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Introduction: Adjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA. Methods: Patients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB-IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage. Results: Overall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10-0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13-0.40), regardless of disease stage. Conclusions: These findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

BACKGROUND: Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown. METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of thosein the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P

Here, we summarize the initial results from the ADAURA clinical study looking at treatment with osimertinib in patients with a specific type of non-small cell lung cancer (also called NSCLC). Osimertinib (TAGRISSO®) is a medication used to treat a type of NSCLC with a change (mutation) in the EGFR gene, known as EGFR-mutated NSCLC. EGFR stands for ‘epidermal growth factor receptor’. It is a protein present on the surface of both healthy and cancer cells that can regulate how cells grow and divide. Sometimes, certain mutations in EGFR can result in the EGFR protein malfunctioning, which can lead to the formation of cancer, like EGFR-mutated NSCLC. Based on previous clinical studies, osimertinib is already approved for use in patients with EGFR-mutated NSCLC that has spread beyond the lung (metastatic disease). This medication works to stop, prevent, or slow the growth of EGFR-mutated NSCLC tumors, by specifically blocking the activity of EGFR. In the ADAURA clinical study, participants had resectable EGFR-mutated NSCLC, which means they had tumors that can be removed by surgery. Participants took either osimertinib or a placebo (a dummy drug with no active ingredient) after having their tumors removed by surgery. Post-surgery chemotherapy was allowed, but not compulsory (this was decided by the participant and their doctor). To date, the study has shown that osimertinib could be beneficial for patients with resectable EGFR-mutated NSCLC. Participants who took osimertinib have stayed cancer-free for longer than those who took the placebo, regardless of whether or not they received chemotherapy after surgery. Osimertinib treatment also reduced the risk of tumors spreading to the brain and spinal cord, otherwise known as the central nervous system (also called CNS). The side effects experienced by the participants taking osimertinib have been consistent with what we already know. Based on the results from ADAURA, osimertinib has been approved for the treatment of resectable EGFR-mutated NSCLC after tumor removal. The ADAURA study is still ongoing and more results are expected to be released in the future. ClinicalTrials.gov NCT number: NCT02511106 .

HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. Tumors from chemotherapy-naive patients were screened centrally by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients with EGFR and/or HER2neu expression or amplification were allocated to three strata based on EGFR/HER2neu status and were randomized to lapatinib (arm A) or placebo (arm B), with 6 cycles of ECF or ECX (investigator-selected). The primary endpoint was progression-free survival (PFS) in stratum 3. 29 of 72 screened patients were randomized to strata 1 (HER2neu+: by FISH and IHC, n = 6), 2 (HER2neu−: by FISH/+ by IHC, n = 5) and 3 (HER2neu−/EGFR+, n = 18), of which 28 patients were eligible (14 per arm). Enrollment was curtailed after announcement of the negative LOGiC trial results. Median PFS was 8.0 versus 5.9 months (HR = 0.86, 95% CI 0.37–1.99) in the per protocol population, and 8.0 versus 6.3 months (HR = 0.85, 95% CI 0.30–2.46) for stratum 3, in the lapatinib versus placebo arm respectively. Median OS was 13.8 versus 10.1 months, respectively (HR = 0.90, 95% CI 0.35–2.27). There were no safety concerns. Central EGFR and HER2neu stratification by IHC and FISH can be used for further pan-HER strategies. Lapatinib with ECF/X was well tolerated, but did not show clear activity in patients with metastatic GC.

Gastroesophageal (GE) cancers continue to be a significant cause of mortality globally. Despite therapeutic advances in oncology, the prognosis of advanced GE cancer remains exceedingly poor. Immunotherapy has caused a major paradigm shift in the field of oncology. Not all patients benefit from these agents and several studies are trying to identify predictive and prognostic biomarkers to better inform and guide treatment decisions. The potential role of immunotherapy in GE cancers is emerging. These cancer types are molecularly and immunologically heterogeneous, and this heterogeneity influences the tumor microenvironment posing a significant challenge to studying biomarkers of response to immunotherapy. Here in this article, we discuss the need for new therapeutic approaches in GE cancers, review the emerging data on the activity of checkpoint inhibitors and the role of biomarkers in this setting.

11 Background: In the phase 2 CheckMate 142 trial, nivolumab plus low-dose ipilimumab provided robust and durable clinical benefit and was well tolerated as first-line therapy for microsatellite instability-high/DNA mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) (Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up data will be presented. Methods: Patients with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received nivolumab 3 mg/kg every 2 weeks plus low-dose ipilimumab 1 mg/kg every 6 weeks until disease progression or discontinuation. The primary endpoint was investigator-assessed objective response rate (ORR). Results: For all 45 patients (median follow-up was 13.8 months), ORR was 60% (95% CI 44.3–74.3). Responses were consistent with the overall population across subgroups including age, Eastern Cooperative Oncology Group (ECOG) performance status, prior adjuvant/neoadjuvant therapy, and mutation status (Table). Seven patients (16%) had grade 3–4 treatment-related adverse events; 3 (7%) had any grade treatment-related adverse events leading to discontinuation. Updated response, survival, and safety data after a longer follow-up (median 19.9 months) will be presented. Conclusions: Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated. Evaluated subgroups had responses consistent with the overall population. Nivolumab plus low-dose ipilimumab may represent a new first-line treatment option for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]

3521 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI provided robust and durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up data will be presented. Methods: Patients with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg every 2 weeks + low-dose IPI 1 mg/kg every 6 weeks until disease progression or discontinuation. The primary endpoint was investigator-assessed objective response rate (ORR). Results: For all 45 patients (median follow-up was 13.8 months), ORR was 60% (95% CI 44.3–74.3). Responses were consistent with the overall population across subgroups including age, Eastern Cooperative Oncology Group (ECOG) performance status, prior adjuvant/neoadjuvant therapy, and mutation status (Table). Seven patients (16%) had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had any grade TRAEs leading to discontinuation. Updated response, survival, and safety data after a longer follow-up (median 19.9 months) will be presented. Conclusions: NIVO + low-dose IPI demonstrated robust and durable clinical benefit and was well tolerated. Evaluated subgroups had responses consistent with the overall population. NIVO + low-dose IPI may represent a new 1L treatment option for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]

635 Background: In the phase II CheckMate-142 trial, NIVO + low-dose IPI (1 mg/kg) provided meaningful clinical benefit in previously treated MSI-H/dMMR mCRC pts after a median follow-up of 13.4 mo. Here, we present long-term follow-up (median 25.4 mo) of these pts. Methods: Pts received NIVO 3 mg/kg + low-dose IPI Q3W (4 doses) followed by NIVO 3 mg/kg Q2W until disease progression. Primary endpoint was investigator (INV)-assessed objective response rate (ORR; RECIST v1.1). Results: Of 119 treated pts, 76% had ≥ 2 prior lines of therapy. ORR and disease control rates (DCR) were 58 and 81%, respectively (Table). Complete response (CR) rate increased with long-term follow-up from 3 (13.4 mo) to 6% (25.4 mo). Median duration of response (DOR) was not reached, with 68% of responses ongoing at data cutoff. At 24 mo, progression-free survival (PFS) and overall survival (OS) rates were 60 and 74%, respectively; OS rates were 96, 56, and 29% in pts with CR or partial response (PR), stable disease (SD), and progressive disease (PD), respectively. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 31% of pts; 10% (grade 3–4) and 13% (any grade) of pts had TRAEs leading to discontinuation. Conclusions: Long-term follow-up with NIVO + low-dose IPI provides durable clinical benefit with deepening of response and a manageable safety profile with no new safety signals, demonstrating long-term benefit of NIVO + low-dose IPI for previously treated pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]

There is a great need to better design clinical trials that could improve patient outcomes and expedite drug development timelines. An understanding of general principles of classical clinical trial design and a consideration of innovative approaches and the concept of precision medicine carry great significance in that regard. It is important to keep in mind both the advantages and the pitfalls of different approaches, to maintain scientific rigor, and to always put patients first while improving how we conduct clinical trials.

The majority of the chemotherapy agents in use today cause various infusion reactions, from mild flushing to life-threatening events. The frequency of the reported hypersensitivity reactions induced by cetuximab varies between 3% and 22%. It is recommended in the literature to stop the infusion and replace cetuximab with panitumumab in case of hypersensitivity reactions observed during the treatment of colon cancer. Tumor lysis syndrome (TLS) may occur in colorectal cancers with heavy tumor load. Tumor lysis syndrome may be life-threatening. In our patient with widespread bone and liver metastases, treatment continued with cetuximab as a combination therapy with irinotecan in spite of the hypersensitivity and TLS led to a complete treatment response. The complete response observed after 3 months through continued therapy in our patient may present an example supporting treatment with cetuximab in spite of severe reactions.

The Center for Medical Technology Policy and the Molecular Evidence Development Consortium gathered a diverse group of more than 50 stakeholders to develop consensus on a core set of data elements and values essential to understanding the clinical utility of molecularly targeted therapies in oncology.

WOS: 000397930400218 … Genekor The study was supported by a grant provided by Genekor.

The following on Barrett's esophagus (BE) and animal models contains commentaries on the factors of BE carcinogenesis; a duodenoesophageal reflux model; translation of targeted therapies for esophageal adenocarcinoma; and novel target regimens selected through a proteomics screen.

The following on the treatments of adenocarcinomas in Barrett's esophagus contains commentaries on endo mucosal resection; choice between other ablative therapies; the remaining genetic abnormalities following stepwise endoscopic mucosal resection and possible recurrences; the Fotelo-Fotesi PDT; the CT TNM classification of early stages of Barrett's carcinoma; the indications of lymphadenectomy in intramucosal cancer; the differences in lymph node yield in transthoracic versus transhiatal dissection; video-assisted lymphadenectomy; and the importance of the length of proximal esophageal resectipon; and indications of sentinel node dissection.

Lesson Learned Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma. Background Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second-line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second-line therapy for advanced EAC. Methods The primary endpoint was response rate (RR). Patients with one prior treatment were given Pa 9 mg/m2 on day 1 and Ir 125 mg/m2 on days 1 and 8 of each 21-day cycle. Inclusion criteria were confirmed EAC, measurable disease, no prior Ir or Pa, performance status Results Twenty-four patients were enrolled; 18 were eligible and evaluable. These patients were all white, with a median age of 62.5 years (range, 33–79 years), and included 15 men and 3 women. The median number of cycles was 3.5. The most common grade 1–2 adverse events were fatigue, diarrhea, anemia, leukopenia, and hypoalbuminemia. Grade 3–4 adverse events included hematologic, gastrointestinal, electrolyte, rash, fatigue, and weight loss. The median follow-up was 7.2 months (range, 2.3–14 months). There were no complete remissions. The partial response rate was 6% (1/18; 95% confidence interval [CI], 0.01–0.26). The clinical benefit (partial response [PR] plus stable disease [SD]) rate was 50%. The median overall survival was 7.2 months (95% CI, 4.1–8.9) with an 11.1% 1-year survival rate. The median progression-free survival was 2.9 months (95% CI, 1.6–5.3). Conclusion Irinotecan and panitumumab as second-line treatment for advanced EAC are not active.

WOS: 000453611000008, PubMed ID: 27081583, Introduction: Breast cancer is the most common malignancy among Turkish women and the rate of early stage disease is increasing. The Oncotype DX (R) 21-gene assay is predictive of distant recurrence in ER-positive, HER2-negative early breast cancer. We aimed to evaluate the impact of the Recurrence Score (R) (RS) on treatment decisions and physician perceptions in Turkey. We also studied correlations between RS and routine risk factors. Patients and Methods: Ten academic centers across Turkey participated in this prospective trial. Consecutive breast cancer patients with pT1-3, pN0-N1mic, ER-positive, and HER2-negative tumors were identified at multidisciplinary tumor conferences. The initial treatment decision was recorded before tumor blocks were sent to the central laboratory. Each case was brought back to tumor conference after receiving the RS result. Both pre- and post-RS treatment decisions and physician perceptions were recorded on questionnaire forms. Correlations between RS and classical risk factors were evaluated using univariate and multivariate analyses. Results: Ten centers enrolled a total of 165 patients. The median tumor size was 2 cm. Of 165 patients, 57% had low RS, 35% had intermediate RS, and 8% had high RS, respectively. The overall rate of change in treatment decision was 33%. Initially, chemotherapy followed by hormonal therapy (CT+HT) was recommended to 92 (56%) of all patients, which decreased to 61 (37%) patients post-RS assay (p

Parakordoma, lokal rekurrens sıklığı fazla olan bir yumuşak doku tümörüdür. İndolen seyir izlemelerine rağmen nadir de olsa metastatik özellik gösterebilirler. Bu makalede beş yıl önce sağ omuzunda kitle nedeni ile opere edilen ve parakordoma tanısı olan 28 yaşında erkek hasta sunulmaktadır. Hastada ilk ameliyatından sonraki iki yıl içinde iki kez lokal nüks gelişmişti. Son olarak hasta metastatik sol retroorbital kitle ile başvurdu. Retroorbital kitleye parsiyel eksizyon yapıldı ve patolojik inceleme ilk tanısı ile uyumlu olarak myoepitelyal tümör metastazı şeklinde rapor edildi. Sistemik değerlendirmede multipl akciğer metastazı ve sağ sakroiliak eklemde metastaz tespit edildi. Sakroiliak ve retroorbital kitlelelere palyatif radyoterapi tamamlandıktan sonra kemoterapi başlandı. Kemoterapi rejimi ifosfamid, mesna ve doxorubisinden oluşmaktaydı. Kemoterapi sonrası değerlendirmelerde akciğer nodüllerinde ve retroorbital kitlede hafif regresyon görüldü. PET/BT’de sakroiliak metastazda 18-FDG tutulumu yoktu. Sonuç olarak, parakordomalar metastatik potansiyelleri nedeni ile yakın takip edilmelidir. Sistemik kemoterapide doksorubisin ve ifosfamid başarı ile kullanılabilir., Parachordoma is a soft tissue tumor with a high risk of local recurrence. Despite the fact that parachordomas mostly have an indolent course, distant metastasis can be seen on rare occasion. We hereby report a case of a 28-year-old male who was initially diagnosed with parachordoma five years ago when he presented with a mass on his right shoulder. He suffered from local recurrence twice within the first two years after his surgery. Metastatic disease later presented itself with a mass in his left retro-orbital fossa. The patient underwent a partial surgical resection and the pathologic evaluation was reported as ‘’myoepithelial tumor metastasis’’. The patient’s systemic work up showed bilateral pulmonary metastatic nodules and metastasis in the right sacroiliac joint. After radiotherapy for the sacroiliac and left orbital mass, chemotherapy was initiated. The regimen consisted of ifosfamide, mesna and doxorubicin. Follow-up evaluation revealed a minimal decrease in size in the pulmonary nodules and the retro-orbital mass. There was no 18-FDG uptake in the sacroiliac mass on PET-BT. In conclusion, surveillance carries importance due to the risk of metastasis for patients with parachordoma. Systemic chemotherapy consisting of doxorubicin and ifosfamide could be used successfully.

While pain is highly prevalent in cancer patients and its management is universally challenging, it is more commonly undertreated in the developing world. Southeastern European countries have limited resources and manpower to allocate for delivery of effective care for cancer-related pain. The purpose of this study was to explore the practice methods and the barriers to effective pain management in Southeastern Europe.We conducted a Web-based survey using a specially designed questionnaire among physicians practicing in member countries of the Balkan Union of Oncology (BUON).A representative from each of the member countries of BUON (including Armenia and Georgia) and close to 100 physicians from 8 countries responded. The majority (89%) of respondents were medical oncologists and had been practising for 10 years on average. For pain assessment, only 35.4% of the physicians used a formal pain scale. Of the respondents 34.1% were not able to reach the optimal doses of narcotic medications while managing cancer pain, mostly due to concerns about toxicity, such as constipation and nausea. Most physicians listed their inability to consult sub-specialists to seek assistance for improving pain management cases as one of the major difficulties in day-to- day clinical practice, along with lack of time.The limitations faced by our respondents seem to be related mostly to the shortcomings of the respective health care systems, along with the need for more experience and knowledge about the titration of pain medications and dealing with toxicities.

TPS4133Background: Approximately 10-20% of patients with gastric cancer (GCa) have HER-2 positive tumors. The addition of T to cisplatin/fluoropyrimidine-based CT improved survival in metastatic HE...

The following on the treatments of adenocarcinomas in Barrett's esophagus contains commentaries on endo mucosal resection; choice between other ablative therapies; the remaining genetic abnormalities following stepwise endoscopic mucosal resection and possible recurrences; the Fotelo-Fotesi PDT; the CT TNM classification of early stages of Barrett's carcinoma; the indications of lymphadenectomy in intramucosal cancer; the differences in lymph node yield in transthoracic versus transhiatal dissection; video-assisted lymphadenectomy; and the importance of the length of proximal esophageal resectipon; and indications of sentinel node dissection.

e11515 Background: The 21-gene Oncotype DX assay is accepted as an important predictive factor in the adjuvant treatment of node negative, estrogen receptor (ER) positive and HER2 (-) breast cancer...

e12536 Background: Approximately 5-10% of breast cancer cases are hereditary. Germline mutations in the BRCA1 and BRCA2genes are responsible for 80% of inherited breast cancer cases. Carriers of su...

49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) -- MAY 31-JUN 04, 2013 -- Chicago, IL, WOS: 000335419603613, …, Amer Soc Clin Oncol

e14602 Background: Survivin, also known as BIRC5, inhibits apoptosis by interfering with caspase activation. High expression of survivin is seen in fetal tissues and various cancers. Published lite...

4129 Background: EAC from BE is increasing and the prognosis is poor. The benefit from prevention of BE and EAC is great. The Sonic Hedgehog (Shh) pathway, a mediator of foregut development, may pl...

TPS206 Background: Esophageal carcinoma is highly lethal and the incidence is increasing, especially the subtype of EAC. Our group demonstrated that overexpression of the epidermal growth factor re...

IntroductionThe effect of neoadjuvant chemotherapy (NAC) on the expression of receptor status in locally advanced breast cancer (LABC) is still under investigation. Aims of this study are to evaluate changes in hormone receptor (HR) and HER-2 status post-NAC and correlation with survival.Materials and methodsLABC patients who received NAC between 2001 and 2008 at Istanbul University were analyzed retrospectively. Patients with pathologic complete response (pCR) were excluded in analysis. Immunohistochemical (IHC) analyses was performed on both initial biopsies and surgical specimens.ResultsThe median age of 128 patients was 48 years and 55% of them were premenopausal. Most of the patients had invasive ductal (81%) and histologic grade (HG) III (81%) breast cancer. Partial pathologic response (pPR) rate was 86.7%. HR status changed in 36 patients (28%). The rates of ER, PR and HER-2 receptor positivity at diagnosis and after NAC were 44–32.8%, 43–29.7%, and 24–21%, respectively. Negative-to-positive change in HR status was observed in five patients. The 5-year overall survival (OS) was 76% in patients whose HR status converted to negative, compared with 91% in patients who remained HR-positive (p