Certified Lung Cancer Centers Research Articles

Personalized Treatment for Patients With Lung Cancer.

Lung cancer is the most common cause of death among all types of cancer in Germany, with an annual death rate of 45 000 patients. Over the past 15 years, innovations in diagnosis and treatment have prolonged the survival of patients with non-small-cell lung cancer in all tumor stages. This review of the diagnosis and treatment of lung cancer is based on current national and international guidelines, and on prospective trials with the highest possible level of evidence that were retrieved by a selective search of the literature. Improved outcomes in patients with non-small-cell lung cancer (85% of new diagnoses) were achieved with the aid of precise diagnostic techniques, including functional imaging and endobronchial procedures for localized disease stage. Contemporary surgical and radio-oncological technologies reduce the morbidity and expand the boundaries of local therapy. Molecular pathology, including the assessment of predictive biomarkers, is an integral part of the diagnostic evaluation of non-small-cell lung cancer in all tumor stages; it enables stratified cytotoxic/molecularly targeted treatments and immunotherapies and improves patient-reported outcomes. The percentage of long-term survivors in the metastatic stage has doubled by the introduction of immunotherapy. In contrast, there has been no major improvement in the survival of patients with small-cell lung cancer (15% of new diagnoses). In addition to the implementation of lung cancer screening in high-risk populations, the further development and consistent implementation of personalized diagnosis and treatment in certified lung cancer centers can be expected to prolong survival and improve the patients' quality of life.

Personalized Treatment for Patients With Lung Cancer.

Lung cancer is the most common cause of death among all types of cancer in Germany, with an annual death rate of 45 000 patients. Over the past 15 years, innovations in diagnosis and treatment have prolonged the survival of patients with non-small-cell lung cancer in all tumor stages. This review of the diagnosis and treatment of lung cancer is based on current national and international guidelines, and on prospective trials with the highest possible level of evidence that were retrieved by a selective search of the literature. Improved outcomes in patients with non-small-cell lung cancer (85% of new diagnoses) were achieved with the aid of precise diagnostic techniques, including functional imaging and endobronchial procedures for localized disease stage. Contemporary surgical and radio-oncological technologies reduce the morbidity and expand the boundaries of local therapy. Molecular pathology, including the assessment of predictive biomarkers, is an integral part of the diagnostic evaluation of non-small-cell lung cancer in all tumor stages; it enables stratified cytotoxic/molecularly targeted treatments and immunotherapies and improves patient-reported outcomes. The percentage of long-term survivors in the metastatic stage has doubled by the introduction of immunotherapy. In contrast, there has been no major improvement in the survival of patients with small-cell lung cancer (15% of new diagnoses). In addition to the implementation of lung cancer screening in high-risk populations, the further development and consistent implementation of personalized diagnosis and treatment in certified lung cancer centers can be expected to prolong survival and improve the patients' quality of life.

Heidelberg Milestones Communication (HeiMeKOM) - Experiences, Best Practice Examples and Recommendations from the Final Symposium on January 30 and 31 in 2020

The National Cancer Plan emphasises the importance of medical communication and calls for its integration into medical education and training. In this context, the Milestone Communication Approach meets the communicative challenges in dealing with lung cancer patients. Interprofessional tandems, consisting of doctors and nurses, conduct structured conversations at defined moments with patients and their relatives. The concept aims at shared decision making, continuity in the care of lung cancer patients and the early integration of palliative care. During the symposium on the Heidelberg Milestone Communication in January 2020, recommendations on the care situation of lung cancer patients in advanced stages were developed. In addition, the further adaptability of HeiMeKOM to other settings and hospitals and to other diseases was discussed as well as the possibility of implementing such a concept in standard care. This article presents the experiences, best practice examples and recommendations discussed during the symposium in order to enable their extrapolation to other similarly oriented projects. The long-term goal is to transfer the milestone concept to other hospital, primarily certified lung cancer centers, and to ensure permanent funding. For further dissemination of the concept and, above all, to have it established in standard care, health policy awareness and support are required in addition to the integration of the concept in competence catalogues of continuing medical and nursing education.

139P The impact of TP53 mutations on EGFR mt+ NSCLC IV patients treated with 3rd generation TKI on 2nd line or further line therapy: Real-world data from two certified lung cancer centers in Germany

139P The impact of TP53 mutations on EGFR mt+ NSCLC IV patients treated with 3rd generation TKI on 2nd line or further line therapy: Real-world data from two certified lung cancer centers in Germany

Pembrolizumab as First-Line Palliative Therapy in PD-L1 Overexpressing (≥ 50%) NSCLC: Real-world Results with Special Focus on PS ≥ 2, Brain Metastases, and Steroids

IntroductionPembrolizumab is a highly effective standard of care in PD-L1 overexpressing (≥ 50%) non–small-cell lung cancer. However, a substantial share of patients from everyday clinical practice is treated without clear evidence from clinical trials. Patients and MethodsWe performed a retrospective multicentric study including all consecutive patients from 6 certified lung cancer centers in Berlin, Germany, having received pembrolizumab as first-line palliative therapy from January 1 until December 31, 2017. Aims were to validate published clinical trials with a special focus on efficacy and outcome in patients with reduced performance status (PS), brain metastases, and steroids. ResultsA total of 153 patients were included (median age 69 years, 58% men, 69% adenocarcinoma). Rates for PS ≥ 2, brain metastases, and steroids were 24.8%, 20.9%, and 24.2%, respectively. Median objective response rate, progression-free and overall survival were 48.5%, 8.2 and 22.0 months for all patients and 52.4%, 8.8 and 29.2 months in patients fulfilling the inclusion criteria for the KEYNOTE-024 trial. Patients with a comorbidity-defined PS ≥ 2, symptomatic brain metastases requiring upfront radiotherapy, or baseline steroids had significantly reduced survival. In contrast, durable responses occurred with a tumor-related PS ≥ 2 or asymptomatic brain metastases. Grade 3/4 and 5 immune-related adverse events affected 13.7% and 2.0% of patients. ConclusionReal-world and clinical trial efficacy with upfront pembrolizumab correspond well. Pembrolizumab may sufficiently control asymptomatic brain metastases and may improve a cancer-related reduced PS. However, the frail share of patients with a comorbidity-defined PS ≥ 2, symptomatic brain metastases, or baseline steroids derives no relevant benefit.

KRASG12C/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma.

BackgroundPembrolizumab is a standard of care as first line palliative therapy in PD-L1 overexpressing (≥50%) non-small cell lung cancer (NSCLC). This study aimed at the identification of KRAS and TP53-defined mutational subgroups in the PD-L1 high population to distinguish long-term responders from those with limited benefit.MethodsIn this retrospective, observational study, patients from 4 certified lung cancer centers in Berlin, Germany, having received pembrolizumab monotherapy as first line palliative treatment for lung adenocarcinoma (LuAD) from 2017 to 2018, with PD-L1 expression status and targeted NGS data available, were evaluated.ResultsA total of 119 patients were included. Rates for KRAS, TP53 and combined mutations were 52.1%, 47.1% and 21.9%, respectively, with no association given between KRAS and TP53 mutations (P=0.24). By trend, PD-L1 expression was higher in KRAS-positive patients (75% vs. 65%, P=0.13). Objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) in the KRASG12C group (n=32, 51.6%) were 63.3%, 19.8 months (mo.) and not estimable (NE), respectively. Results in KRASother and wild type patients were similar and by far lower (42.7%, P=0.06; 6.2 mo., P<0.001; 23.4 mo., P=0.08). TP53 mutations alone had no impact on response and survival. However, KRASG12C/TP53 co-mutations (n=12) defined a subset of long-term responders (ORR 100.0%, PFS 33.3 mo., OS NE). In contrast, patients with KRASother/TP53 mutations showed a dismal prognosis (ORR 27.3%, P=0.002; PFS 3.9 mo., P=0.001, OS 9.7 mo., P=0.02).ConclusionsA comprehensive assessment of KRAS subtypes and TP53 mutations allows a highly relevant prognostic differentiation of patients with metastatic, PD-L1 high LuAD treated upfront with pembrolizumab.

Differences in therapy and survival between lung cancer patients treated in hospitals with high and low patient case volume

BackgroundIn light of political discussions about minimum case volumes and certified lung cancer centers, this observational study investigates differences in therapy and survival between high vs. low patient volume hospitals (HPVH vs. LPVH). MethodsWe identified 12,374 lung cancer patients treated in HPVH (>67 patients) and LPVH in 2013 from German health insurance claims. Stratified by metastasis status (no metastases, nodal metastases, systemic metastases), we compared HPVHs and LPVHs regarding likelihood of resection and systemic therapy, type of systemic therapy, and surgical outcomes, using multivariate logistic models. Three-year survival was modeled using Cox regression. We adjusted all regression models for age, gender, comorbidity, and residence area, and included a cluster variable for the hospital. ResultsAround 24 % of patients were treated in HPVHs. Irrespective of stratum and subgroup, three-year survival was significantly better in HPVHs. In patients with systemic metastases (OR = 1.84, CI=[1.22,2.76]) and without metastases (OR = 3.28, CI=[2.13, 5.04]), resection was more likely in HPVHs. Among patients with systemic therapy, the odds of receiving pemetrexed was higher in HPVHs, in patients with nodal metastases (OR = 1.57, CI=[1.01,2.45]). In resected patients without metastases the odds ratio of receiving a thoracoscopic lobectomy was 2.28 (CI=[1.04,4.99]) in HPVHs. ConclusionOur data suggests that case volume is clinically relevant in resected and non-resected lung cancer patients, but optimal minimum case volumes may differ for subgroups.

1499P - Pembrolizumab as first-line treatment in NSCLC with PD-L1 ≥50%: Real life results from an all-comer population

BackgroundFirst-line therapy with pembrolizumab is the standard of care in locally advanced and metastatic non-small cell lung cancer (NSCLC) with a PD-L1 expression of≥50%. However, efficacy results in patients with a PS≥2, untreated brain metastases or permanent oral steroids are lacking. MethodsPatients from six certified lung cancer centers in Berlin, Germany, presenting with stage III (non resectable, not suitable for chemoradiation) and IV NSCLC, with a PD-L1 expression of≥50%, diagnosed or treated between January 1st, 2017 and December 31, 2017 were included in this retrospective study. Progression-free (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox regression analyses were used to identify prognostic factors for survival. Values are given as median (range). ResultsDuring the observation period, 128 patients fulfilled the inclusion criteria. Median age was 68.6 years (39 – 85), 76 patients were male (59.4%). Histology was predominantly non-squamous (68.8%). 31 patients (24.2%) had an initial PS of≥2. Oral steroids for ≥2 weeks (equivalent daily doses of≥10mg of prednisolone during therapy with pembrolizumab) were prescribed to 34 patients (26.6%). Pembrolizumab was initiated in 24 patients with previously untreated brain metastases (18.8%). Within a follow-up of 13.0 months (95% CI, 10.5 – 15.4), a median of 9 cycles (1 – 38) were administered corresponding to a duration of treatment of 6.9 months (95% CI, 4.6 – 9.2). Therapy was still ongoing in 30 patients (23.4%). PFS was 9.4 months (95% CI, 4.8 – 14.1) with a duration of response of 11.9 months (95%CI, 8.4 – 15.4). OS reached 18.9 months (95% CI, NE – NE). A PS≥2 was associated with a reduced OS (HR 0.43, 95% CI, 0.25 – 0.75, p=0.003), no effects were noted for brain metastases and steroids. ConclusionsOur data from real life practice in an all comer population demonstrate the efficacy of pembrolizumab in NSCLC with a PD-L1 expression of≥50%. Despite a reduced survival in PS≥2, the reached OS of 8.0 months is superior to historic cohorts with cytotoxic chemotherapy. Furthermore, OS was unchanged in case of untreated brain metastases or permanent steroids. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Immuno-Oncological Treatment and Tumor Mass in Non-Small Cell Lung Cancer: Case-Control Analysis of Overall Survival in Routine Clinical Practice

Background: Immuno-oncological (IO) therapies such as PD-1 and PD-L1 antibodies have been introduced in the treatment of advanced non-small cell lung cancer (NSCLC) since 2015 based on randomized trials showing unprecedented advantages in overall survival (OS) with hazard ratios (HRs) between 0.5 and 0.7. The impact of these treatments on OS in routine clinical practice and the role of tumor mass have not been studied. Methods: 557 consecutive patients with inoperable stage III or stage IV NSCLC diagnosed in our certified lung cancer center from 2006 to 2018 were included if they had received at least one line of systemic treatment. OS of immuno-oncologically treated patients (IO patients, n = 144) who received treatment with a PD-1 antibody (nivolumab [n = 77] or pembrolizumab [n = 51]) or a PD-L1 antibody (atezolizumab [n = 4] or durvalumab [n = 12]) was compared to historic controls treated before availability of IO treatment (n = 413) using case-control analysis. IO patients and historic controls were individually matched for stage, performance state, histology, smoking status, gender, age, and initial treatment mode (palliative vs. definitive radio-chemotherapy). Results: Case-control analysis of 91 matched pairs showed significantly longer OS in IO patients compared to historic controls (21.2 vs. 10.9 months, HR 0.526, CI 0.373–0.723). The benefit was more pronounced in patients with lower tumor stage (HR 0.48 [stage III], 0.40 [IVA], 0.63 [IVB]) or smaller tumor size (HR 0.38 [RECIST ≤57 mm], 0.40 [RECIST 58–94 mm], 0.59 [RECIST 95–141 mm], 0.75 [RECIST ≥142 mm]). Conclusions: IO patients showed significant benefit in OS with HRs comparable to those reported in phase III trials. The benefit tended to be greater in patients with lower tumor mass.

121P - Risk of not receiving second-line therapy is high in EGFR mt+ patients: Real-world data of certified lung cancer centers on treatment sequence in EGFR mt+ patients

121P - Risk of not receiving second-line therapy is high in EGFR mt+ patients: Real-world data of certified lung cancer centers on treatment sequence in EGFR mt+ patients

Pathological-anatomical diagnosis according to the German lung cancer guideline 2018

The German S3-guideline on prevention, diagnosis, therapy and follow-up of lung cancer, published in February 2018, expands on the 2010 guideline to include atotal of 19recommendations and statements regarding the "processing of lung resection specimens (tumor resection specimens)", "processing of lymph nodes", "histo-pathological typing and immunophenotype", "extent of tumor growth in resection specimens", "resection margins" or "R-classification", "grade of malignancy (grading)", "regression grading" as well as the "examination of molecular targets". The statements regarding the analysis of molecular targets result from the diagnostic requirements of the current targeted therapy of advanced lung cancer. At the same time, apathological-anatomical diagnosis according to the current S3-guideline fulfills all corresponding requirements in certified lung cancer centers.

1447P - Risk of not receiving second-line therapy is high in EGFR mt+ pts: Real world data of certified lung cancer centers on treatment sequence in EGFR mt+ pts

Background: Recently FLAURA study demonstrated significant PFS and numeric OS benefit for Osimertinib 1st line vs. 1st gen. TKI’s Erlotinib/Gefitinib. The number of pts switching from 1st gen. to 3rd gen. TKI (30%) appeared to be low and it is questionable whether these data represent real world sequencing treatment patterns. Therefore, we investigated the sequence pattern, i.e. the percentage of 2nd line therapy in EGFR mt+ pts in 3 certified lung cancer centers in Germany. Methods: Data of 912 of 1477 pts tested for EGFR mutations were analyzed between 2009-2017. 140/144 pts with an activating EGFR mt + (16%) and treated with systemic therapy (4 pts received no therapy) were identified and their treatments were captured as well as their outcome. 36 pts were treated before accessibility to 3rd generation TKI and 104 pts after accessibility to 3rd generation TKI. Results: 130/140 pts were treated with 1st line TKI and 10 received 1st line chemotherapy. 17 pts are still on 1st line TKI, 8 pts were lost to follow-up, 3 pts died while on 1st line TKI. 112 pts were candidates for 2nd line therapy. 34/112 (30%) of these pts did not receive 2nd line therapy. Causes for not receiving 2nd line therapy were pts refusal (n = 2), bad PS (n = 26) frequently due to CNS metastases, fast progression and death (n = 6). After accessibility of 3rd gen. TKI, 20 of 66 (30%) pts did not receive 2nd line therapy. Median OS of the overall cohort was 27 months (n = 140), median OS of pts receiving 2nd line (n = 78) vs. no 2nd line (n = 62) was 36 vs. 14 months (p < 0.0001). After accessibility of 3rd gen. TKI 30/104 pts (29%) receive a 3rd gen. TKI after 1st line or 2nd line therapy. Median OS of pts receiving (n = 30) and not receiving 3rd gen. TKI (n = 110) was 55 months vs. 22 months (p < 0.0001). Conclusions: In real world, a significant number of pts treated with 1st or 2nd gen. TKI do not reach 2nd line therapy even when 3rd gen. TKI were accessible. Reasons for not receiving 2nd line therapy are in most cases deterioration of PS and lack of possibility to test for T790M in the minority of cases (n = 28/66, 42% were not tested). These data, although favorable for the small and very selected cohort of pts treated with Osimertinib, might argue for the most effective therapy in 1st line for pts with EGFR mt+ tumors. Legal entity responsible for the study: Carl von Ossietzky University Oldenburg Department of Internal Medicine-Oncology. Funding: Has not received any funding. Disclosure: J. Roeper: Advisory boards: Roche, Boehringer Ingelheim. M. Falk: Advisory boards: Boehringer Ingelheim, Pfizer, Roche. M. Tiemann: Advisory boards: Novartis, Boehringer-Ingelheim, Roche, AstraZeneca; Scientific support: Novartis. F. Griesinger: Advisory boards: Ariad, AstraZeneca, Boehriger-Ingelheim, Bristol-Myers Squibb, Celegene, Clovis, Lilly, Merck-Sharp-Dome, Novartis, Roche; Travel support: Ariad, AstraZeneca, Boehriger Ingelheim, Bristol-Myers Squibb, Celegene, Clovis, Lilly, Merck-Sharp-Dome, Novartis, Pfizer, oche; Scientific support: Ariad, AstraZeneca, Boehriger Ingelheim, Bristol-Myers Squibb, Celegene, Clovis, Lilly, Merck-Sharp-Dome, Novartis, Pfizer, Roche. All other authors have declared no conflicts of interest.

P1.01-82 Risk of Not Receiving 2nd Line Therapy is High in EGFR mt+ pts: Real World Data of Certified Lung Cancer Centers on Treatment Sequence in EGFR mt+ pts

P1.01-82 Risk of Not Receiving 2nd Line Therapy is High in EGFR mt+ pts: Real World Data of Certified Lung Cancer Centers on Treatment Sequence in EGFR mt+ pts

Risk of not receiving 2nd line therapy is high in EGFR mt+ pts: Real world data of certified lung cancer centers on treatment sequence in EGFR mt+ pts.

e21220Background: Recently FLAURA study demonstrated significant PFS and numeric OS benefit for Osimertinib 1st line vs. 1st gen. TKI’s. The number of pts switching from 1st gen. to 3rd gen. TKI (3...

6 years of Certified Lung Cancer Center – The Heidelberg Experience

6 years of Certified Lung Cancer Center – The Heidelberg Experience

Incidence and treatment outcome of EGFR and inactivating P53 alterations in a cohort of 218 consecutively tested patients from a certified lung cancer center

Incidence and treatment outcome of EGFR and inactivating P53 alterations in a cohort of 218 consecutively tested patients from a certified lung cancer center

Incidence of EGFR, kras, BRAF, ALK, and p53 alterations in a cohort of 218 consecutively tested patients from a certified lung cancer center: Correlation with clinical characteristics and treatment outcome.

e19064 Background: The aim of the study was to systematically analyze EGFR, KRAS, BRAF, ALK and p53 within the same cohort of patients, to correlate alterations with clinical characteristics and to...

Second-line chemotherapy exposure in a German cancer society certified lung cancer center: Single-center experience of 4 years and relevance for maintenance therapy.

e19097 Background: One of the strongest rationale for maintenance therapy in NSCLC is the fact that exposure to 2nd line therapy is only 40-60% in clinical trials in specialized treatment centers. Even with follow-up intervals of 6 weeks, the 2nd line treatment rate does not seem to increase. We analyzed the exposure of patients with stage IV NSCLC in one German Cancer Society certified Lung Cancer Center since certification, as long term follow-up data are available. Methods: All primary lung cancer cases stage IV in the lung cancer center were analyzed based on the documentation files between 2009 and 2013. Patients were followed between 1st and 2nd line therapy every 6-8 weeks according to S3 guidelines. Results: 267 patients were diagnosed with NSCLC IV (UICC7), or had systemic relapse of localized disease and were treated with 1st line therapy for metastatic disease. Of these, 168 (63%) received 1st line combination therapy with Carboplatin, 57 (21%) with Cisplatin, 29 (11%) with TKI 1st line therapy...

Incidence of EGFR, KRAS, BRAF, ALK, and p53 alterations in a cohort of 161 consecutively tested patients from a certified lung cancer center, correlation with clinical characteristics and treatment outcome

Incidence of EGFR, KRAS, BRAF, ALK, and p53 alterations in a cohort of 161 consecutively tested patients from a certified lung cancer center, correlation with clinical characteristics and treatment outcome

Second line chemotherapy exposure in a German Cancer Society certified lung cancer center: single center experience of 3 years and relevance for maintenance therapy

Second line chemotherapy exposure in a German Cancer Society certified lung cancer center: single center experience of 3 years and relevance for maintenance therapy