Lungenkarzinom (inkl. Pleura) III

V52 Tepotinib-Behandlung von Patienten mit MET-Exon 14 Skipping (METex14)-Mutationen des Nicht-kleinzelligen Lungenkarzinoms: Ergebnisse von allen Patienten der Kohorte A der VISION-Studie
Michael Thomas, Heidelberg, D

Introduction: In the primary analysis of the Phase II VISION study, tepotinib demonstrated durable efficacy and a tolerable safety profile in pts with METex14 skipping non-small cell lung cancer (NSCLC), as identified by liquid and/or tissue biopsy. Here, we report updated efficacy outcomes in all pts across treatment lines.

Methods: Pts with advanced, EGFR/ALK wild-type, METex14 skipping NSCLC received oral tepotinib 500 mg once daily. All pts who received tepotinib in Cohorts A (enrollment complete) + C (ongoing) were assessed for safety; pts in Cohort A were assessed for efficacy. Primary endpoint was objective response (OR) assessed by independent review committee (IRC). Secondary endpoints included duration of response (DOR) and safety.

Results: 152 pts were enrolled (including 15 pts in Germany); pts were elderly (median 73.1 years), half were male (52.0%), half had smoking history (52.0%), and most had adenocarcinoma (86.2%). In pts with 1 (n=49) or ≥2 (n=34) prior treatments, best OR across all prior therapies were two complete responses (2.4%) and 24 partial responses (28.9%) with a median longest DOR of 7 months (range 1-17).

As of July 1, 2020, objective response rate (ORR) was 44.7% (95% CI: 36.7, 53.0), and median DOR was 11.1 months (95% CI: 8.4, 18.5). Efficacy was consistent between treatment-naïve (n=69) and previously treated (n=83) pts (Table). Pts with brain mets (n=23) had a comparable ORR of 47.8% (95% CI: 26.8, 69.4) and a median DOR of 9.5 months (95% CI: 5.5, not estimable).

Safety was assessed in 255 pts. Grade ≥3 treatment-related adverse events (TRAEs) were reported in 64 pts (25.1%). 27 pts (10.6%) discontinued due to TRAEs. The most common TRAE was peripheral edema (138 pts [54.1%] all grades, 19 pts [7.5%] Grade ≥3), which led to treatment discontinuation in 9 pts (3.5%).

Conclusions: Tepotinib showed robust and durable clinical activity across therapy lines, as expected when targeting an oncogenic driver. Peripheral edema was the most common AE; most AEs were mild- moderate with few discontinuations.

V142 5-Jahres-Überlebensdaten mit Durvalumab nach Chemoradiotherapie bei inoperablem NSCLC im Stadium III - ein Update der PACIFIC-Studie
Maike de Wit, Berlin, D

Introduction: In the placebo-controlled Phase 3 PACIFIC trial of patients with unresectable Stage III NSCLC without disease progression after platinum-based concurrent chemoradiotherapy (cCRT), durvalumab significantly improved overall survival (OS; stratified HR 0.68; 95% CI 0.53-0.87; p=0.0025; median not reached vs 28.7 months; data cutoff [DCO], Mar 22, 2018) and progression-free survival (PFS; stratified HR 0.52, 95% CI 0.42-0.65; p< 0.0001; median 16.8 vs 5.6 months; DCO, Feb 13, 2017) based on the DCOs used for the primary analyses. Durvalumab was associated with manageable safety and did not detrimentally affect patient-reported outcomes compared with placebo. These findings established consolidation durvalumab after CRT (the 'PACIFIC regimen') as the standard of care in this setting. We will report updated, exploratory analyses of OS and PFS assessed ~5 years after the last patient was randomized.

Methods: Patients with WHO PS 0/1 (any tumor PD-L1 status) whose disease did not progress after platinum-based cCRT (≥2 cycles) were randomized (2:1) 1-42 days following cCRT (total prescription RT dose typically 60-66 Gy in 30-33 fractions) to receive 12 months' durvalumab (10 mg/kg IV every 2 weeks) or placebo, stratified by age (< 65 vs ≥65 years), sex, and smoking history (current/former smoker vs never smoked). Primary endpoints were OS and PFS (blinded independent central review; RECIST v1.1) in the ITT population. We will present updated analyses of OS and PFS for the ITT population (with HRs and 95% CIs estimated from stratified log-rank tests), and for pre-specified and post-hoc patient subgroups (unstratified Cox proportional hazards models), based on 5-year follow-up data from PACIFIC. Medians and OS/PFS rates will be estimated with the Kaplan-Meier method.

Results: Updated OS and PFS data, including relevant subgroups, 5-year OS/PFS rates, and an updated summary of subsequent anti-cancer therapy, based upon a DCO of Jan 11, 2021 will be presented.

Conclusion: The updated survival outcomes from the PACIFIC trial will provide insight into long-term survival benefit with durvalumab following cCRT.

Encore of ASCO 2021 presentation. Funded by AstraZeneca.


V238 Zweitlinientherapie mit nintedanib + docetaxel beim fortgeschrittenen Adenokarzinom der Lunge nach kombinierter Erstlinien-Chemo-Immuntherapie: Aktualisierte Effektivitäts- & Sicherheitsdaten aus der

Christian Grohé, Berlin, D

Background: Treatment strategies for patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations have changed significantly during the last decade. Immune checkpoint inhibitors (ICIs), with or without chemotherapy, have become the first-line (1L) standard of care. Limited clinical data is available to help guide treatment decisions for treatment post-progression. Nintedanib (Vargatef®) is an oral triple angiokinase inhibitor targeting the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) pathways. It is approved in the EU and other countries in combination with docetaxel for the treatment of advanced adenocarcinoma NSCLC after progression on 1L chemotherapy.

Methods: This updated analysis is part of the ongoing, prospective, non-interventional VARGADO study (NCT02392455) of nintedanib plus docetaxel. The current analysis includes efficacy and safety results from 137 patients (pts) with adenocarcinoma NSCLC who received second-line (2L) nintedanib plus docetaxel after prior 1L chemo-ICI treatment (Cohort C).

Results: In this cohort, the median age was 63 years (range: 37-84); 80 pts (58.4%) were men, and 98 pts (71.5%) had an ECOG PS 0/1. 127 pts (92.7%) had received prior 1L pembrolizumab-based combination therapy. Objective response rate with 2L nintedanib plus docetaxel was 37.5% (30/80 pts), disease control rate was 72.5% (58/80 pts), and median progression-free survival was 4.8 months (95% confidence interval: 3.7-6.6). Grade ≥3 treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation were observed in 62 pts (45.3%), 50 pts (36.5%) and 40 pts (29.2%), respectively.

Conclusions: These results suggest that 2L nintedanib plus docetaxel represents an effective treatment option with a manageable safety profile in pts with advanced adenocarcinoma NSCLC following progression on 1L chemo-immunotherapy.


V286 Patienten-relevante Ergebnisse bei mit Capmatinib behandelten Patienten mit METex14-mutiertem fortgeschrittenen NSCLC: Ergebnisse aus der Phase-2-Studie GEOMETRY mono-1
Jürgen Wolf, Köln, D

Capmatinib showed substantial antitumor activity and manageable tolerability in patients with MET ex14-mutated advanced NSCLC in the GEOMETRY mono-1 trial. PROs from this study are reported here. GEOMETRY mono-1 enrolled patients with METex14-mutated or MET-amplified NSCLC to receive capmatinib. Here we report results for patients with METex14 mutations. PROs were collected at baseline (BL) and every 6 Wks until end of treatment. Key PROs included change from BL in QLQ-C30 global

health status (GHS), QLQ-LC13 symptoms (cough, chest pain and dyspnea), and EQ-5D-5L visual analogue scale (VAS), with a ≥10-point change from BL considered clinically meaningful. TTDD in QLQ- LC13 symptoms (time from treatment initiation to first date of ≥10% symptom change from BL with no later reduction) was assessed using Kaplan-Meier. QLQ-LC13 symptoms over time were explored by BIRC- assessed clinical response to capmatinib.

By Jan 6, 2020 cut-off, median capmatinib exposure was 48.2 (4.0-117.4) Wks and 22.1 (0.4-136.0) Wks for 1L and 2L+ patients, respectively. A total of 27/28 1L patients and 65/69 2L+ patients completed PROs at BL, and completion rate remained high (mostly >70%) through treatment cycles. Mean [SD] BL PRO scores were moderate-to-high in 1L and 2L+ patients (GHS: 64.7 [21.6] and 58.8 [21.0.]; cough: 35.9 [32.6] and 28.7 [28.2]; chest pain: 12.8 [23.2] and 17.2 [22.7]; dyspnea: 23.5 [23.4] and 22.2 [20.8], VAS: 67.7 [20.8] and 61.9 [18.8], respectively). Overall change from BL in PROs was maintained over time. Cough improved early, with meaningful improvements observed through cycles, notably in 1L patients (mean change from BL [SD] at Wk 7: 1L -13.0 [39.9], 2L+ -8.2 [28.4]; Wk 25: 1L -15.6 [33.0], 2L+ -6.0 [31.5]; Wk 43: 1L -28.2 [26.7], 2L+ -10.5 [27.3]). Median TTDD in GHS was 16.6 months (mo) (95% CI: 9.7, NE [not estimated]) and 12.4 mo (95% CI: 4.2, 19.4) in 1L and 2L+ patients, respectively. Median TTDD for cough and chest pain was NE in both 1L and 2L+ patients, and for dyspnea was 19.4 mo (95% CI: 12.4, NE) and 22.1 mo (95% CI: 9.9, NE), respectively. QLQ-LC13 symptoms improved at all cycles in patients achieving clinical complete response or partial response, while symptom worsening was seen in those with no clinical response.

Capmatinib was associated with clinically meaningful improvements in cough, delayed time to lung symptom deterioration, and preserved QoL, supporting its use as a treatment option in patients with METex14-mutated NSCLC.


V294 Checkpoint Inhibitor Monotherapie bei potentiell studientauglichen und nicht-tauglichen NSCLC Patienten - Real World Daten der deutschen CRISP Registerplattform (AIO-TRK -0315)
Frank Griesinger, Oldenburg, D

Introduction: Treatment for metastatic non-small cell lung cancer (NSCLC) stratified according to biomarker testing results was shown in clinical trials to have beneficial outcomes (out). Whether these improvements carry over into real-world routine therapy is of great interest for patients (pts) and physicians. Here we used the prospective, national clinical research platform CRISP to compare patient characteristics (chr) and out of pts with PD-L1 TPS≥50% tumours treated with checkpoint inhibitor monotherapy (CPI) who are deemed either potentially study-eligible (se) or non-study-eligible (n-se).

Methods: CRISP (NCT02622581) is a prospective, observational, open, multicentre, interdisciplinary clinical research platform that collects data on all (sequential) treatments, patient and tumour chr, biomarker testing, clinical and patient-reported out in ~180 hospitals and practices in Germany. Currently 6300+ pts were recruited, who will be followed until death or end of project. Data from 493 pts with PD-L1 TPS≥50% recruited between 12/2015 and 06/2019 and receiving CPI as 1st-line treatment was analysed. Pts were deemed se if they had the following chr: ECOG=0-1, Stage IV, no brain metastases, no HIV or second tumour and no prior (neo-)adjuvant therapies.

Results: Of 493 analysed pts 191 pts were potentially se in reflection of inclusion criteria for clinical trials KEYNOTE 42 and 24, 282 pts were n-se representing the real-world pts population. Although both groups are similar in age (median 68 years, both) and CR/PR rates were comparable (1%[se] vs. 2%[n- se] and 21% vs. 22%) as well as rates of stopped treatments because of toxicity (10%, both), potentially se pts. had a longer PFS (10.0 months, 95% CI: 7.6-15.2 vs. 7.9 months, 95% CI: 6.0-10.6) and OS (23.3 months, 95% CI: 16.5-26.1 vs. 20.2 months, 95% CI: 15.9-26.2) than potentially n-se pts.

Conclusion: In recent years the use of CPI monotherapy in PD-L1 TPS≥50% pts increased in Germany, resulting in improved treatment out. Potentially study-eligible pts are profiting more than potentially non- study-eligible pts. The impact of CPI combination therapies or treatment without CPI on both pts groups, will be subject of future analyses.