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The purpose of this study is to investigate changes over time in quality of life (QoL) in incurable lung cancer patients and the impact of determinants like molecular alterations (MA).In a prospective, longitudinal, multicentric study, we assessed QoL, symptom burden, psychological distress, unmet needs, and prognostic understanding of patients diagnosed with incurable lung cancer at the time of the diagnosis (T0) and after 3 (T1), 6 (T2) and 12 months (T3) using validated questionnaires like FACT-L, National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT), PHQ-4, SCNS-SF-34, and SEIQoL.Two hundred seventeen patients were enrolled, 22 (10%) with reported MA. QoL scores improved over time, with a significant trend for DT, PHQ-4, and SCNS-SF-34. Significant determinants for stable or improving scores over time were survival 6 months, performance status at the time of diagnosis, and presence of MA. Patients with MA showed better QoL scores (FACT-L at T1 104.4 vs 86.3; at T2 107.5 vs 90.0; at T3 100.9 vs 92.8) and lower psychological distress (NCCN DT at T1 3.3 vs 5; at T2 2.7 vs 4.5; at T3 3.7 vs 4.5; PHQ-4 at T1 2.3 vs 4.1; at T2 1.7 vs 3.6; at T3 2.2 vs 3.6), but also a worsening of the scores at 1 year and a higher percentage of inaccurate prognostic understanding (27 vs 17%) compared to patients without MA.Patients with tumors harboring MA are at risk of QoL deterioration during the course of the disease. Physicians should adapt their communication strategies in order to maintain or improve QoL.

Background Although current guidelines advocate early integration of palliative care, symptom burden and palliative care needs of patients at diagnosis of incurable cancer and along the disease trajectory are understudied. Material and Methods We assessed distress, symptom burden, quality of life, and supportive care needs in patients with newly diagnosed incurable cancer in a prospective longitudinal observational multicenter study. Patients were evaluated using validated self‐report measures (National Comprehensive Cancer Network Distress Thermometer [DT], Functional Assessment of Cancer Therapy [FACT], Schedule for the Evaluation of Individual Quality of Life [SEIQoL‐Q], Patients Health Questionnaire‐4 [PHQ‐4], modified Supportive Care Needs Survey [SCNS‐SF‐34]) at baseline (T0) and at 3 (T1), 6 (T2), and 12 months (T3) follow‐up. Results From October 2014 to October 2016, 500 patients (219 women, 281 men; mean age 64.2 years) were recruited at 20 study sites in Germany following diagnosis of incurable metastatic, locally advanced, or recurrent lung (217), gastrointestinal (156), head and neck (55), gynecological (57), and skin (15) cancer. Patients reported significant distress (DT score ≥ 5) after diagnosis, which significantly decreased over time (T0: 67.2%, T1: 51.7%, T2: 47.9%, T3: 48.7%). The spectrum of reported symptoms was broad, with considerable variety between and within the cancer groups. Anxiety and depressiveness were most prevalent early in the disease course (T0: 30.8%, T1: 20.1%, T2: 14.7%, T3: 16.9%). The number of patients reporting unmet supportive care needs decreased over time (T0: 71.8 %, T1: 61.6%, T2: 58.1%, T3: 55.3%). Conclusion Our study confirms a variable and mostly high symptom burden at the time of diagnosis of incurable cancer, suggesting early screening by using standardized tools and underlining the usefulness of early palliative care. Implications for Practice A better understanding of symptom burden and palliative care needs of patients with newly diagnosed incurable cancer may guide clinical practice and help to improve the quality of palliative care services. The results of this study provide important information for establishing palliative care programs and related guidelines. Distress, symptom burden, and the need for support vary and are often high at the time of diagnosis. These findings underscore the need for implementation of symptom screening as well as early palliative care services, starting at the time of diagnosis of incurable cancer and tailored according to patients’ needs., Guidelines recommend early integration of palliative care in the treatment of patients with advanced cancer. This study assessed distress, symptom burden, quality of life, and supportive care needs in patients with newly diagnosed incurable cancer to facilitate future implementation of more effective palliative care services.

Background: Little is known on symptom burden, psychosocial needs, and perception of prognosis in advanced lung cancer patients at the time of diagnosis, although early assessment is strongly recommended within the setting of daily routine care. Methods: Twelve study sites cross-sectionally assessed symptoms and psychosocial needs of patients suffering from newly diagnosed incurable lung cancer. Assessment comprised NCCN distress thermometer, FACT-L, SEIQoL-Q, PHQ-4, and shortened and modified SCNS-SF-34 questionnaires. Additional prognostic information from both patients and physicians were collected. Results: A total of 208 patients were evaluated. Mean age was 63.6 years, 58% were male, 84% suffered from stage IV lung cancer, and 71% had an ECOG performance status of 0–1. Mean distress level was 5.4 (SD 2.5), FACT-L total score was 86 (21.5), and TOI 50.5 (14.9). PHQ-4 was 4.6 (3.3), and shortened and modified SCNS-SF-34 showed 9 (8.7) unmet needs per patient. According to their physicians’ perspective, 98.1% of patients were reflecting on and 85.2% were accepting incurability, while 26.5% of patients considered the treatment to be of curative intent. Conclusion: Our findings emphasize substantial domains of symptom burden seen in newly diagnosed, incurable lung cancer patients. Oncologists should be aware of these features and address prognostic issues early in the disease trajectory to facilitate opportunities to improve coping, advance care planning, and appropriate integration of palliative care, thus improving quality of life.

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

7501 Background: This multicenter, randomized, phase III study compared B-R and CHOP-R as first-line treatment in patients (pts) with indolent lymphomas or mantle cell lymphoma and was first published in The Lancet in 2013. The final analysis demonstrated a significantly prolonged progression-free survival (PFS) in the B-R group compared to the CHOP-R group, with a median PFS of 69.5 vs. 31.2 months, respectively. In the current analysis, we present updated results for overall survival (OS), time-to-next-treatment (TTNT), and secondary malignancies (sNPL) with a median follow-up of 113 months for patients with indolent lymphomas (excluding MCL). Methods: 447 pts with indolent lymphomas were randomized to receive B-R or CHOP-R for a maximum of 6 cycles. The primary endpoint was PFS; secondary endpoints included OS, TTNT, and sNPL. Results: Patient characteristics were well balanced between arms; median age was 64 years. The difference in OS between the two treatment arms was not statistically significant, with 60 deaths in the B-R group vs 68 deaths with CHOP-R (HR 0.82, 95% CI 0.58 – 1.15, p = 0.249). The estimated 10-year survival rates were 71% for B-R and 66% for CHOP-R. TTNT was significantly prolonged with B-R compared with CHOP-R (HR 0.52, 95% CI 0.38 – 0.69, p < 0.001). Median TTNT was not yet reached in the B-R group (95% CI 124.9 – n.y.r) vs. 56 months in the CHOP-R group (95% CI 39.1 – 82.0). Patients treated initially with B-R needed fewer second-line treatments due to disease progression compared to CHOP-R treated pts: 73 pts (34%) in the B-R group received salvage treatment compared with 106 pts (52%) in the CHOP-R group. For B-R pts, CHOP-R was used as second-line therapy 26 times (36%), whereas B-R was used for pts initially treated with CHOP-R 49 times (46%). 36 pts with sNPL were observed in the B-R group compared with 39 in the CHOP-R group, with 7 hematological malignancies in both groups to date. Conclusions: In pts with previously untreated indolent lymphomas, B-R demonstrates a PFS and TTNT benefit over CHOP-R. Clinical trial information: NCT00991211.

Bendamustine is an alkylating agent with high efficacy in non-Hodgkin's lymphoma and multiple myeloma. Even in solid tumours, monotherapy with bendamustine has resulted in subjective remissions and has been associated with a low rate of side effects. The current dose-finding study was designed to determine the maximum tolerated dose (MTD) of combined carboplatin/bendamustine in previously untreated patients with extensive-stage small cell lung cancer (SCLC).Carboplatin was administered as a 1-hour infusion on day 1 at increasing dose levels, and bendamustine was administered as a short infusion on days 1 and 2 at increasing dose levels (80-120 mg/m(2)). The regimen was administered every 3 weeks. Four dose levels were planned, starting with 80 mg/m(2) bendamustine and carboplatin area under the curve (AUC) 5 (dose level I). The other dose levels were 100 mg/m(2) bendamustine and carboplatin AUC 5 (dose level II), 100 mg/m(2) bendamustine and carboplatin AUC 6 (dose level III), and 120 mg/m(2) bendamustine and carboplatin AUC 6 (dose level IV). A minimum of three patients were enrolled at each dose level.Dose-limiting toxicities, which included fatigue, infection and tachyarrhythmia, were observed at dose level III. The recommended dose for phase II studies was therefore established at dose level II. The majority of haematological and non-haematological toxicities observed were only mild (grade 1 or 2) in patients at dose levels I and II. None of the patients developed severe alopecia. Objective responses were observed in eight of the ten patients involved in this trial.Because of its acceptable toxicity and favourable preliminary antitumour efficacy, the combination of carboplatin and bendamustine appears to be a potentially useful chemotherapeutic option in patients with extensive SCLC.

Background: Bendamustine is an alkylating agent with hybrid activity and proven efficacy in small-cell lung cancer associated with a favorable toxicity rate. This phase II study of carboplatin/bendamustine was conducted to evaluate the efficacy of this combination in patients with extensive disease small-cell lung cancer (ED-SCLC). Methods: Fifty-six untreated patients with ED-SCLC were enrolled. Their median age was 63 years. Sixty-seven percent of patients were male and 18% had a World Health Organization performance status of 2. Bendamustine was administered as a 30- to 60-minute infusion at a dose of 80 mg/m 2 on days 1 and 2, and carboplatin was given at an area under the curve of 5 on day 1 of a 21-day cycle. Results: Fifty-five patients were assessable for response and toxicity. The overall response rate was 72.7% (95% confidence interval: 59%–84%), with one complete remission (1.8%). The median time to progression was 5.2 months (95% confidence interval: 4.2–5.6). At the time of evaluation, 71% of the patients had died. The median survival time reached 8.3 months (95% confidence interval: 6.6–9.9). The major toxicity of this regimen was myelosuppression, including grade 3 or 4 neutropenia (46%), thrombopenia (26%), anemia (15%), and infections (11%). Toxic death was recorded in two patients (3.6%). Conclusions: The carboplatin/bendamustine regimen is a well-tolerated cytostatic combination in ED-SCLC with activity comparable with that of other platinum-based regimens. Further investigations, such as a phase III trial, are currently planned.

Background: This multicenter, randomized, phase III study compared B-R and CHOP-R as first-line treatment in patients (pts) with indolent lymphomas or MCL and was presented at ASH 2009, ASCO 2012, and published in The Lancet in 2013. The final published analysis at a median follow-up of 45 months demonstrated a significantly prolonged progression-free survival (PFS) in the B-R group, compared to the CHOP-R group (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.44–0.74; p Methods: 549 pts with indolent lymphomas or MCL were randomized to receive B-R or CHOP-R for a maximum of 6 cycles. The primary endpoint was PFS; secondary endpoints included OS, TTNT, and sNPL. Results: 514 randomized pts were evaluable (261 B-R; 253 CHOP-R). Patient characteristics were well balanced between arms; median age was 64 years. Fewer pts treated initially with B-R needed second-line treatments due to disease progression compared to CHOP-R treated pts: 93 pts (36%) in the B-R group received salvage treatment compared with 140 pts (55%) in the CHOP-R group. Of those in the CHOP-R group, 69 pts (49%) received B-R as salvage. TTNT was significantly prolonged with B-R compared with CHOP-R (HR 0.53, 95% CI 0.40-0.68; p The difference in complete response (CR) rates (independent of treatment arms) between male (n=272, median age 63 years) and female (n=242, median age 64 years) pts was statistically significant: 28.6% for male pts versus 42.1% for female pts (p=0.0016). Female pts had a longer median TTNT compared to male pts (not yet reached vs. 52.2 months, respectively; HR 0.70, 95% CI 0.54-0.90; p=0.006). The achievement of a CR was associated with significantly prolonged OS, with an estimated 10-year survival rate of 72.6% for pts with a CR and 63.6% for pts with a partial response (p=0.006). The difference in OS between the treatment arms was not statistically significant, with 65 and 76 deaths in the B-R and CHOP-R arms, respectively. The estimated 10-year survival rates were 67.4% for B-R and 60.1% for CHOP-R (p=0.262). In pts with indolent lymphomas (total group without MCL), there was a trend toward longer survival for the B-R group compared with the CHOP-R group, with 43 deaths out of 215 pts (20.0%) in B-R and 58 deaths out of 205 pts (28.3%) in CHOP-R. The estimated 10-year survival rates for pts with indolent lymphomas were 71.9% for B-R and 61.5% for CHOP-R (HR 0.70, 95% CI 0.48-1.04; p=0.076). No difference in OS was found in the subgroup of pts with MCL (n=95) (HR 1.28, 95% CI 0.69-2.39; p=0.429). Twenty sNPL were observed in the B-R group compared with 23 in the CHOP-R group, with 1 hematological malignancy in each group (1 MDS in B-R, 1 AML in CHOP-R) to date. Updated sNPL results will be presented at the ASH meeting. Conclusions: In pts with previously untreated indolent lymphomas, and in elderly pts with MCL, B-R demonstrates a PFS and TTNT benefit over CHOP-R. OS for the entire group of patients was not significantly different while treatment with B-R resulted in a trend toward survival benefit in the group of pts with indolent lymphomas. Disclosures Off Label Use: Indication and dosage of bendamustine.

Introduction: Fludarabine plus rituximab (F-R) is an established treatment option for patients (pts) with relapsed/refractory follicular lymphoma (FL), other indolent lymphoma, or mantle cell lymphoma (MCL). To further improve the treatment in this setting we initiated in 2003 a multicenter, randomized phase III study to compare the efficacy and safety of bendamustine plus rituximab (B-R) versus F-R for pts with relapsed FL, other indolent lymphomas or MCL. Patients and Methods: 230 pts in need of treatment were randomized to rituximab 375 mg/m² (day 1) plus either bendamustine 90 mg/m² (days 1+2) or fludarabine 25 mg/m² (days 1–3) q 28 days for a maximum of 6 cycles. Prophylactic use of antibiotics or granulocyte-colony stimulating factor (G-CSF) was not generally recommended; however, in case of severe granulocytopenia, G-CSF use was permitted. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), overall response rate (ORR), and complete response rate (CR). The protocol was amended in 2006 to allow rituximab maintenance therapy (rituximab 375 mg/m2 q 3 months for up to 2 years) in both arms, following regulatory approvals in this setting. Results: A total of 219 pts were evaluable for the analysis (114 B-R; 105 F-R). There were no significant differences between arms for patient characteristics, including age, stage, LDH, IPI, FLIPI, bone marrow infiltration, and extranodal involvement. Most pts had stage IV (71.6% B-R; 60.6% F-R) or stage III disease (21.1% B-R; 25.3% F-R). Median patient age was 68 yrs (range 38–87). Patients had received a median of 1 prior therapy (range 1–7). Histological subtypes were distributed equally between the B-R and F-R arms: follicular, 45.9% and 47.5%, respectively; Waldenström’s Macroglobulinemia, 11.9% and 11.1%; MCL, 20.2% and 21.2%; other indolent lymphomas, 23% and 20.2%. A median of 6 cycles were given in both treatment arms, with 75.2% and 53.4% of B-R and F-R pts receiving 6 cycles, respectively. At the time of this analysis (June 2014), the median observation time was 96 months. The ORR was significantly higher with B-R than with F-R (83.5% vs. 52.5%, respectively; p< 0.0001). The CR rate with B-R was also significantly higher than that with F-R (38.5% vs. 16.2%; p=0.0004). Median PFS was significantly prolonged with B-R compared with F-R (34 vs. 12 months; hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.38–0.72; p There were no significant differences in the rates of alopecia, stomatitis, erythema, allergic reactions, peripheral neuropathy, or infectious episodes between groups. Hematologic toxicities were also similar between arms: 8.9% grade 3/4 neutropenia with B-R vs. 9.1% with F-R; 11.8% grade 3/4 leukocytopenia with B-R vs. 12.4% with F-R. The overall incidence of serious adverse events was similar for the B-R and F-R groups (17.4% and 22.2%, respectively). 17 pts (14.9%) developed a secondary neoplasia after B-R compared with 16 pts (15.2%) after F-R. Of these, 5 pts in the B-R group, and 3 pts in the F-R group developed a secondary hematological neoplasia (2 AML [1 AML M4], 1 CML, 1 DLBCL, and 1 HD after B-R; and 2 AML M4, and 1 MDS after F-R). An unplanned subanalysis showed that rituximab maintenance therapy significantly prolonged overall survival (HR 0.38, 95% CI 0.32-0.71; p=0.0003) and PFS (HR 0.35, 95% CI 0.31-0.62; p< 0.0001) in the small group of 40 pts who received this treatment (23 B-R, 17 F-R) compared with those who did not. Although the numbers are too small in this non-randomized comparison to draw validated conclusions, these results appear to confirm the favorable role of rituximab maintenance. Conclusions: B-R was more effective than F-R in this setting of relapsed FL, other indolent lymphomas and MCL due to higher overall and complete response rates, a longer PFS, and an improved OS. These data confirm the high anti-lymphoma activity of B-R. Disclosures Off Label Use: Indication and dosage of bendamustine.

Low-grade non-Hodgkin's lymphomas (NHL) are very sensitive to a broad range of chemotherapeutic and biological agents. Relapses, however, occur even after aggressive cytostatic combinations in first-line therapy. Therefore, effective and well-tolerated salvage therapies are very important. In this single-institution trial, the efficacy and toxicity of bendamustine in the treatment of relapsed low-grade NHL was investigated. Fifty-eight patients with low-grade NHL pretreated with different cytostatic regimens were included. All patients received bendamustine at 120 mg/m(2) as a 1-h infusion on 2 consecutive days. The treatment was repeated every 3 weeks until complete remission (CR), partial remission (PR) or stable disease (SD) was confirmed on two consecutive cycles. Efficacy and toxicity were evaluated in 52 patients: CR was induced in 11%, PR in 62% and SD in another 10% of the patients. No response to treatment was seen in 17%. The median duration of remission was 16 months and the median survival time was 36 months. Side effects were generally mild, and restricted to myelosuppression, gastrointestinal toxicity and allergic reactions. Bendamustine proved to be very effective and was well tolerated in pretreated patients with relapsed or primary resistant low-grade NHL.

The observations reported here support the hypothesis that 5-FU induces a reversible cardiopathy (having a common final pathway with ischemia), including myocardial dysfunction, with a potentially fatal course. Although a clear dose-response relation is not evident, the incidence seems to be increased with recently promoted 24-hour high-dose 5-FU/ folinic acid combination therapy. There may be a cumulative “threshold dose” of 1,500 to 7,000 mg. To date, predisposing factors as well as a reliable treatment and prophylaxis are not well defined.

In cancer patients, hypersensitivity reactions to adjunctive medications are easily mistaken for cytostatic toxicities. We report on three patients with systemic reactions (flush, dyspnea, tachycardia, hypotension, back pain) to a lipid emulsion containing long chain fatty acids (LCT). Reexposure to LCT and exposure to MCT (medium chain fatty acids) solutions of slightly different composition – no soybean lecithin used as an emulsifier – were well tolerated. These data suggest that traces of soybean proteins are the allergenic agents. Therefore, hypersensitivity to concomitant medications, including parenteral nutrition, has to be considered in oncologic patients demonstrating severe systemic reactions to intravenous therapy.