Platinum-based Chemoradiotherapy Research Articles

EP05.01-002 Real World Treatment Patterns and Outcomes among Unresectable Stage III Non-Small Cell Lung Cancer Patients Initiating Chemoradiotherapy

Concurrent platinum-based chemoradiation therapy (cCRT) with or without durvalumab consolidation for 12 months is the current standard of care for patients with unresectable stage III Non-Small Cell Lung Cancer (NSCLC). This study characterized the real-world treatment utilization patterns and associated outcomes after approval of durvalumab for this indication.

Anlotinib plus chemoradiotherapy in the treatment for FIGO stage IB3 and IIB-IVA cervical cancer: A prospective single-arm, single-center, exploratory phase II trial (299)

<b>Objectives:</b> Cervical carcinoma is the fourth leading cause of cancer-related death among women worldwide. Previous randomized clinical trials showed a 30% to 50% decrease in risk of death in locally advanced cervical cancer (LACC) with the addition of concurrent platinum-based chemoradiotherapy when compared with radiotherapy alone. Mechanisms to account for improved efficacy are thought to include direct cytotoxicity, radiosensitization of tumor cells, and control of subclinical metastases. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Anlotinib synergizes with radiation and cisplatin, as shown in preclinical and clinical studies. This phase II study aims to evaluate the efficacy and safety of adding anlotinib to concurrent chemoradiotherapy in FIGO stage IB3 and IIB-IVA cervical cancer. <b>Methods:</b> Inclusion criteria include treatment-naive histologically confirmed FIGO stage IB3 to IVA cervical cancer with at least one measurable lesion and ECOG performance score 0-2 within the age range of 18 to 75 years. Abundant organ functions are required, with no contraindication to anlotinib or chemoradiation present. Patients will be treated with oral anlotinib (12 mg qd, d1-14; 21 days per cycle; total 3 cycles) and X-ray external-beam radiotherapy (total 45Gy-50Gy in 25-28 fraction), followed by brachytherapy (6Gy/5 fractions or 7Gy/4 fractions) with concurrent cisplatin (40 mg/m2 weekly for 5-6 weeks). The primary endpoint is the progression-free survival (PFS) rate at three years. The secondary endpoints include overall response rate (ORR), disease control rate (DCR), overall survival (OS), and quality of Life (QOL). Safety will be evaluated in all patients who receive study drugs according to the treatment received (safety population) by recording clinical adverse events (AEs) using National Cancer Institute Common. The sample size calculation of 47 patients provides 80% power to detect a difference in survival at the two-sided 5% significance level using the log-rank test; considering a 10% reduction, a total of 53 samples are required. This study is currently open, and 23 patients have been enrolled. The estimated primary completion date is December 1, 2024, and the estimated study completion date is October 31, 2025.

Induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis.

BackgroundAdding induction chemotherapy to concurrent platinum-based chemoradiotherapy has significantly prolonged the survival time of patients with locoregionally advanced nasopharyngeal carcinoma. In this study, we intend to evaluate the survival outcomes, responses, and incidences of toxicities of induction chemotherapy and the differences between different strategies.MethodsA comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane CENTRAL on August 10, 2021. Single-arm or multi-arm prospective clinical trials on induction chemotherapy without targeted therapies or immune checkpoint inhibitors were included. Primary outcomes included survival outcomes, objective response rate, and disease control rate, and the secondary outcome was the rates of grade 3 or higher treatment-related adverse events.ResultsThe 39 studies included in the systematic review and meta-analysis comprised 36 clinical trials and 5389 patients. The estimates for 3-year overall and fail-free survival rates were 87% and 77%. The estimates for 5-year rates of overall and fail-free survival were 81% and 73%. Gemcitabine plus platinum and docetaxel combined with 5-fluorouracil plus platinum strategies were associated with the highest rates of 3-year and 5-year overall survival. The objective response and disease control rates were 85% and 98% after the completion of induction chemotherapy. Neutropenia (27%) and nausea/vomiting (7%) were the most common grade 3 or higher treatment-related hematological and non-hematological adverse events during the induction phase.ConclusionsDifferent induction chemotherapeutic strategies appear to have varying effects and risks; a comprehensive summary of the survival outcomes, responses, and toxicities in clinical trials may provide a crucial guide for clinicians.

Toripalimab combined with concurrent platinum-based Chemoradiotherapy in patients with locally advanced cervical Cancer: an open-label, single-arm, phase II trial

BackgroundConcurrent chemoradiotherapy is currently the standard of care for patients with locally advanced cervical cancer. However, even with the application of modern radiotherapy techniques, a considerable number of patients still develop distant metastases. PD-L1 inhibitors show good efficacy in cervical cancer. This single-arm phase II study aims to explore the efficacy and tolerability of combining PD-L1 inhibitor with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer.Methods/designThe primary endpoint of the study was the objective response rate assessed according to RECIST v1.1 criteria. The inclusion criteria were previously untreated patients aged 18–75 years with stage III-IVA (FIGO 2018 staging system) locally advanced cervical cancer. During concurrent chemoradiotherapy and consolidation chemotherapy, the enrolled patients will receive toripalimab (240 mg) every 3 weeks. After consolidation chemotherapy, the enrolled patients will be treated with toripalimab (240 mg) once every 6 weeks until the whole treatment cycle reaches 1 year. Intensity modulated radiotherapy was used for external beam radiation, and high-dose rate brachytherapy was delivered under image-guidance. Weekly DDP (40 mg/m2) was given concurrently with radiotherapy while 6 cycles of consolidated chemotherapy (paclitaxel plus DDP) were given after radiotherapy every three weeks. Secondary objectives included safety and tolerability, toxicity profile, progression-free survival, and overall survival.DiscussionPD-L1 inhibitor has shown good efficacy in recurrent/metastatic cervical cancer. However, there is still a lack of evidence about its combination with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. The purpose of this study is to explore the efficacy and tolerance of this combination therapy, so as to lay the foundation for the future phase III randomized study.Trial registrationclinicaltrials.govNCT05084677. Retrospectively registered on Octorber 07, 2021.

Prospective evaluation of immunological, molecular-genetic, image-based and microbial analyses to characterize tumor response and control in patients with unresectable stage III NSCLC treated with concurrent chemoradiotherapy followed by consolidation therapy with durvalumab (PRECISION): protocol for a prospective longitudinal biomarker study.

BackgroundConcurrent platinum-based chemoradiotherapy (CRT) followed by durvalumab maintenance treatment represents the new standard of care in unresectable stage III non-small cell lung cancer (NSCLC). In this prospective hypothesis-generating single-center study, we aim to identify a framework of prognostic and predictive biomarkers by longitudinal characterization of tumor- and patient (host)-related parameters over all phases of multimodal treatment.MethodsThis study will enroll 40 patients (≥18 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2, with a diagnosis of PD-L1 positive (≥1%), inoperable stage III NSCLC) with an indication for CRT followed by maintenance treatment with durvalumab according to European Medicines Agency (EMA) approval. Comprehensive analysis will include peripheral blood cellular and humoral immunophenotyping and circulating tumor DNA as well as gut/saliva microbiota analyses. Additional morphological analysis with 18F-FDG-PET/computed tomography (CT) before, 6 weeks, 6 and 12 months after the end of CRT is included. Statistical analysis using multiple testing will be used to examine the impact of different parameters on progression-free survival (PFS) and overall survival (OS) as well as tumor response and response duration.DiscussionThis protocol describes the methodology of a comprehensive biomarker study in order to identify a framework of prognostic and predictive markers for unresectable stage III NSCLC in a real-world setting.Trial RegistrationClinicalTrials.gov identifier (NCT05027165), data registered on August 2021.

Cost-effectiveness analysis of durvalumab as a maintenance treatment for patients with locally advanced, unresectable, stage Ⅲ nsclc in china.

The aim of this study was to evaluate the cost-effectiveness of durvalumab compared with Best supportive care (BSC) after chemoradiotherapy in patients with stage III non-small cell lung cancer from healthcare system perspective in China. A dynamic state transition model was adopted to simulate life time, direct medical costs and QALYs. In the base case scenario, for patients with unresectable, stage Ⅲ non-small cell lung cancer whose disease has not progressed after platinum-based chemoradiation therapy, the treatment group would use durvalumab whereas the control group would use BSC. Clinical data and health utility were derived from the patient-level data of Asian ethnicity in the PACIFIC trial. Cost of drug acquisition, follow-up, medical service, inspection, terminal care and adverse event treatment were considered in this model. The cost of durvalumab was calculated based on retail prices and Patient Assistance Program. In the base case, the durvalumab group yielded an additional 2.60 LYs and 2.37QALYs (discounted), causing an additional cost of 0.459 million RMB and 0.109 million RMB without and with PAP, so the ICER was 193,898 RMB/QALY and 46,093.12 RMB/QALY respectively. This study demonstrated that durvalumab can improve the survival of patients with unresectable, stage Ⅲ non-small cell lung cancer whose disease has not progressed after platinum-based chemoradiation therapy and would be a cost-effective option compared with BSC at a willingness to pay (WTP) threshold of 212676 RMB (three times GDP per capita of China in 2019).

Abstract 5962: Real-world practice patterns and outcomes after platinum and immunotherapy in stage III vs IV non-small cell lung cancer (NSCLC)

Abstract Background: Treatment of patients with locally advanced lung cancer includes platinum-based chemoradiation followed by anti-PD-L1/PD-1 immunotherapy. Over half of patients receiving this treatment have disease progression and may be re-challenged with further platinum or immunotherapy, or instead be treated with an approved third line (3L) therapy similar to that for patients initially diagnosed with stage IV disease that progressed on platinum and immunotherapy. It is unknown whether treatment outcomes and prognosis in the stage III setting, particularly in patients with early disease progression, mirror the stage IV setting. The purpose of this study was to evaluate current real-world practice patterns and survival for patients with stage III vs IV disease previously treated with platinum and immunotherapy. Methods: The Flatiron NSCLC database was used to identify patients whose disease progressed after platinum chemotherapy and anti-PD-L1/PD-1 therapy, and to further classify them as 1) stage III early progressors (≤ 6 months) after sequential platinum and durvalumab, 2) stage III late progressors (&amp;gt; 6 months) after sequential platinum and durvalumab, and 3) stage IV progressors after concurrent or sequential platinum and anti-PD-L1/PD-1 therapy. The proportion of stage III patients receiving additional platinum or immunotherapy vs approved 3L therapy (docetaxel ± ramucirumab, pemetrexed, or gemcitabine) was then evaluated. A Cox proportional hazards model was used to compare median overall survival in the stage III groups and the stage IV group starting the next line of treatment after initial platinum and immunotherapy, and adjusting for ECOG performance status, smoking history, histology, PD-L1 status, age, sex, and race. Results: Patients identified as receiving their first-line therapy between December 2017 and November 2020 included 143 stage III early progressors, 120 stage III late progressors and 876 stage IV patients. After initial platinum and immunotherapy, 34% of stage III early progressors received platinum or immunotherapy and 12% received approved 3L therapy. 39% of stage III late progressors received platinum or immunotherapy and 15% received approved 3L therapy. Median overall survival for early vs late stage III progressors did not significantly differ (10.1 vs 14.3 months; HR 0.89; 95% CI: 0.53, 1.51; P=0.67). Survival in stage III patients was longer than that in stage IV patients (median 6.2 months) among both early progressors (HR, 0.60; 95% CI: 0.44, 0.82; P=0.002) and late progressors (HR, 0.51; 95% CI: 0.51, 0.34; P=0.001). Conclusions: Patients with stage III NSCLC that progressed on initial platinum and immunotherapy were more likely to be re-challenged with platinum or immunotherapy than to immediately proceed to 3L therapy. These patients also had longer survival than analogous stage IV patients, regardless of progression timing. Citation Format: Palak Kundu, Adam Gondos, Tomohiro Tanaka, Elaine Chun, Marcus Ballinger. Real-world practice patterns and outcomes after platinum and immunotherapy in stage III vs IV non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5962.

Mammary analog secretory carcinoma in adults: A systematic review.

e18076 Background: Mammary analog secretory carcinoma (MASC) is a rare malignant salivary gland tumor of the head and neck region that was first described by Skálová et al. in 2010. It histologically mimics breast secretory carcinoma and parotid acinic cell carcinoma, and characterized by ETV6-NTRK3 fusion gene. This review aims to investigate the clinicopathologic features, treatment, and outcomes of MASC in adults. Methods: PubMed search for MASC adults (18+ years) from data inception through 2021, pooled with a case from our institution. Kaplan-Meier analysis was used to plot survival curves. Results: Of the 254 included cases, female:male ratio 1.02:1 with a mean age at diagnosis (±SD, range) of 50.1 (±16.7, 18–86) years. In terms of location, 143 (56.3%) occurred in the parotid gland, 21 (8.3%) in the submandibular gland, 21 (8.3%) in the lip, 15 (5.9%) in the thyroid gland–all (100%) had a component of classical type papillary carcinoma, 15 (5.9%) were cutaneous, 13 (5.1%) in the buccal mucosa, 12 (4.7%) split between hard and soft palate, 4 (1.6%) in the nasal mucosa, 2 (0.8%) in the lung, and remaining 8 (3.1%) each in the conjunctiva, tongue, minor salivary gland, submaxillary gland, maxillary sinus, ethmoid sinus, upper esophagus, and mandible. Patients mostly presented with swelling or growing mass in 95.4% (out of which, 93.3% were painless), followed by a painful ulcer in 1.8%. Median tumor size was 1.9 cm (range 0.3cm–8.5cm). Median duration of symptoms at time of presentation was 12 (range 1-360) months. Tumors were T1 (49.7%), T2 (23.9%), T3 (20.3%), and T4 (6.1%), N0 (81.9%), N1 (10.7%), N2 (7.4%), M0 (97.4%), and M1 (2.6%). Most patients (70.7%) presented as early stage (I or II) which was associated with a high survival probability based on a log-rank test (p-value: 0.0007). All patients had surgical resection, mostly combined with neck dissection (ND) in11.4%, radiation (RT) in 7.8%, ND+RT in 4.7%, ND with platinum-based chemoradiation in 1.0%, and one case reported use of Crizotinib followed by Entrectinib with disease progression at 4.5 and 7 months, respectively. Among patients with reported outcomes, 92.2% were alive with a median follow-up of 26 (range 1-228) months, and 7.8% deceased with a median time-to-death of 29 (range 1-107) months. Eleven (4.3%) reported a high-grade MASC and 18.5% of patients lived for over five years after their diagnosis. Conclusions: Early stage was a notable predictor of higher survival probability in MASC patients. Its rarity, heterogeneity of clinical behaviors, and variable outcomes make it even more challenging. This review serves as real-world evidence to further our understanding of this rare entity and shed light on prospective clinical trial design.

Prognostic analysis of doublet agent concurrent chemoradiotherapy in locally advanced cervical cancer: A propensity score analysis.

e17514 Background: Platinum-based concurrent chemoradiotherapy (CCRT) is the current standard treatment for patients with locally advanced cervical cancer (LACC). Previous reports showed that doublet agent CCRT can provide better prognosis than single agent CCRT. However, several controversies surround the doublet agent regimen. This retrospective study compared the efficacy and safety of cisplatin and nedaplatin in doublet agent CCRT by propensity score (PS) matching. Methods: Information on patients with stage IIB-IIIC2 cervical cancer who received doublet agent CCRT from January 2015 to December 2020 were collected. The chemotherapy regimen was docetaxel (75mg/m2) combined with carboplatin (AUC = 4-5) / cisplatin (50–70mg/m2) / nedaplatin (50-75mg/m2) once every 3 weeks. All patients underwent external-beam radiotherapy with intensity-modulated radiotherapy at a dose of 45–50 Gy/25fx to the pelvis with or without involving the para-aortic region and 60 Gy/25fx to gross disease in the lymph nodes, and 2-dimensional intracavitary brachytherapy with dose of 30 Gy/5fx to point A. Patients were classified into the cisplatin group and nedaplatin group. Treatment outcomes were compared between the two groups after 1:1 ratio PS matching adjusted for age, BMI, FIGO stage, pathology, tumor diameter, differentiation, complication, and cycles of chemotherapy. Categorical variables were compared using the χ2 test or Fisher's exact test. Clinical outcomes were analyzed using the Kaplan–Meier method with log-rank test. Results: There are 295 patients enrolled, median age 55 years (32–73 years). The median follow-up time was 38 months (5–77 months). The median number of chemotherapy cycle is 4 (1–6 cycles). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 82.5% and 80.4%, respectively. After PS matching, there were 83 patients each in the nedaplatin group and cisplatin group. All background factors between the two groups were well-balanced. There was no significant difference between the cisplatin and nedaplatin groups in terms of objective response rate (97.6% and 98.8%, p = 0.212), 5-year OS rate (96.5 vs.69.8, p = 0.066), and PFS rate (90.8 vs.72.4, p = 0.166). Also, there was no significant difference between the cisplatin and nedaplatin groups in terms of hematological toxicity (36.1% vs. 28.9%, p = 0.408), nausea and vomiting (19.3% vs. 20.4, p = 0.874), radiation proctitis (25.3% vs. 14.5%, p = 0.535), and radiation proctitis (12% vs.9.6%, p = 0.212). Conclusions: Doublet agent concurrent chemoradiotherapy is feasible, safe, and shows high efficacy in LACC patients. Here, the cisplatin group and nedaplatin group have similar prognosis and side effects, suggesting that nedaplatin and cisplatin are equivalent and can be replaced with each other for concurrent doublet agent CCRT.

Durvalumab (durva) after chemoradiotherapy (CRT) in unresectable, stage III, EGFR mutation-positive (EGFRm) NSCLC: A post hoc subgroup analysis from PACIFIC.

8541 Background: Standard of care for patients (pts) with unresectable (UR) stage III NSCLC is the ‘PACIFIC regimen’, based on data from the phase 3 placebo (pbo)-controlled trial where consolidation durva following CRT improved overall survival (OS; hazard ratio [HR], 0.68 [95% CI, 0.53, 0.87]) and progression-free survival (PFS; HR, 0.52 [95% CI 0.42, 0.65]), in an all-comer population. However, the benefit of immunotherapy (IO) in pts with EGFRm stage III NSCLC is unclear. We report a post hoc exploratory efficacy and safety analysis from 35 pts with EGFRm NSCLC from the PACIFIC trial (NCT02125461). Methods: Pts with stage III UR-NSCLC, WHO performance status (PS) 0/1 and no progression after ≥2 cycles platinum-based concurrent CRT were randomized 2:1 (1–42 days post CRT) to receive durva (10mg/kg IV q2w for up to 1 year) or pbo, stratified by age, sex, and smoking history; enrollment was not restricted by oncogenic driver gene mutation status or PD-L1 expression. Primary endpoints: PFS (BICR; RECIST v1.1) and OS; key secondary endpoints: objective response rate (ORR) and safety. Treatment effects for the EGFRm subgroup were estimated using an unstratified Cox proportional hazard model; medians were estimated using the Kaplan–Meier method. Statistical analyses were exploratory. Data cut-off (DCO) for the EGFRm subgroup efficacy analysis was 11 January 2021. Results: Of 713 pts randomized, 35 had EGFRm NSCLC based on local testing (durva n = 24, pbo n = 11). In the EGFRm subgroup, more pts in the pbo vs durva arm were male (73% vs 54%), had stage IIIA disease (64% vs 46%), PS 0 (64% vs 54%) and received pre-CRT induction chemotherapy (36% vs 8%). More pts in the durva arm were Asian (63% vs 55%) and had PD-L1 on &lt; 25% tumor cells (67% vs 36%); median age was consistent across arms. At DCO, median duration of follow-up for survival was 42.7 months (range, 3.7–74.3 months) for all randomized pts in the subgroup. Median PFS was 11.2 months (95% CI 7.3, 20.7) with durva vs 10.9 months (95% CI 1.9, not evaluable [NE]) with pbo; HR 0.91 (95% CI 0.39, 2.13). Median OS was 46.8 months (95% CI 29.9, NE) with durva vs 43.0 months (95% CI 14.9, NE) with pbo; HR 1.02 (95% CI 0.39, 2.63). ORR was 26.1% (95% CI, 10.2, 48.4) and 18.2% (95% CI 2.3, 51.8) with durva and pbo, respectively. The safety profile for durva was consistent with the overall population. In the durva and pbo subgroup arms, radiation pneumonitis was reported in 42% vs 36% of pts, and pneumonitis was reported in 17% vs 18% of pts (1 grade 3, pbo arm), respectively. Conclusions: In this post hoc exploratory analysis of 35 pts, PFS and OS outcomes with durva were similar to pbo in the EGFRm population, with wide CIs. The benefit of IO in this population remains unclear. The ongoing LAURA study (NCT03521154) is investigating the efficacy and safety of maintenance osimertinib in pts with locally advanced EGFRm stage III UR-NSCLC with no progression after CRT. Clinical trial information: NCT02125461.

Effect of delayed consolidation durvalumab and timing of treatment on survival outcomes in patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT).

e18809 Background: Consolidation treatment with durvalumab following CRT is now standard of care for pts with unresectable stage III NSCLC. In PACIFIC, durvalumab was administered within 42 days of completing CRT. There has also been recent interest in whether the time-of-day immunotherapy is given impacts on outcomes. In practice, many pts experience delays to consolidation immunotherapy, and the timing of infusions is variable. We investigated the effect of treatment delays and time-of-treatment on survival outcomes in a real-world setting. Materials &amp; Methods: A retrospective observational study was conducted with patients treated with consolidation durvalumab following concurrent platinum-based CRT for unresectable stage III NSCLC in 6 centres across Sydney, Australia between January 2018 and September 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS) based on RECIST v1.1, from completion of radiotherapy. We collected treatment initiation and completion dates as well the administration time of durvalumab. In the time-of-treatment analysis, pts were stratified into median time of treatment either before or after 12.00pm. Survival was estimated using Kaplan-Meier and Cox-proportional hazard models. Results: 145 pts were included in the study. Median age was 67 years. 62.3% of pts were male, 84.9% were smokers, and 57.5% had adenocarcinoma. The median time between completion of CRT and commencement of durvalumab was 59 days (11-187 days). 71.2% (n = 102) of pts experienced a treatment delay. Over a median follow-up of 18.9 months, median PFS was 33.9 months in pts treated within 42 days of CRT and 25.6 months in pts treated beyond 42 days of CRT (HR 0.97; 95% CI 0.46-2.06; p = 0.815). Median OS was not reached in either group but no difference in OS was observed in the two cohorts (HR 1.07; 95% CI 0.39-2.96; p = 0.88). Median timing of treatment did not affect outcomes for either PFS (HR 1.07; 95% CI 0.50-1.71; p = 0.80) or OS (HR 1.01; 95% CI 0.44-2.31; p = 0.91). Conclusions: No difference in survival outcomes was seen between patients who had received durvalumab 42 days after CRT compared to within 42 days. The median timing of treatment did not appear to impact outcomes in our cohort.

Patterns of failure after salvage chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer: 20-year experience in a single institution in Japan

The purpose of the present study was to evaluate patterns of recurrence after salvage chemoradiotherapy (SCRT) for postoperative loco-regional recurrent esophageal cancer. We reviewed records for 114 patients with postoperative loco-regional recurrent esophageal cancer treated by platinum-based chemoradiotherapy between 2000 and 2020, and we evaluated the patterns of failure in patients who had recurrence again or who had been observed for 2years or more after SCRT at the last observation date. One hundred and three patients were enrolled in this study. The median observation period for survivors was 60months. Fifty-three patients died of esophageal cancer and nine patients died of other diseases. The 5-year overall survival rate, cause-specific survival rate and disease-control rate were 43.7%, 45.3% and 37.0%, respectively. Sixty-five patients had failure after SCRT. In those patients, 26 patients had only distant organ or non-regional lymph node metastases, 26 patients had only loco-regional failure, and 13 patients had both. Of those 65 patients, 64 patients showed failure within 42months after SCRT. Of 39 patients with loco-regional failure, failure in the irradiated field was observed in 28 patients. Of those 28 patients, 27 patients showed failure within 24months and the other patient showed failure at 26.5months. The patterns of failure after SCRT for patients with postoperative loco-regional recurrent esophageal cancer were shown. The patterns of failure suggest that follow-up for at least 4years after SCRT should be performed for those patients.

Radiotherapy and Immunotherapy: The Power of the Teamwork for the Treatment of NSCLC.

Immune checkpoint inhibitors (ICPi) targeting programmed cell death 1(PD-1)/programmed cell death ligand-1 (PD-L1) have revolutionized the treatment of patients with advanced non-small cell lung cancer (NSCLC). Despite impressive success, only a small proportion of patients benefit from PD1/PDL1 inhibitors. Radiotherapy (RT) can induce a systemic anti-tumor immune response on local and distant tumors. Some preclinical and clinical evidence showed a critical role of RT to overcome acquired resistance to immunotherapy. Currently, durvalumab consolidation represents the new standard treatment for unresectable stage III NSCLC patients whose tumors express PDL1 on ≥1% of tumor cells (TC), and whose disease has not progressed following platinum-based chemoradiotherapy (CRT). In this review, we focus on the synergic effect of RT with ICPi and the new role that different RT schedules can play in combination with immunotherapy for early-stage NSCLC.

Propensity Score Matched Study of Tri-Weekly vs. Weekly Platinum-Based Chemotherapy Concurrent with Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

Objective: To compare tumor control and toxicity between tri-weekly chemotherapy and weekly platinum-based chemotherapy in locally advanced cervical cancer using the propensity score matching method.Material and Methods: DESIGN: Retrospective cohort with propensity score matched population. SETTING: Four university hospitals. PARTICIPANTS: 781 advanced local cervical cancer patients. INTERVENTION: tri-weekly platinum-based chemoradiotherapy versus weekly chemoradiotherapy OUTCOMES: Overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), and toxicity, including hematological and renal toxicity.Results: Overall median follow-up time was 59.5 months. After the propensity score matching process was completed, 326 patients were analyzed (163 in each group). The five-year OS was 66% and 64% (p 0.630); five-year LRFS was 85% and 81% (p 0.209); five-year RRFS was 89% and 94% (p 0.307); and five-year DMFS was 75% and 79% (p 0.420) in the tri-weekly and weekly groups, respectively. The patients in the tri-weekly and the weekly group had grade 2-3 neutropenia (10.5% vs 2.5%). The other toxicities appeared to be similar in both groups in terms of white blood count, platelet and creatinine.Conclusion: There was a potential small benefit of local control (4%) and overall survival (2%) with the tri-weekly regimen but we could not demonstrate statistical significance. However, this came at the price of an increase of 7% to 8% in grade 2-3 neutropenia.

115P Concurrent versus sequential immune checkpoint inhibition in stage III NSCLC patients treated with chemoradiation

Maintenance treatment with durvalumab after completion of chemoradiotherapy (CRT) in PD-L1-positive patients with inoperable stage III NSCLC is the international standard therapy. Treatment intensification with concurrent immunotherapy is controversial discussed. In this prospective study, we evaluated the role of concurrent versus sequential immunotherapy in patients receiving platinum-based CRT for stage III NSCLC.

Efficacy of platinum agents for stage III non-small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study

BackgroundPlatinum-based chemoradiotherapy is the standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC). However, few studies have evaluated the efficacy of subsequent chemotherapy for relapsed NSCLC following platinum-based chemoradiotherapy. This study aimed to evaluate the efficacy of platinum-doublet chemotherapy as a second-line treatment for patients with unresectable stage III NSCLC.MethodsWe retrospectively evaluated patients with unresectable stage III NSCLC treated with cytotoxic chemotherapy following platinum-based chemoradiotherapy who were registered in a nationwide registry NSCLC database. Patients were divided into the platinum-doublet chemotherapy (platinum) group and single-agent chemotherapy (non-platinum) group based on the type of second-line chemotherapy.ResultsThe platinum group (n = 119) showed significantly better overall survival (OS) than the non-platinum group (n = 201) (median OS: 21.5 vs. 10.5 months, hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.40–0.73, p < 0.001). OS from the beginning of chemoradiotherapy was also significantly better in the platinum group than in the non-platinum group (median OS: 34.9 vs. 21.8 months, HR: 0.58, 95% CI: 0.43–0.79, p = 0.001). In the multivariate analysis, platinum-doublet chemotherapy as second-line therapy, female sex, clinical stage IIIA, and duration of ≥ 8.6 months from the beginning of first-line therapy to the beginning of second-line therapy were associated with significantly better OS.ConclusionPlatinum-doublet chemotherapy as a second-line therapy may prolong survival in unresectable stage III NSCLC patients following platinum-based chemoradiotherapy. Thus, re-administration of platinum agents may be a promising treatment for unresectable stage III NSCLC treated with platinum-based chemoradiotherapy.

Highlights from the 2021 ASCO and ESMO annual meetings on radiotherapy of head and neck cancer

At this year's annual meetings of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), several studies on radiotherapy of locally advanced head and neck cancer were presented. For the indication of definitive radiochemotherapy, particularly the administration of immune checkpoint inhibitors concomitant to radiotherapy was investigated. In the phaseIII GORTEC-REACH trial, combined inhibition of epidermal growth factor receptor (EGFR) and programmed death-ligand (PD-L1) concomitant to radiotherapy of locally advanced head and neck cancer was inferior to platinum-based chemoradiotherapy. However, this therapeutic approach may be more efficient than radiotherapy with simultaneous EGFR inhibition alone. The concept of the phaseII CheckRad-CD8 trial with induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy after appropriate patient selection also proved to be highly efficient. In initial phaseII trials, dose de-escalation of radiotherapy seems feasible for HPV-positive oropharyngeal cancer after appropriate patient selection both postoperatively (ECOG-ACRIN E3311 trial) and after induction therapy (OptimaII trial). However, dose de-escalation should currently not be performed outside of clinical trials. In addition, first studies indicate abenefit of functional imaging (diffusion-weighted magnetic resonance imaging [MRI] or F‑fluoromisonidazole positron-emission tomography [FMISO-PET]) to establish personalized dose concepts in radiotherapy.

Final results of the IFCT-0803 study, a phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non-squamous, non-small-cell lung cancer

PurposeRoughly 20% of patients with non-small-cell lung cancer exhibit locally advanced, unresectable, stage III disease. Concurrent platinum-based chemoradiotherapy is the backbone treatment, which is followed by maintenance immunotherapy, yet with poor long-term prognosis. This phase II trial (IFCT-0803) sought to evaluate whether adding cetuximab to cisplatin and pemetrexed chemoradiotherapy would improve its efficacy in these patients. Materials and methodsEligible patients received weekly cetuximab (loading dose 400mg/m2 day 1; subsequent weekly 250mg/m2 doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75mg/m2) and pemetrexed (500mg/m2), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66Gy started on day 22. Disease control rate at week 16 was the primary endpoint. ResultsOne hundred and six patients were included (99 eligible patients). Compliance exceeded 95% for day 1 of chemotherapy cycles 1 to 4, with 76% patients receiving the 12 planned cetuximab doses. Maximal grade 3 toxicity occurred in 63% patients, and maximal grade 4 in 9.6%. The primary endpoint involving the first 95 eligible patients comprised two (2.1%) complete responses, 57 (60.0%) partial responses, and 27 (28.4%) stable diseases. This 90.5% disease control rate (95% confidence interval [95% CI]: 84.6%–96.4%) was achieved at week 16. After median 63.0-month follow-up, one-year and two-year survival rates were 75.8% and 59.5%. Median overall survival was 35.8months (95% CI: 23.5–NR), and median progression-free survival 14.4months (95% CI: 11.2–18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%. ConclusionThese survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.

Single-center prospective study on the efficacy of nivolumab against platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma

Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

Efficacy and safety of definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma.

252 Background: The standard treatment for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is platinum-based definitive chemoradiotherapy (dCRT). Previous clinical trials have indicated a clinical complete response (cCR) rate of 11%-25% and median overall survival (OS) of 9-10 months. The cCR rate is strongly correlated with good prognosis, however the predictive factors have not been elucidated. Methods: In this multi-institutional retrospective study, we evaluated the efficacy and safety of dCRT in patients with unresectable locally advanced ESCC. “Unresectable” was defined as the primary lesion (T4b) invading adjacent structures such as the aorta, vertebral body, and trachea, or the regional and/or supraclavicular lymph nodes (LNT4b) invading unresectable adjacent structures. cCR was determined by both computed tomography and endoscopy based on the Response Evaluation Criteria in Solid Tumors (version 1.1) with modifications and Japanese Classification of Esophageal Cancer (11th edition), respectively. Results: A total of 175 patients who started dCRT between January 2013 to March 2020, were included in this study. The overall median age was 68 (31-86). A total of 95 (54%) patients had a performance status of 0. Of these, 124 (71%) patients had T4b and 81 (46%) had LNT4b. The clinically involved site were as follows: thoracic aorta (22%), tracheobronchial tree (73%), and others (14%). The median tumor length was 6 (2-22) cm. 56 (32%) patients were tube-fed owing to obstructive tumors. 165 (96%) patients completed at least one cycle of chemotherapy with 60 Gy of radiation. Further, 84 (48%) patients received consolidation chemotherapy following dCRT. The confirmed cCR rate was 24% (42/175). At a median follow-up interval of 20 months, the 2-year OS and progression-free survival (PFS) rates of cCR cases vs. non-cCR cases were 90% vs. 31% (log-rank p &lt; 0.001) and 59% vs. 2% (log-rank p &lt; 0.001), respectively. Multivariate analysis of the clinicopathological factors contributing to cCR revealed that a tumor length of≥6 cm (OR, 0.4; 95% CI, 0.2–0.9 p = 0.03) was the only a significant predictive factor. The primary adverse events of grade 3 or above were esophagitis (32%), pneumonitis (13%), fistula formation (10%), febrile neutropenia (9%), and dyspnea (6%). Among 22 patients who originally presented with fistula formation, fistula disappeared in 14 (64%), including 3 cCR cases. Two (1%) sudden deaths secondary to severe hemorrhage and suspected aortic fistula were observed during the treatment period. Conclusions: dCRT is feasible for patients with unresectable locally advanced ESCC. The cCR rate of dCRT is consistent with that reported in previous clinical trials, and favorable OS and PFS rates were observed in patients with cCR. Tumor length was observed to be a significant predictive factor of cCR. Research Sponsor: None.