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Background The prognosis of patients with recurrent small cell lung cancer (SCLC) remains poor and treatment options are limited. We performed a multi-institution retrospective cohort study to evaluate the outcome of thoracic reirradiation, identify prognostic factors and assess treatment-related toxicity. Methods Data of 33 patients re-irradiated for recurrent SCLC at 4 international university hospitals, were analysed. Overall survival (OS) acute and late toxicities were evaluated and prognostic factors for reirradiation were identified. Results Reirradiation (Re-RT) was performed at a median interval time of 24 months after the first thoracic radiotherapy series. Median survival after reirradiation was 7 months (range, 1-54 months). The Re-RT dose in EQD2 ranged from 20 to 87.50 Gy with a median of 32.50 Gy. The 1- and 2-year OS were 33% and 17%, respectively. Patients with a good performance status (KPS >70%), absence of extrathoracic disease, reirradiation dose (EQD2) of >40 Gy and a cumulative dose of first plus second series of radiotherapy (EQD2) >90 Gy were associated with improved OS. Acute pulmonary Grade 1-2 toxicity from re-irradiation was recorded in 11 patients (33%) and grade 3 acute toxicity was encountered 1 patient (3%). Conclusions Reirradiation for locoregionally recurrent SCLC is safe and shows promising outcomes. Patients reirradiated with doses >40 Gy experienced more favourable survival rates. In contrast, patients with a poor performance status or extrathoracic disease have a poor prognosis and Re-RT should be considered only for symptom control in this group.

Background: Irinotecan (CPT-11) can be used as a first-line therapeutic drug against extensive-stage small cell lung cancer (SCLC); it can also be used in second-line treatment for SCLC. CPT-11-induced delayed diarrhea restricts its clinical application. This study aimed to confirm whether Banxia Xiexin decoction was effective in preventing and controlling CPT-11-induced delayed diarrhea. Methods: A total of 27 patients with recurrent SCLC undergoing chemotherapy regimens including CPT-11 were enrolled for the study. UGT1A1*28, UGTlAl*6, ABCB1*2, and SLCO1B1*15 gene polymorphisms were detected. If delayed diarrhea occurred in the first cycle of chemotherapy, Banxia Xiexin decoction was orally administered for 5 consecutive days starting 1 day before the second cycle of chemotherapy to prevent and control the delayed diarrhea. The objective response, overall survival, and toxicity were recorded. Results: Complete response, partial response, and stable disease were observed in none, 6, and 10 patients, respectively. Delayed diarrhea occurred in 6 patients, and 4 of 5 patients were relieved or controlled using Banxia Xiexin decoction. The median overall survival was 6 months. Conclusion: Banxia Xiexin decoction appeared to prevent and control delayed diarrhea induced by CPT-11 in this small observational study, and further study with a larger sample size, including potentially randomized trials, is suggested.

e20591 Background: The main aim of this study was to evaluate the efficiency of albumin-bound paclitaxel (nab-PTX) plus PD-1/PD-L1 inhibitor versus second-line chemotherapy in small cell lung cancer (SCLC) patients who have failure to the first-line standard treatment. Methods: We retrospectively collected patients’ data from medical records between January 2015 to July 2020 in Shandong Cancer Hospital and Institute. Consecutive 42 patients who were treated with nab-PTX plus PD-1/PD-L1 inhibitor were enrolled and compared with, 126 patients who received second-line chemotherapy (1:3 matched with patient and tumor characteristics). Progress free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Results: Patients treated with nab-PTX plus immunotherapy group and second-line chemotherapy group achieved the median PFS of 5.6 months and 3.3 months ( p = 0.043), respectively. The median OS were 7.7 months and 6.3 months ( p = 0.021), respectively. The ORR and DCR were also higher in nab-PTX plus PD-1/PD-L1 inhibitor group (ORR: 33.3% vs 20.6%, p = 0.094; DCR: 61.9% vs 41.3%, p = 0.020, respectively). The most common incidences of grade ≥3 adverse events were leukopenia and neutropenia, there were no significance difference between the two groups. Conclusions: Albumin-bound paclitaxel plus PD-1/PD-L1 inhibitor conferred higher ORR and DCR, and improved PFS and OS in SCLC patients failed with first-line treatment. Further prospective and randomized trial that directly compares the treatments is urgently warranted.

Background: Small cell lung cancer (SCLC) is a type of highly malignant tumor. It is easy to relapse and high resistant to second-line chemotherapy. There is not a standard plan for third-line and subsequent-line treatment, hence the current study aimed to explore the performance of nanoparticle albumin bound paclitaxel (Nab-P) in the third-line treatment of recurrent SCLC. Methods: A retrospective analysis of pathologically confirmed third-line SCLC patients was conducted to observe the efficacy and adverse reactions of Nab-P treatment. Results: Among the 37 SCLC patients included in the study, objective response rate was 24.32%, and disease control rate was 81.08%. The main adverse reactions were gastrointestinal reactions, bone marrow suppression, muscle and joint aches and fatigue. Adverse reactions ≥ level 3 included leukopenia & neutropenia (24.32%), thrombocytopenia (5.41%) and anemia (2.70%). Conclusions: As a single-agent third-line treatment for patients with relapsed SCLC, Nab-P was effective and safe.

Immune checkpoint inhibitors, specifically PD-1–directed agents, have changed the treatment paradigm of non–small cell lung cancer (NSCLC) and are being actively evaluated in patients with small cell lung cancer. After initial studies demonstrated survival advantage with these agents in patients with recurrent NSCLC, these agents now have demonstrated survival advantage in some patients with early-stage NSCLC. Further evaluation of these agents in combination with chemotherapy regimens and other checkpoint inhibitors is ongoing. Recent data suggest that addition of these agents to chemotherapy may improve survival compared with chemotherapy alone. Promising results have also been observed in patients with recurrent small cell lung cancer. Ongoing studies will define the role of these agents in the management of patients with small cell lung cancer. Tumor PD-L1 assessment has become standard of care since use of frontline pembrolizumab in patients with advanced NSCLC is based on tumor PD-L1 expression. Other biomarkers are being actively evaluated to identify the patients most likely to benefit from these agents. Unique adverse effects are observed with the use of immune checkpoint inhibitors. Knowledge of the adverse effects and their management is crucial in treating patients with lung cancer using immune checkpoint inhibitors.

8557 Background: SCLC rapidly recurs after first-line platinum therapy, and while several agents are approved in the relapsed/refractory setting, there is no approved agent or existing standard of care for third-line in Japan. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting Delta-like 3 protein (DLL3), an atypical Notch ligand that is highly expressed in SCLC but not in normal tissue. This was the first study evaluating safety, PK, and preliminary anti-tumor activity of Rova-T in Japanese pts. Methods: This was an open label Phase 1, 3+3 dose-escalation study of Rova-T in Japanese pts with advanced recurrent SCLC (NCT03086239). Eligibility: progressive disease after ≥2 prior systemic regimens incl. ≥1 platinum-based regimen; ECOG 0-1. Pts received 0.2 or 0.3 mg/kg Rova-T IV on Day 1 of a 6-week cycle for 2 cycles. Objective was to evaluate safety, tolerability, PK, and preliminary efficacy and expression of DLL3. Antitumor activity was measured by RECISTv1.1, and DOR, PFS, OS were evaluated. Results: 29 pts were treated with Rova-T (6 at 0.2mg/kg, 23 at 0.3 mg/kg). Median age 68 yrs; 76% male; 64% DLL3 high (≥75% expression); 86% DLL3 positive (≥25%). 20 pts (69%) had received ≥3 prior lines of therapy. Similar PK and AEs were seen compared to previous studies in non-Japanese pts. The most frequently reported study drug-related AEs were platelet count decreased, pleural effusion, oedema peripheral, and aspartate aminotransferase increased, the majority Grade 1/2. No DLTs occurred, and both dose levels were tolerated. Three pts previously treated with ≥3 prior lines of therapy had confirmed partial response by investigator (10% of all pts; 17% of DLL3 high pts). For DLL3 high pts, mDOR was 3.0 mos (95% CI: 2.9, 4.1), mPFS was 2.9 mos (1.2-3.6), and mOS was 7.4 mos (4.1-11.9). Individual responses were analyzed in detail and radiographic data with tumor shrinkage will be shown. Conclusions: Rova-T demonstrated a manageable safety profile with promising preliminary efficacy in Japanese SCLC pts, in particular pts with DLL3 high expression. These data support further exploration of Rova-T treatment in Japanese pts with SCLC in global Phase 3 studies. Clinical trial information: NCT03086239.

8556 Background: Immune checkpoint blockade (ICB) is now a routine component of treatment in recurrent small cell lung cancer (SCLC). We evaluated the response to ICB in patients (pts) with recurrent SCLC and genomic features of response using next-generation sequencing (NGS). Methods: Pts with recurrent SCLC treated with ICB were identified. The majority of pts were treated outside of a clinical trial to focus emphasis on the real-world experience. Tumor mutation burden (TMB) and the landscape of somatic variants were determined by targeted NGS using MSK-IMPACT. Objective response rate (ORR) to ICB was determined using RECIST v1.1. PFS and OS were measured from the start of ICB and analyzed using Kaplan-Meier. Results: Between December 2013 and October 2018, 108 pts with SCLC were treated with ICB (57 subjected to NGS). Pts received PD-1 monotherapy alone (n = 28) or in combination with CTLA-4 blockade (n = 80). Median line of therapy was 2 (range 1-6). ORR was 14% (15/108, 95% CI 8-22%). From the start of ICB, median PFS was 1.4 months in non-responders and 10.8 months in responders (HR 0.2; 95% CI 0.13-0.32). Median OS was 6.3 months in non-responders and undefined in responders (range 8-44 months) (HR 0.26, 95% CI 0.16-0.44). Four responders remain on ICB treatment. TMB in the ICB-treated cohort was similar to that of an unselected cohort (n = 233) of SCLC (median 8.8 Mt/MB vs 8.2 Mt/MB, p = 0.71). Clinical benefit was enriched among those with a higher TMB (upper vs middle/lower tertile PFS HR 0.48, 95% CI 0.28-0.84, p = 0.01 and ORR 26% [5/19] vs ORR 8% [3/38]). Rates of whole genome duplication and commonly altered genes in SCLC ( TP53, RB1, KMT2C/D, NOTCH1/2/4, PTPRD, APC) were similarly distributed across responders and non-responders. Completion of whole-exome sequencing and PD-L1 testing is in progress. Conclusions: In pts with recurrent SCLC receiving routine clinical care, the ORR to ICB is comparable to reports from clinical trials. A high TMB was associated with a longer median PFS and better response. Further investigation into the genomic landscape of recurrent SCLC is needed to identify biomarkers predictive of response to ICB.

Small cell lung cancer remains one of the more frustrating malignancies for oncologists to treat. Although responses to initial platinum-based chemotherapy are high, most are not durable, and many patients are candidates for further palliative chemotherapy. Therapeutic options include reinduction or single-agent chemotherapy, depending on the duration of response to front-line treatment. Topotecan is the only approved agent for patients with relapsed disease. Several phase II studies have shown a modest benefit with other agents used today, although combination chemotherapy should be avoided because of increased toxicity. Palliative care should always be the focus, especially in patients with recurrent or chemorefractory small cell lung cancer and a poor performance status.

100Background: Patients (pts) with advanced (adv) SCLC after first-line platinum-based chemotherapy have limited options. Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, is approved for previously treated metastatic NSCLC in the US and for squamous NSCLC in the EU. Nivolumab + ipilimumab, a cytotoxic T-lymphocyte antigen-4 immune checkpoint inhibitor, has shown durable responses in multiple tumor types. CheckMate 032 was designed to evaluate nivolumab +/- ipilimumab in adv tumors including SCLC. Methods: AdvSCLC pts with progressive disease (PD) after ≥1 platinum-based chemotherapy, regardless of platinum sensitivity or tumor PD-1 ligand 1 (PD-L1) expression, were eligible. Pts received nivolumab ([mg/kg] N3 Q2W) or nivolumab + ipilimumab combination (N1 + I3 or N3 + I1 Q3W for 4 cycles then N3 Q2W). Primary endpoint was objective response rate (ORR). Additional endpoints were safety, overall survival (OS), progression-free survival (PFS), and biomarkers. Results: 180 pts were enrolled...

Aim: To evaluate efficacy and tolerability of topotecan treatment for recurrent small cell lung carcinoma. Patients and Methods: A total of 62 patients were evaluated retrospectively. Statistical analysis was performed using GraphPad Instat (version 3.05). Results: DFifty five of patients (89%) were male and 7 (11%) were female. Median age was 56.7 +/- 9.3 (34-75). Forty eight of patients (80%) were extensive stage (ES) at the time of diagnosis. Fifty of the patients (80.6 Medical Oncology Clinic) were given median 5.36 cycles of cisplatin-etoposide (2-8 cycles). Time to recurrence was 15.6 +/- 6.13 weeks in patients with limited stage (LS) and 6.3 +/- 3.82 weeks in extensive stage (ES) (p

Meeting abstracts Treatment options for SCLC after failing platinum-based (PLT) chemotherapy (CT) are limited. Combined blockade of programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) immune checkpoint pathways has anti-tumor activity with a manageable safety profile. Nivolumab

7503 Background: Patients (pts) with SCLC respond to initial platinum (PLT) based chemotherapy (CT), but rapidly progress. Combined blockade of PD-1 and CTLA-4 immune checkpoint pathways has anti-tumor activity with a manageable safety profile. Nivolumab (NIVO) is a fully human IgG4 PD-1 immune checkpoint inhibitor approved in the US & Japan. Interim safety and efficacy of NIVO +\- ipilimumab (IPI), a CTLA-4 checkpoint inhibitor, in pretreated SCLC pts are reported. Methods: Pts who were PLT sensitive or refractory and had progressive disease were enrolled regardless of tumor PD-L1 status or number of prior CT regimens. This open-label study randomized pts to NIVO 3 mg/kg IV Q2W or NIVO+IPI (1 + 1 mg/kg, 1 + 3 mg/kg or 3 + 1 mg/kg) IV Q3W for 4 cycles followed by NIVO 3 mg/kg Q2W. Primary objective was overall response rate (ORR). Other objectives were safety, PFS, OS and biomarker analysis. Results: Seventy-five pts were enrolled (NIVO, n = 40; NIVO+IPI, n = 35); 59% had ≥ 2 prior regimens. Drug-related ...

Background. Small cell lung cancer (SCLC) carries a very poor prognosis, although recent advances in chemotherapy have produced some long-term survivors. Despite this, recurrences are common, and these patients require a high level of surveillance. Given that the female gender is a favorable prognostic factor in patients with SCLC and that more women are becoming lung cancer survivors, it is important to consider sites of metastasis that are restricted to women. Case. This is a presentation of a 42-year old previously diagnosed with SCLC who presented with an isolated recurrence of SCLC in the ovaries. This is a case report of an isolated recurrence of SCLC in the ovaries with a review of the literature. Conclusion. Although systemic relapses and recurrences often occur in these patients, isolated metastasis such as this can occur and should be considered in female patients with a history of small cell lung cancer.

Fourteen patients with small cell lung cancer (SCLC) previously treated with one or two chemotherapy regimens were entered in this study. 5-fluorouracil 370 mg/m 2 or 300 mg/m 2 was given with folinic acid 200 mg/m 2 by i.v. rapid infusion on days 1 through 5. Cycles were repeated every 28 days. There were no objective responses. One patient had stable disease for 47 weeks. The overall median survival duration was 23 weeks. Toxicity was comparable to that seen in other studies of 5-fluorouracil plus folinic acid

7597 Background: Patients with small-cell lung cancer (SCLC) that progress after first-line therapy have a dismal prognosis. Second-line chemotherapy is effective for some patients, but there is little evidence for third-line chemotherapy. The purpose of this study is to evaluate the efficacy of third-line chemotherapy and clarify prognostic factors for patients receiving it. Methods: Between November 2001 and October 2011, 202 of 648 patients who were consecutively diagnosed with SCLC at the National Cancer Center Hospital East received third-line chemotherapy. We performed multivariate Cox regression analysis to identify the prognostic factors of overall survival after third-line chemotherapy (OS). Results: At the start of third-line chemotherapy, median age was 66 years (range 38-83), male/ female: 168/34, ECOG performance status (PS) 0/1/2/3: 22/122/49/9, stage at diagnosis LD/ED: 88/114, response to second-line chemotherapy CR/PR/SD/PD: 3/95/56/48, and median progression free survival after second-li...

Nineteen eligible patients with recurrent small cell lung cancer were treated with a 120 hour continuous infusion of 6-thioquanine at a starting dose of 35 mg/m2/day. There were no responses in these 19 patients. Toxicity was acceptable with the primary toxicity being hematologic. Based on this trial, 6-thioquanine is not felt to have significant antitumor activity in this patient population.

19111 Background: Small cell lung cancer constitutes up to 15% of 170,000 new lung cancer cases diagnosed each year. Patients (pts) that experience recurrence after initial treatment have a very po...

18011 Background: Recurrent SCLC has a poor prognosis and is devoid of treatment options that improve overall survival. Irinotecan and paclitaxel are both active agents against SCLC, and have synergistic preclinical interactions. We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel for patients with recurrent SCLC. Methods: Patients with SCLC who relapsed following one prior chemotherapy regimen were eligible. Other pertinent inclusion criteria were: ECOG performance status 0–2, adequate bone marrow, hepatic and renal function and willingness to provide informed consent. Patients with untreated brain metastasis were excluded. Paclitaxel (75 mg/m2) and irinotecan (50 mg/m2) were administered on days 1 & 8 of every 3-week cycle. Treatment was continued until progression up to a maximum of 6 cycles or unacceptable toxicity. The primary endpoint was response rate. Toxicity was graded by CTC version 2.0. The simon two-stage design was utilized and the estimated sample size was 55 patients (stage I - 23 patients; stage 2 - 32 patients). The study has a 90% power to detect a response rate of 30%, with an alpha error rate of 10%. Results: 55 patients have been enrolled and complete data are available for 32 patients at the time of this report. Patient baseline characteristics are: male 53%, PS 0–44%; PS 1–47% and PS 2–6%. The median age is 61 years. Fifteen patients received ≥ 4 cycles. Salient grades 3–5 toxicities seen: neutropenia (13%), fatigue (13%); diarrhea (3%), hypersensitivity (3%) and hyponatremia (3%).The objective response rate is 37% (95% CI 19%-55%) with 9 PRs and 1 CR. Additional 8 patients (24%) had stable disease. The median survival is 19.6 weeks (95% CI 15.1–29.4) and the 1-year survival rate is 15%. Conclusions: The combination of irinotecan and paclitaxel is well tolerated and has promising anti-cancer activity in recurrent SCLC. Updated data on all 55 patients will be available at the time of the presentation. No significant financial relationships to disclose.

TO THE EDITOR: Your recent case by Yamagishi and Watanabe (1) on obstructive jaundice as a presenting symptom of recurrent small cell lung cancer is interesting. The authors, however, claimed that there are no other reports in the literature that have demonstrated similar findings. This claim is not true. A review of the literature (Table 1) clearly reveals that there are a number of similar reports (2, 3, 4, 5, 6, 7). The report by Martin-Parra et al. (6), in particular, provides findings very similar to those reported by Yamagishi and Watanabe (1). This report was published in Spanish and the abstract in English, approximately 3 yr earlier. The authors referred in their letter to the cases reported by Johnson et al.(7); however, they did not mention any of the other five references. It is important that claims for first publication be approved by the editorial board of the The American Journal of Gastroenterology after careful review of the literature. If there are similar cases to that reported, yet there are educational values behind the case, the authors may need to provide a summary table comparing their findings with those already published.