Speaker’s Bureau: Pfizer, AstraZeneca, Chugai, Lilly, Takeda, MSD, BMS, Ono, NipponKayaku, Taiho, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Grant: MSD, AstraZeneca, Chugai, Lilly, BMS. M.J. Hochmair: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Roche, Boehringer Ingelheim, Takeda, Lilly; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, Roche, Boehringer Ingelheim, Takeda, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Roche, Boehringer Ingelheim, Takeda, Lilly. J.H. Ji: Non-Financial Interests, Personal, Invited Speaker: LG life Sciences; Non-Financial Interests, Personal, Advisory Board: HK inno.N; Non-Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Roche, Hyndai Pharm, Celltrion, Boryung Pharm. I. Bondarenko: Financial Interests, Personal and Institutional, Principal Investigator: Amgen, AstraZeneca, BMS, Lilly, Merck Sharp & Dohme Corp, Novartis, Pfizer, Roche, Sanofi, Takeda, Tesaro. H.L. Broadhurst: Financial Interests, Personal, Full or part-time Employment, Contracted to AastraZeneca: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. T. Dalvi: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H. Jiang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Genentech, Janssen, Pfizer; Non-Financial Interests, Personal and Institutional, Research Grant: AbbVie, Advaxis, Array/Pfizer, AstraZeneca, BMS, Eli Lilly, Genentech, Merck, Pfizer, Puma, Spectrum, Tesaro, Vaccinex; Non-Financial Interests, Personal and Institutional, Principal Investigator: AbbVie, Advaxis, Array/Pfizer, AstraZeneca, BMS, Eli Lilly, Genentech, Merck, Pfizer, Puma, Spectrum, Tesaro, Vaccinex. All other authors have declared no conflicts of interest.

Background

Durvalumab is the standard-of-care as consolidation therapy after chemo-radiation (ChRT) in stage III non-resecable non-small cell lung cancer (NSCLC). Its activity across NSCLC patients (pts) with genomic alterations (GA) is poorly characterized. We aimed to assess durvalumab outcomes in the context of oncogenic addition.

Methods

Retrospective study of pts with stage III non-resecable NSCLC treated with durvalumab after ChRT between Apr/15 and Oct/20 at 25 centres from Europe and United States. Clinical and biological data were collected; driver GA (dGA) included EGFR/all-BRAF/all-KRAS mutations (m) and ALK/ROS1 rearrangements (r). Radiological response was assessed according to RECIST v1.1 or investigator’s criteria. We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA.

Results

Out of 323 pts included, 43 had one dGA: KRASm (26; n=8 G12C), EGFRm (8; n=6 del19/ex21), BRAFm (5; n=4 V600E) and ALKr (4). Median age was 66 [39-84], gender ratio 1:1, with 98% PS ≤1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n=4 missing). Median PFS was 17.5 months (mo.) (95%CI, 13.2-24.9) and mOS 47 mo. (95%CI, 47-not reached [NR]). No statistically significant differences in terms of mPFS were observed between dGA vs. non-dGA pts: 14.9 mo. (95%CI, 8.1-NR) vs. 18 mo. (95%CI, 13.4-28.3) (P=1.0); mOS was immature. Median PFS and OS rate at 18 mo. by each dGA are detailed in the table. Table: 1172MO

Within dGA pts, neither OS nor PFS were correlated with PD-L1 expression, whereas PFS was positively associated with smoking status: 19.2 mo. (95%CI, 11.3-NR) vs. 5.8 mo. (95%CI, 3.9-NR) in non-smokers (P=0.001).

Conclusions

We observed limited activity of durvalumab consolidation in pts with stage III non-resecable NSCLC with dGA, except for those harbouring KRASm. Larger studies are needed to confirm these findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Auclin: Financial Interests, Institutional, Other: Mundipharma; Financial Interests, Personal and Institutional, Other: Sanofi Genzymes. R. Lopez Castro: Financial Interests, Institutional, Sponsor/Funding, Advisory role, lectures, other: Roche; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: AstraZeneca; Financial Interests, Institutional, Advisory Role, Other: Novartis. J. Bosch Barrera: Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Other: MSD; Financial Interests, Personal and Institutional, Other: BMS; Financial Interests, Personal and Institutional, Other: AstraZeneca; Financial Interests, Personal and Institutional, Other: Novartis; Financial Interests, Personal and Institutional, Other: Pierre Fabre; Financial Interests, Personal and Institutional, Other: Boehringer Ingelheim. S. Pilotto: Financial Interests, Institutional, Funding, Lectures: Roche; Financial Interests, Institutional, Funding, Lectures: Pfizer; Financial Interests, Institutional, Funding, Lectures: Merck Serono; Financial Interests, Institutional, Funding, Lectures: BMS; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Takeda. M. Tagliamento: Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Bristol Myers Squibb; Financial Interests, Institutional, Other: AstraZeneca; Financial Interests, Other: Takeda; Financial Interests, Writing Engagements: Novartis; Financial Interests, Writing Engagements: Amgen. E. Nadal: Financial Interests, Funding, Lectures: Roche; Financial Interests, Funding: Pfizer; Financial Interests, Funding, Lectures: Merck Serono; Financial Interests, Funding, Lectures: BMS; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Lilly; Financial Interests, Advisory Board: Amgen; Financial Interests, Advisory Board: Boehringer Ingelheim; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Takeda. D. Signorelli: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Other: Merck Sharp & Dohme; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Bristol Myers Squibb. B. Besse: Financial Interests, Institutional, Sponsor/Funding: AbbVie; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: BioGene; Financial Interests, Institutional, Sponsor/Funding: Blueprint Medicines; Financial Interests, Institutional, Sponsor/Funding: BMS; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Sponsor/Funding: Celgene; Financial Interests, Institutional, Sponsor/Funding: Cristal Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Institutional, Sponsor/Funding: Eli Lilly; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: Ignyta; Financial Interests, Institutional, Sponsor/Funding: Ipsen; Financial Interests, Institutional, Sponsor/Funding: Inivata; Financial Interests, Institutional, Sponsor/Funding: Janssen; Financial Interests, Institutional, Sponsor/Funding: Merck KGaA; Financial Interests, Institutional, Sponsor/Funding: MSD; Financial Interests, Institutional, Sponsor/Funding: Nektar; Financial Interests, Institutional, Sponsor/Funding: Onxeo; Financial Interests, Institutional, Sponsor/Funding: OSE Immunotherapeutics; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: PharmaMar; Financial Interests, Institutional, Sponsor/Funding: Roche-Genentech; Financial Interests, Institutional, Sponsor/Funding: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Servier; Financial Interests, Institutional, Sponsor/Funding: Spectrum Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: Takeda; Financial Interests, Institutional, Sponsor/Funding: Tiziana Pharma; Financial Interests, Institutional, Sponsor/Funding: Tolero Pharmaceuticals. D. Planchard: Financial Interests, Institutional, Advisory Role, Lectures, Clinical Research, Honoraria, other: AstraZeneca; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Celgene; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Eli Lilly; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research, Other: Merck; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research, Other: Novartis; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research, Other: Pfizer; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Other: prIME Oncology; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria: Peer CME; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research, Other: Roche; Financial Interests, Institutional, Principal Investigator: MedImmune; Financial Interests, Institutional, Principal Investigator: Sanofi-Aventis; Financial Interests, Institutional, Principal Investigator: Taiho Pharma; Financial Interests, Institutional, Principal Investigator: Novocure. L. Mezquita: Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Tecnofarma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Chugai. All other authors have declared no conflicts of interest.