Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer.

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 those in 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<0.001). In the overall population, 89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33). Overall survival data were immature; 29 patients died (9 in the osimertinib group and 20 in the placebo group). No new safety concerns were noted. CONCLUSIONS: In patients with stage IB to IIIA EGFR mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).

Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer.

PURPOSE: The phase 3 HERITAGE trial demonstrated that the biosimilar trastuzumab-dkst is well tolerated with similar efficacy (measured by overall response rate [ORR] and progression-free survival [PFS]) compared with originator trastuzumab combined with taxane followed by monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Herein, we present final overall survival (OS) from HERITAGE. METHODS: HERITAGE is a multicenter, double-blind, randomized, parallel-group study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab plus taxane followed by continued monotherapy until disease progression. Overall survival was to be assessed at 36 months or after 240 deaths, whichever occurred first, as observed from time of randomization of last patient. RESULTS: At the final analysis (36 months), 242 patients in the intention-to-treat population had died during the study: 116 and 124 in the trastuzumab-dkst and trastuzumab groups, respectively, and 1 untreated patient from each treatment group. Median OS by Kaplan-Meier analysis was 35.0 months with trastuzumab-dkst and 30.2 months with trastuzumab. Evaluation of PFS showed a median of 11.1 months in both treatment groups. No new safety concerns were reported from week 48 until the end of the survival follow-up. CONCLUSION: This is the first phase 3 trial of a trastuzumab biosimilar to report long-term survival data similar to originator trastuzumab in patients with MBC. The comparable long-term OS between the trastuzumab-dkst and originator trastuzumab groups further supports the similarity of trastuzumab-dkst with originator trastuzumab and establishes trastuzumab-dkst as a safe and effective treatment option for patients with HER2-positive MBC. ClinicalTrials.gov NCT02472964; 6/16/2015.

A plain language summary of results from the ADAURA study: osimertinib after surgery for patients who have early-stage EGFR-mutated non-small cell lung cancer.

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.

Randomized, double-blind, placebo-controlled study of aprepitant versus two dosages of olanzapine with ondansetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving high-emetogenic chemotherapy.

PURPOSE: We assessed the efficacy of aprepitant (APR) or 10 or 5 mg OLN (OLN10 or OLN5) plus ondansetron and dexamethasone for chemotherapy-induced nausea/vomiting (CINV) prophylaxis in patients receiving high-emetogenic chemotherapy (HEC). METHODS: Patients who received doxorubicin + cyclophosphamide or cisplatin were given intravenous ondansetron and dexamethasone prior to chemotherapy and oral dexamethasone on days 2-4 and randomized 1:1:1 to receive APR125 on day 1 and APR80 on days 2-3 or OLN10 or OLN5 on days 1-4. Matched placebo controls were used. The primary endpoint was no nausea in ≤ 120 h. Secondary endpoints included CINV severity, complete response (CR) rate, adverse effects (AE), and quality of life. RESULTS: Of 141 patients, 104 received AC and 37 received cisplatin. The no-nausea rates were 33% (APR), 43.2% (OLN10; p = 0.24), and 37% (OLN5; p = 0.87). Grades 2-4 nausea were experienced by fewer patients for OLN10 than for APR (24-120 h, 8.7% vs. 27.7%, respectively; p = 0.02; overall period, 19.6% vs. 40.4%, respectively; p = 0.03). The median visual analog scale nausea score from 24 to 120 h was significantly lower for OLN10 (2.3) than for APR (1.2, p = 0.03). The degrees of vomiting, CR, and AE were similar between the APR and OLN10 groups. CINV was similar between the OLN5 and APR groups. CONCLUSIONS: Nausea was less severe for OLN10 than for APR in patients receiving HEC, but other measures were similar. CINV prevention efficacy was comparable between OLN5 and APR.

Efficacy of ginger for prophylaxis of chemotherapy-induced nausea and vomiting in breast cancer patients receiving adriamycin-cyclophosphamide regimen: a randomized, double-blind, placebo-controlled, crossover study.

PURPOSE: The purpose of this study is to determine the efficacy of ginger for reducing chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients receiving adriamycin and cyclophosphamide (AC) regimens. METHODS: We enrolled breast cancer patients receiving AC who experienced moderate to severe nausea or vomiting during the first chemotherapy cycle. Subjects were randomized to receive a 500-mg ginger capsule or placebo twice a day for 5 days starting on the first day of the second AC cycle and were switched to the other treatment in the third cycle. All participants also received ondansetron and dexamethasone for CINV prophylaxis. Nausea severity was recorded once a day during the first 5 days of each cycle. The primary outcome was reduction in nausea score. RESULTS: Thirty-four subjects (68 cycles of AC) were enrolled. Mean (range) maximum nausea score in the first AC cycle was 58 (40-90). Thirty-three subjects (97 %) received the same AC doses in the second as in the third cycle. Mean (±standard error) maximum nausea scores in patients receiving ginger and placebo were 35.36 (±4.43) and 32.17 (±3.71), respectively. The difference in mean maximum nausea scores was 3 (95 % confidence interval, -3 to 9; P = 0.3). There were no significant differences between ginger and placebo in terms of vomiting incidence and severity, rescue medication use, chemotherapy compliance, and adverse events. CONCLUSIONS: Ginger (500 mg) twice daily was safe, but conferred no additional benefit in terms of reducing nausea severity in breast cancer patients receiving AC and ondansetron and dexamethasone for CINV prophylaxis.

Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial.

Importance: Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. Objective: To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer. Design, Setting, and Participants: Multicenter, double-blind, randomized, parallel-group, phase 3 equivalence study in patients with metastatic breast cancer. From December 2012 to August 2015, 500 patients were randomized 1:1 to receive a proposed biosimilar or trastuzumab plus a taxane. Chemotherapy was administered for at least 24 weeks followed by antibody alone until unacceptable toxic effects or disease progression occurred. Interventions: Proposed biosimilar (n = 230) or trastuzumab (n = 228) with a taxane. Main Outcomes and Measures: The primary outcome was week 24 overall response rate (ORR) defined as complete or partial response. Equivalence boundaries were 0.81 to 1.24 with a 90% CI for ORR ratio (proposed biosimilar/trastuzumab) and -15% to 15% with a 95% CI for ORR difference. Secondary outcome measures included time to tumor progression, progression-free and overall survival at week 48, and adverse events. Results: Among 500 women randomized, the intention-to-treat population included 458 women (mean [SD] age, 53.6 [11.11] years) and the safety population included 493 women. The ORR was 69.6% (95% CI, 63.62%-75.51%) for the proposed biosimilar vs 64.0% (95% CI, 57.81%-70.26%) for trastuzumab. The ORR ratio (1.09; 90% CI, 0.974-1.211) and ORR difference (5.53; 95% CI, -3.08 to 14.04) were within the equivalence boundaries. At week 48, there was no statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor progression (41.3% vs 43.0%; -1.7%; 95% CI, -11.1% to 6.9%), progression-free survival (44.3% vs 44.7%; -0.4%; 95% CI, -9.4% to 8.7%), or overall survival (89.1% vs 85.1%; 4.0%; 95% CI, -2.1% to 10.3%). In the proposed biosimilar and trastuzumab groups, 239 (98.6%) and 233 (94.7%) had at least 1 adverse event, the most common including neutropenia (57.5% vs 53.3%), peripheral neuropathy (23.1% vs 24.8%), and diarrhea (20.6% vs 20.7%). Conclusions and Relevance: Among women with ERBB2-positive metastatic breast cancer receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess safety and long-term clinical outcome. Trial Registration: clinicaltrials.gov Identifier: NCT02472964; EudraCT Identifier: 2011-001965-42.

Favorable outcome of immunotherapy in a rare subtype of hepatocellular carcinoma: a case report and literature review.

Scirrhous hepatocellular carcinoma (S-HCC) represents an uncommon subtype of HCC. During radiological evaluation this unique subtype is frequently mistaken as cholangiocarcinoma, fibrolamellar HCC, or metastatic adenocarcinoma. Here, we present the case of a 50-year-old woman with a large hepatic mass. A triple-phase computed tomography of the liver revealed an arterial enhancing lesion without portovenous washout at hepatic segment 4a/8. The liver biopsy showed hepatocellular characteristics and was positive for Hep Par 1, CK7, CK19, Arginase 1 and CEA, indicating atypical S-HCC. This patient had achieved tumor control with combined treatment with atezolizumab plus bevacizumab and was then treated with lenvatinib after tumor progression. The patient died 15 months after the initial diagnosis.

Pituitary metastasis from renal cell carcinoma: a case report with literature review.

A 52-year-old man suffered from visual disturbance for 5 months. He then developed malaise, constipation and anorexia with significant weight loss. Physical examination showed noticeable signs of hypothyroidism, such as slurred speech, dry skin, macroglossia, myoedema and slow relaxation of ankle reflexes. In addition, eye exam showed abnormal visual acuity with left homonymous hemianopia. A large mass was found at right scapular region. Endocrinologic investigation results were compatible with secondary hypothyroidism with adrenal insufficiency. Subsequent CT brain revealed an enhancing mass at pituitary gland and also a mass at right occipital lobe with surrounding edema. CT of chest demonstrated multiple lung nodules, right scapular mass and incidentally revealed 8.7-cm hypervascular mass at left kidney. The final diagnosis was renal cell carcinoma with bone, lung, brain and pituitary metastasis. He received hormone replacement therapy as well as bisphosphonate and brain radiation. Following treatments, he was able to return to work with recovery of visual impairment. Pituitary metastasis is a rare condition. Our patient presented with symptoms of hypothyroidism which may mimic pituitary adenoma, but had other clues of malignancy such as significant weight loss and scapular mass. The most common cancers that occasionally metastasize to pituitary gland are breast and lung cancer. Previously, renal cell carcinoma with pituitary metastasis has been reported. Unlike ourpatient, most of these cases developed metachronous pituitary metastasis.

A phase II study of the combination of gemcitabine plus carboplatin as the neoadjuvant treatment in locally advanced breast cancer.

OBJECTIVE: Although anthracycline-based regimen is standard neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC), there is some concern over its toxicities such as alopecia and cardiotoxicity. Gemcitabine is another active agent in metastatic breast cancer after failure to anthracycline with less toxicity. The objective of the present study is to evaluate the efficacy and safety of the combination of gemcitabine and carboplatin as NAC in LABC. MATERIAL AND METHOD: Patients with histologically confirmed LABC (T3, T4 or N2 and M0) were included. Patients were scheduled to receive 3 cycles of neoadjuvant GC (gemcitabine 1,000 mg/m2 D1, D8 and carboplatin AUC x 5 D1) every 21 days. Patients with clinical response underwent surgery and additional 3 cycles of adjuvant GC. Primary endpoint was clinical response rate whereas secondary endpoints included pathological response, DFS, OS and toxicity. RESULTS: Between 2004 and 2007, 40 LABC patients were enrolled. Of 40 patients, 35 were evaluable for efficacy and 40 for toxicity. Twenty-three out of 35 patients (65%) obtained cPR. Among 22 patients who had clinical response and who underwent surgery, overall pathological response rate was 51.5% with 1-pCR (2.9%) and 17-pPR (48.5%). All 7 triple-negative patients had pathological response (1-pCR, 6-pPR). At median follow-up of 59 months, median DFS and OS were not reached. Five-year OS and DFS were 67% and 62%, respectively Major adverse effect was myelosuppression without fatal complications. CONCLUSION: The combination GC was feasible and well-tolerated for LABC in neoadjuvant setting. Triple-negative subgroup seems to have high response to GC.

Cost-Utility and Budget Impact Analyses of Oral Chemotherapy for Stage III Colorectal Cancer: Real-World Evidence after Policy Implementation in Thailand.

This study conducted a cost-utility analysis and a budget impact analysis (BIA) of outpatient oral chemotherapy versus inpatient intravenous chemotherapy for stage III colorectal cancer (CRC) in Thailand. A Markov model was constructed to estimate the lifetime cost and health outcomes based on a societal perspective. Eight chemotherapy strategies were compared. Clinical and cost data on adjuvant chemotherapy were collected from the medical records of 1747 patients at Siriraj Hospital, Thailand. The cost-effectiveness results were interpreted against a Thai willingness-to-pay threshold of USD 5003/quality-adjusted life year (QALY) gained. A 5-year BIA was performed. Of the eight strategies, CAPOX then FOLFIRI yielded the highest life-year and QALY gains. Its total lifetime cost was also the highest. An incremental cost-effectiveness ratio of CAPOX then FOLFIRI compared to 5FU/LV then FOLFOX, a commonly used regimen USD was 4258 per QALY gained.The BIA showed that when generic drug prices were applied, 5-FU/LV then FOLFOX had the smallest budgetary impact (USD 9.1 million). CAPOX then FOLFIRI required an approximately three times higher budgetary level (USD 25.1 million). CAPOX then FOLFIRI is the best option. It is cost-effective compared with 5-FU/LV then FOLFOX. However, policymakers should consider the relatively high budgetary burden of the CAPOX then FOLFIRI regimen.

Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial.

PURPOSE: The phase III ADAURA (ClinicalTrials.gov identifier: NCT02511106) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non-small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30]; P < .001). We report an updated exploratory analysis of final DFS data. METHODS: Overall, 682 patients with stage IB-IIIA (American Joint Committee on Cancer/Union for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years. The primary end point was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test; following early reporting of statistical significance in DFS, no further formal statistical testing was planned. Secondary end points included DFS in stage IB-IIIA, overall survival, and safety. Patterns of recurrence and CNS DFS were prespecified exploratory end points. RESULTS: At data cutoff (April 11, 2022), in stage II-IIIA disease, median follow-up was 44.2 months (osimertinib) and 19.6 months (placebo); the DFS HR was 0.23 (95% CI, 0.18 to 0.30); 4-year DFS rate was 70% (osimertinib) and 29% (placebo). In the overall population, DFS HR was 0.27 (95% CI, 0.21 to 0.34); 4-year DFS rate was 73% (osimertinib) and 38% (placebo). Fewer patients treated with osimertinib had local/regional and distant recurrence versus placebo. CNS DFS HR in stage II-IIIA was 0.24 (95% CI, 0.14 to 0.42). The long-term safety profile of osimertinib was consistent with the primary analysis. CONCLUSION: These updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

Randomized, double-blinded, placebo-controlled trial of ondansetron plus dexamethasone with or without metoclopramide as antiemetic prophylaxis in patients receiving high-dose cisplatin in medical practice.

PURPOSES: Ondansetron plus dexamethasone are standard antiemetic agents for highly emetogenic chemotherapy. Metoclopramide is a dopamine antagonist, which may enhance efficacy of ondansetron and dexamethasone. The objective of this study was to assess the efficacy and tolerability of metoclopramide added to standard antiemetic regimen for prophylaxis of cisplatin-induced emesis. METHODS: Patients who received ≥50 mg/m(2) of cisplatin for the first time were given intravenous ondansetron and dexamethasone on day 1 and were randomized to receive either standard antiemetics (ondansetron 8 mg orally bid on days 2-5 and dexamethasone 8 mg orally bid on days 2-4) plus metoclopramide 20 mg orally qid on days 2-5 or a placebo. The primary endpoint was a complete response (CR) rate defined as no emesis and no rescue treatment over a 120-h period. Secondary endpoints included severity of nausea and vomiting, time to first emesis, quality of life, and adverse effects. RESULTS: Among 162 patients, 50 patients (60%) in the metoclopramide group and 42 patients (53%) in the control group achieved CR (p = 0.36). The mean times to first emesis in the metoclopramide and control groups were 88 and 75 h, respectively (p = 0.18). The degrees of nausea and vomiting in both groups were similar. Eleven patients (13%) in the metoclopramide group and 20 (25%) in the control group required rescue treatment (p = 0.05). Quality of life and adverse effects were not different between the two groups. CONCLUSION: The addition of metoclopramide to ondansetron plus dexamethasone reduced the use of rescue medication, but did not affect complete response rate, quality of life or adverse effects.

Clinical characteristics and disease outcome of UICC stages I-III colorectal cancer patients at Siriraj Hospital.

BACKGROUND: Colorectal cancer is the third most common cancer worldwide. There were only a few reports of disease outcomes in Thai. Therefore, the authors retrospectively reviewed the clinical characteristics and disease outcome of patients with curable colorectal cancer treated at Siriraj Hospital, the largest tertiary-care hospital in Thailand. MATERIAL AND METHOD: Medical records of colorectal cancer patients diagnosed at Siriraj Hospital between January 2003 and December 2007 were reviewed. The records of the patients presenting with stage I-III and had been follow-up for at least 2 years were explored. Clinical characteristics, including demographic data, primary tumor site, TMN staging, histopathology, and CEA level were described. Disease outcome including survival, recurrence of disease and complication were analyzed. RESULTS: One thousand forty-seven colorectal cancer patients were diagnosed and completely staged during the study period. The incidence of stage I-IV was 9%, 22%, 37% and 32%, respectively. Three hundred fifty-five patients with stage I-III colorectal cancer were analyzed. The ratio of male and female was 1.4:1. The median age was 59.8 years. Forty-eight percent and 52% of patients had colon and rectal cancer, respectively. The median follow-up time was 63.3 months. The mean time from diagnosis to surgery was 23 days. Two hundred forty eight patients (70%) received adjuvant or neoadjuvant chemotherapy with the majority receiving 5-fluorouracil and leucovorin. 5-year disease free survival rate in stage I-III was 90%, 85% and 58%, respectively and 5-year overall survival in stage I-III was 93%, 93% and 73%, respectively. Independent risk factors for disease-free survival were gender preoperative CEA and stage; for overall survival were gender and stage. CONCLUSION: Approximately two-thirds (68%) of patients with colorectal cancer at Siriraj hospital presented with a potentially curable stage. Multi-modality treatments with surgery, adjuvant chemotherapy and radiation resulted in comparable survival as in Western countries. Independent risk factors for worse survival in this cohort were stage III disease and male gender.

C-reactive protein as a monitor of chemotherapy response in advanced non-small cell lung cancer (CML study).

OBJECTIVE: The aim of the present prospective study was to evaluate the correlation between the change of serum c-reactive protein (CRP) levels and response to chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer. MATERIAL AND METHOD: Patients with locally advanced or metastatic non-small cell lung cancer who received the first line chemotherapy were measured serum CRP levels prior to treatment. Chemotherapy regimen was given to patients according to physicians and radiologic imaging was evaluated after two or three cycles of treatment. Serum CRP levels were measured first time at pre-treatment and second time in patients who had pre-treatment serum CRP levels greater than normal range (3 mg/l) at the time of response assessment or clinical progression. The primary endpoint was the correlation between change of serum CRP levels and radiologic response. The secondary endpoint was the prevalence of elevated CRP levels in advanced NSCLC patients and correlation between initial CRP levels and progression free survival (PFS). RESULTS: Fifty four patients were enrolled. Prevalence of elevated CRP levels in advanced NSCLC was 76%. Thirty patients had serial serum CRP measured. There was correlation between change in serum CRP levels and response to treatment (r = 0.43, p = 0.018, spearman rank). There was significant correlation between response to treatment and decrease in CRP levels greater than 50% (p = 0.009, Fisher's exact test). In contrast there was no correlation between progression and increase in CRP levels (p = 0.640, Fisher's exact test). All patients with serial CRP levels decreased to normal range (< 3 mg/ l) had response to chemotherapy. High pre-treatment CRP levels (> 100 mg/l) correlated with poor PFS. Median PFS for patients with pre-treatment CRP levels of 3-30 mg/l, 30-100 mg/l and >100 mg/l was 23.0 weeks, 13.0 weeks and 6.3 weeks, respectively. Patients with serial CRP levels less than 3 mg/l had greater PFS than patients with serial CRP levels higher than 3 mg/l (p = 0.026, log rank test). CONCLUSION: The present study suggested that high levels of pre-treatment serum CRP and persistent CRP in serum was a poor prognostic factor. The decrease in CRP levels greater than 50% was a simple method to predict the response to treatment in patients with locally advanced or metastatic non-small lung cancer.

Primary pulmonary lymphoepithelioma-like carcinoma treated with immunotherapy: A case report and literature review.

Here, we report a case of metastatic Epstein-Barr virus (EBV)-related primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) in a young, nonsmoking female who responded well to treatment with two types of immune checkpoint inhibitors (ICIs). This is the first case report of a favorable outcome to ICIs in the late-line treatment of advanced PPLELC patients with programmed cell death-ligand 1 (PD-L1) expression.

Loss of CDX-2 expression is an independent poor prognostic biomarker in patients with early-stage deficient mismatch repair colorectal cancer.

AIM: To investigate the clinicopathological factors, molecular features, and prognostic implications associated with loss of Caudal-related homeobox transcription factor 2 (CDX-2) expression in colorectal cancer (CRC) patients. METHODS: Immunohistochemistry for CDX-2 expression was performed on formalin-fixed, paraffin-embedded primary CRC tissue samples from 449 patients. Correlation between CDX-2 expression and clinicopathological and molecular characteristics was evaluated. Univariate and multivariate survival analyses were performed to determine the prognostic value of loss of CDX-2 expression. RESULTS: Of 449 patients, 84% were stage I-III. CDX-2-negative expression was identified in 18 of 441 (4.1%) patients. Loss of CDX-2 expression was more commonly found in patients with right-sided tumors rather than left-sided tumors (odds ratio [OR] = 3.57; p = 0.009), deficient mismatch repair (dMMR) compared to proficient MMR (pMMR) (OR = 3.7; p = 0.012), and BRAF mutation compared to BRAF wild type (OR = 8.06; p = 0.002). Univariate analysis revealed that stage I-III CRC patients with loss of CDX-2 expression had significantly worse overall survival (OS) and disease-free survival (DFS) than those with positive CDX-2 expression (5-year OS = 33.3% vs. 74.6%, respectively; p < 0.001, and 5-year DFS: 42.9% vs. 69.5%, respectively; p = 0.004). Loss of CDX-2 expression remained significantly associated with worse OS compared to positive CDX-2 expression in multivariate analysis (hazard ratio [HR] = 2.4; 95% confidence interval [CI], 1.12-5.11; p = 0.023). CONCLUSIONS: Loss of CDX-2 expression was found to be associated with right-sided tumor, dMMR status, and BRAF mutation. Moreover, loss of CDX-2 expression is a poor prognostic factor for OS in stage I-III, even among patients with dMMR tumors.

Low Fat-Free Mass Index Measured by Bioelectrical Impedance Analysis Correlates With Hematologic Adverse Events in Early-Stage Breast Cancer Patients Receiving Chemotherapy: A Prospective Observational Cohort Study.

Background: Low muscle mass is associated with worse cancer treatment outcomes. Although dual-energy X-ray absorptiometry or computerized tomography-based analysis have both been widely studied in this clinical setting, studies in the use of bioelectrical impedance analysis (BIA) remain limited. The aim of this prospective study was to investigate for association between body composition estimated by BIA and hematologic adverse events in early-stage breast cancer patients receiving chemotherapy. Methods: A total of 144 female patients were enrolled. Before the first cycle of chemotherapy, body weight and fat-free mass were measured by a BIA device and then those values were converted into body mass index and fat-free mass index. Association between fat-free mass index and composite adverse events (CAEs), including grade 4 neutropenia, febrile neutropenia, or relative dose intensity <85%, was explored. Results: CAEs occurred in 85 patients (59%), and point biserial correlation showed an inverse correlation between the fat-free mass index and CAE. No included patients were sarcopenic (fat-free mass index <11.4 kg/m2). Receiver operating characteristic curve analysis revealed <14.85 kg/m2 as the cutoff value indicating a low fat-free mass index. Using this cutoff, 85 patients were classified as having a low fat-free mass index, and 62 of those patients (72.9%) had CAE (relative risk: 1.86, P < .001). After adjusting for other factors, a low fat-free mass index was found to be independently associated with a high CAE (adjusted odds ratio: 4.562, 95% CI: 2.162-9.627, P < .001). Conclusion: Low fat-free mass index is an independent predictor of increased risk of hematologic adverse events in early-stage breast cancer patients receiving chemotherapy. Estimation of fat-free mass index by BIA may identify at-risk patients so that interventions can be considered to improve treatment outcomes.

Effect of Primary Tumor Location on Second- or Later-Line Treatment With Anti-Epidermal Growth Factor Receptor Antibodies in Patients With Metastatic Colorectal Cancer: A Retrospective Multi-Center Study.

BACKGROUND: Current guidelines recommend anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR Ab) as first-line treatment only in patients with left-sided RAS wild type (RASwt) metastatic colorectal cancer (mCRC). However, there are no guideline recommendations specific to tumor sidedness in subsequent-line treatment. This study aimed to investigate the effect of primary tumor location on second- or later-line treatment outcomes in patients with KRASwt mCRC. METHODS: Medical records of patients diagnosed with mCRC at 3 academic centers in Thailand (Siriraj, Chulalongkorn, and Ramathibodi hospital) between 2008 and 2019 were retrospectively reviewed. Patients with KRASwt mCRC who received anti-EGFR Ab in second- or later-line treatment were included. The impact of tumor sidedness on progression-free survival (PFS) was determined using Kaplan-Meier method, and those results were compared using log-rank test. RESULTS: Among the 2,102 patients who had KRAS analysis data, 1,130 (54%) patients had KRASwt. Of those, 413 patients received anti-EGFR Ab in second- or later-line treatment. One hundred and sixty-two of 413 (39%) patients had extended RAS analysis. Seventy (17%) patients had right-sided tumors. Two hundred and thirty-eight (58%) patients received anti-EGFR Ab in the third line, and 132 (32%) patients and 43 (10%) patients were treated in the second and more than third line, respectively. Single-agent irinotecan was the most commonly used backbone chemotherapy (303/413, 73%). Patients with right-sided tumors had non-significantly inferior PFS compared to patients with left-sided tumors (median PFS: 5.7 months (mo), 95% confidence interval [CI]: 3.9-7.5 vs. 7.5 mo, 95% CI 6.5-8.5; p=0.17). Subgroup analysis showed no difference in PFS when stratified by treatment lines. Patient with right-sided tumors had significantly inferior OS compared to patients with left-sided tumors (median OS: 23.3 mo vs. 29.9 mo; p=0.005). CONCLUSIONS: To date, this is the largest real world data of the effect of primary tumor location on anti-EGFR Ab which demonstrated that tumor sidedness has no significant impact on treatment outcomes in KRASwt mCRC patients receiving second- or later-line therapy. Our findings do not support the utility of tumor sidedness for treatment selection in these settings. We confirmed that patients with right-sided tumors had significantly worse survival.

Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial.

PURPOSE: In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful disease-free survival benefit in completely resected stage IB-IIIA EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA. PATIENTS AND METHODS: Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation. HRQoL (secondary endpoint) was measured using the Short Form-36 (SF-36) health survey at baseline, 12, and 24 weeks, then every 24 weeks until recurrence or treatment completion/discontinuation. Exploratory analyses of SF-36 score changes from baseline until week 96 and time to deterioration (TTD) were performed in the overall population (stage IB-IIIA; N = 682). Clinically meaningful changes were defined using the SF-36 manual. RESULTS: Baseline physical/mental component summary (PCS/MCS) scores were comparable between osimertinib and placebo (range, 46-47) and maintained to Week 96, with no clinically meaningful differences between arms; difference in adjusted least squares (LS) mean [95% confidence intervals (CI), -1.18 (-2.02 to -0.34) and -1.34 (-2.40 to -0.28), for PCS and MCS, respectively. There were no differences between arms for TTD of PCS and MCS; HR, 1.17 (95% CI, 0.82-1.67) and HR, 0.98 (95% CI, 0.70-1.39), respectively. CONCLUSIONS: HRQoL was maintained with adjuvant osimertinib in patients with stage IB-IIIA EGFRm NSCLC, who were disease-free after complete resection, with no clinically meaningful differences versus placebo, further supporting adjuvant osimertinib as a new treatment in this setting. See related commentary by Patil and Bunn, p. 2204.

Postoperative Chemotherapy Use and Outcomes From ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR-Mutated NSCLC.

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.