Outcome in patients of hormone receptor (HR) positive (Her 2) negative metastatic breast cancer treated with palbociclib – A real-world experience

Objectives: We present real-world outcome with the use of palbociclib in patients with HR-positive Her2-negative breast cancer treated at single center in India. Material and Methods: We conducted a medical audit of consecutive patients with HR-positive Her2-negative metastatic breast cancer, who were treated with palbociclib at our center between November 2016 and May 2020. Palbociclib was commenced at a dose of 125 mg orally once daily and a schedule of 21 days on therapy followed by 7 days off therapy was followed. Survival analysis included the Kaplan–Meier method using Statistical Package for the Social Sciences software (Version 26). HRs were calculated using Cox proportional hazard regression models and 95% confidence intervals (CIs) for the incidence estimates. Results: A total of 67 female patients were commenced on treatment with palbociclib between November 2016 and May 2020. The median age was 55 years (range 29–78 years). A total of 51 (76%) of these patients were postmenopausal and the remaining 16 were premenopausal. Baseline metastatic disease involved one organ/site in 23 (34%), two organs/sites in 32 (48%), three or more in 12 (18%). Bony metastasis alone was seen in 17 (25%) patients, visceral alone in 30 (45%), and the remaining 20 had both bony and visceral metastases. For these 67 patients, palbociclib was commenced as 1st line systemic therapy in 24 (36%) cases. Amongst the remaining 43 cases, it was 2nd line in 21 (31%); 3rd line and beyond in 22 (33%). Median PFS was 16.1 months (95% CI: 9.6–22.8) and median OS was 20.7 months (95% CI: 14.1–27.3). Median PFS for palbociclib use in first line was 18.7 months (95% CI: 4.6–32.9) while in subsequent lines, it was 13.8 months (95% CI: 9.8–17.9; log-rank P = 0.228). Median OS in patients who received palbociclib in first line was 23.2 months (95 % CI 20.1–26.3) and for those why received it in subsequent lines was 16.3 months (95 % CI: 12.5–20.1; P = 0.069). In total population, best response on imaging was CR in 11 (16%) cases (06 in 1st line setting and 05 in subsequent line setting); PR in 33 (49%); SD in 03; and progressive disease in 20. Median PFS with bone only metastasis: 20.9 months (95 % CI: 5.9–36.0), while with visceral metastasis 16.1 months (95% CI: 9.8–22.5; P = 0.537). Median OS with bone only metastasis: 22.7 months (95% CI: 17.8–27.5), while with visceral metastasis, it was 18.5 months (95% CI: 13.6–23.4; P = 0.314). Conclusion: Palbociclib is a useful addition in the management of HR +ve Her2 –ve breast cancer patients. Its benefit is confirmed in our real-world setting, both in the first and subsequent lines of therapy and the data are on similar lines as the global real-world data on palbociclib effectiveness.

A Retrospective Analysis of the Effect of Irinotecan-Based Regimens in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes

BackgroundAt present, patients with metastatic breast cancer (MBC) have few treatment options after receiving anthracyclines and taxanes. Studies have shown that irinotecan has modest systemic activity in some patients previously treated with anthracyclines and taxanes. This study aimed to evaluate the efficacy of irinotecan-based chemotherapy for breast cancer patients in a metastatic setting.MethodsWe retrospectively collected the clinical information and survival data of 51 patients with MBC who received irinotecan at West China Hospital of Sichuan University. The primary endpoints were the progression free survival (PFS) and overall survival (OS), and the secondary endpoint was the objective response rate (ORR). To minimize potential confounding factors, we matched 51 patients who received third-line chemotherapy without irinotecan through propensity score matching (PSM) based on age, hormone receptor (HR), and human epidermal growth factor receptor 2 (HER2), compared their OS and PFS rates to those treated with irinotecan.ResultsFrom July 2012 to October 2020, 51 patients were treated with an irinotecan-containing regimen. The median number of previous treatment lines was 4, and a median of two previous chemotherapy cycles (ranging from 1–14 cycles) were given in a salvage line setting. The ORR was 15.7%, and the disease control rate (DCR) was 37.3%. For the irinotecan group, the median PFS was 3.2 months (95% CI 2.7–3.7), while the median OS was 33.1 months (95% CI 27.9–38.3). Univariate analysis results suggested that irinotecan could improve PFS in patients with visceral metastasis (P=0.031), which was 0.7 months longer than patients without visceral metastasis (3.5 months vs. 2.8 months). Compared to the patients who received third-line non-irinotecan chemotherapy, the irinotecan group showed a longer trend of PFS without statistical significance (3.2 months vs 2.1 months, P = 0.052). Similarly, the OS of the irinotecan group was longer than the third-line survival without irinotecan, but it was not statistically significant (33.1 months vs 18.0 months, P = 0.072).ConclusionsFor MBC patients who were previously treated with anthracyclines and/or taxanes, an irinotecan-containing regimen achieved moderate objective response and showed a trend of survival benefit, which deserves further study.

Stratification of Prognoses based on Criteria from Clinical Trials of Metastatic Hormone-sensitive Prostate Cancer

Background: Oncologic outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) are extremely heterogeneous. We aimed to (1) stratify the prognosis in mHSPC patients according to criteria for high-volume disease, as defined in clinical trials, and (2) identify the combinations of unfavorable risk factors.Methods: This retrospective study reviewed 623 patients who were diagnosed with mHSPC between 1996 and 2014. The prognoses of mHSPC patients were stratified by criteria from the GETUG15, CHAARTED, STAMPEDE, and LATITUDE trials. The exclusion criteria were incomplete clinical data, docetaxel chemotherapy with upfront options, and metastatic disease without proper management after initial diagnosis.Results: All 485 patients (median follow-up=36.1 months) were categorized according to stage: M1a (70, 14.4%), M1b (367, 75.7%), and M1c (48, 9.9%). Significant differences in overall survival (OS) and cancer-specific survival (CSS) were found among the groups with low-volume disease, as classified by four clinical trials (log-rank p=0.001 and p<0.001, respectively). Bone metastasis volume and liver metastasis were independent predictors of prognosis. According to disease classification under NCCN guidelines, the prognosis of CSS between low-volume disease patients and M1c patients (no bone metastasis and low-volume bone metastasis) was not significantly different. Additionally, the prognosis of CSS did not significantly differ between M1c (high-volume bone metastasis and visceral metastasis, except liver) and M1b (high-volume bone metastasis) patients.Conclusions: The prognoses of patients with low-volume disease, based on several classification systems, were heterogeneous. Except for lung or liver metastasis, the combination of visceral metastasis with no/low-volume bone disease should be considered as a proxy of less aggressive disease in patients presenting with mHSPC.

Efficacy of Fulvestrant in Women with Hormone-Resistant Metastatic Breast Cancer (mBC): A Canadian Province Experience

Introduction: Fulvestrant has demonstrated efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC), both in first-and second-line settings. In clinical practice, however, fulvestrant has been used as a later-line therapy. This study assessed the efficacy of fulvestrant in women with mBC in early-versus later-line therapy. Methods: This retrospective cohort study assessed Saskatchewan women with HR+ mBC who received fulvestrant between 2003–2019. A multivariate Cox proportional survival analysis was performed. Results: One hundred and eighty-six women with a median age of 63.5 years were identified—178 (95.6%) had hormone-resistant mBC, 57.5% had visceral disease, and 43.0% had received chemotherapy before fulvestrant. 102 (54.8%) women received ≤2-line-therapy, and 84 (45.2%) received ≥3 line-therapy before fulvestrant. The median time to progression (TTP) was 12 months in the early-treatment vs. 6 months in the later-treatment group, p = 0.015. Overall survival (OS) from the start of fulvestrant was 26 months in the early-treatment group vs. 16 months in the later-treatment group, p = 0.067. On multivariate analysis, absence of visceral metastasis, HR: 0.70 (0.50–0.99), was significantly correlated with better TTP, whereas post-fulvestrant chemotherapy, HR: 0.32 (0.23–0.47), clinical benefit from fulvestrant, HR: 0.44 (0.30–0.65), and absence of visceral metastasis, HR: 0.70 (0.50–0.97), were correlated with better OS. Conclusions: Fulvestrant has demonstrated efficacy as both early-and later-line therapy in hormone-resistant mBC. Our results show that women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease, had better survival.

Prognostic factors in patients with advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy: a cohort study

Purpose Prognostic factors for the survival of patients with advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy remain controversial. The aim of this study was to identify the clinical factors that predict prognosis in patients with advanced HER2-positive gastric cancer. Methods We retrospectively reviewed the medical records of HER2-positive gastric cancer patients treated with trastuzumab-based chemotherapy at our institution. Clinical features and laboratory test results that considered prognostic factors were re-examined. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate analysis was performed with the log-rank test and multivariate analysis was performed using Cox’s proportional hazard regression model. Results A total of 133 patients with advanced HER2-positive gastric cancer were enrolled. The median OS in this cohort was 18.7 months. Four prognostic factors: visceral metastasis (lung or liver), levels of haemoglobin (Hb) (< 11.6 g/dL), lactate dehydrogenase (LDH) (> 222 mg/dL), and C-reactive protein (CRP) (> 0.14 mg/dl) were identified as independent prognostic factors. The patients were placed into three groups according to their number of prognostic factors. These included low (0,1), moderate (2,3), and high (4) risk factors. The OS was separated into three categories with a median OS of 32.0, 18.7 and 10.1 months respectively. Compared to the low-risk group, hazard ratios for the moderate- and high-risk groups were 1.75 and 3.49, respectively. Conclusion Visceral metastasis and abnormal Hb, LDH, and CRP levels were associated with unfavorable OS. These findings may be beneficial for the management of advanced HER2-positive gastric cancer treated with trastuzumab-based chemotherapy.

“Hurricane-like” Presentation of a Recurrent Marjolin's Ulcer in a Young Female

Marjolin’s ulcer (MU) with rapid progression and multiple distant metastases is rare. We report a case of an MU of the thigh developing in a postburn scar, which after successful R0 resection developed multiple bony and visceral metastasis to femur, vertebra, skull, lung, and liver within 3 months of excision. We highlight the “hurricane-like” recurrence in an MU, which is unusual for the metachronous disease. We stress that MUs, unlike conventional wisdom, need a thorough metastatic workup at presentation, and prognostication of a possible rapidly progressive course after surgery which may lead to grave prognosis and mortality.

Clinical Characteristics and Prognosis of Renal Cell Carcinoma With Spinal Bone Metastases

BackgroundThe prognosis of renal cell carcinoma (RCC) with spinal bone metastasis (sBM) varies greatly. In this study, we aimed to define the clinical characteristics and prognostic factors of RCC with spinal bone metastasis (sBM) in our center.MethodsThe clinical and medical records of RCC patients with sBMs were collected. The gender, age, time of BM, the extent of BM, the number of BMs, the presence or absence of visceral metastasis, and the pathological type of BM were investigated. All patients were followed up regularly. Overall survival (OS) was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan-Meier method and modelled with Cox regression analysis.ResultsForty-three RCC patients with sBM were collected. sBM was found synchronously in 30 patients (70%) and metachronously in 13 patients (30%). The median survival time was 30 months in 13 patients (30%) with solitary sBM and 19 months in 30 patients (70%) with multiple sBMs (P = 0.002). Visceral metastasis occurred in 12 patients (28%) with the median survival time of 17 months, while the other 31 patients (72%) had no visceral metastasis with the median survival time of 29 months (P&lt;0.001). En-block resection was done in 10 patients with median survival time of 40.1 months. Non-en-block resection were done in 33 patients with median survival time of 19.7 months (P&lt;0.001). Multivariate COX regression analysis showed that MSKCC score, number of BM, visceral metastasis, and en-block resection are the independent prognosis factors of RCC patients with sBM.ConclusionsMSKCC risk stratification, number of sBM, visceral metastasis and en-block resection are significant prognostic factors for OS in RCC patients with spinal BM. Therefore, for selected patients who has solitary spinal BM with no visceral metastasis, en-block resection of spinal BM can potentially prolong survival and is the treatment of choice.

Efficacy of Fulvestrant in Women with Hormone-Resistant Metastatic Breast Cancer (mBC): A Canadian Province Experience

Introduction: Fulvestrant has demonstrated efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC), both in first- and second-line settings. In clinical practice, however, fulvestrant has been used as a later-line therapy. The study aimed to assess the efficacy of fulvestrant in women with mBC in early- versus later-line therapy. Methods: In this retrospective cohort study, women with HR+ mBC who received fulvestrant between 2003–2019 in Saskatchewan were assessed. A multivariate Cox proportional survival analysis was performed. Results: 186 women with a median age of 63.5 years were identified; 178 (95.6%) had hormone resistant mBC, 57.5% had visceral disease, and 43.0% had received chemotherapy before fulvestrant. 102 (54.8%) women received ≤ 2-line-therapy, and 84 (45.2%) received ≥ 3 line-therapy before fulvestrant. The median time to progression (TTP) was 12 months in the early-treatment vs. 6 months in the later-treatment group, p = 0.015. Overall survival (OS) from the start of fulvestrant was 26 months in the early-treatment group vs. 16 months in the later-treatment group, p = 0.067. On multivariate analysis, absence of visceral metastasis, HR: 0.70 (0.50–0.99), was significantly correlated with better TTP, whereas post-fulvestrant chemotherapy, HR: 0.32 (0.23–0.47), clinical benefit from fulvestrant, HR: 0.44 (0.30–0.65) and absence of visceral metastasis, HR: 0.70 (0.50–0.97), were correlated with better OS. Conclusions: Fulvestrant has demonstrated efficacy as both early- and later-line therapy in hormone-resistant mBC. Women with clinical benefit from fulvestrant, who received post-fulvestrant chemotherapy, or had non-visceral disease had better survival.

An open-label, single-arm, multicenter, phase II study of RC48-ADC to evaluate the efficacy and safety of subjects with HER2 overexpressing locally advanced or metastatic urothelial cancer (RC48-C009).

4584 Background: There is still urgent medical needs in the patients with locally advanced or metastatic urothelial cancer (mUC) post to the failure of at least one line chemotherapy. RC48-ADC, a novel humanized anti-HER2 antibody-drug conjugate (ADC), has proved its efficacy in these patients (RC48-C005, NCT03507166), most of whom had received gemcitabine and platinum. Taking into consideration that taxane is another possible active agent for mUC, this study aims to further evaluate the efficacy of RC48-ADC in HER2 overexpressing mUC post to the failure of platinum, gemcitabine and taxane. Methods: This study was an open-label, multicenter, single-arm, non-randomized phase II study. Eligibility criteria included: histologically confirmed UC, HER2 overexpressing (IHC 2+ or 3+), ECOG PS 0-1, failed platinum, gemcitabine and taxane. The patients received RC48-ADC treatment alone (2 mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, death or study termination. The primary endpoint was objective response rate (ORR) assessed by blinded independent review committee (BIRC) according to RECIST v1.1. Progress-free survival (PFS), duration of response (DOR), overall survival (OS), and safety was also assessed. Results: Patient enrollment for this study started in December 2018 and completed in September 2020. A total of 64 patients were enrolled, with a median age of 62.5 years. At baseline, most patients (82.8%) had visceral metastasis. Fifty-five patients (85.9%) had received ≥ 2 lines treatment and 19 (29.7%) patients had prior immune checkpoint inhibitor (CPI) therapy. As of Nov 30, 2020, the confirmed ORR assessed by BIRC was 46.9% (95% CI: 34.3%, 59.8%) and the median DOR was 8.3 months (95% CI: 4.3, NE), the median PFS was 4.3 months (95% CI: 4.0, 6.8). The median OS was 14.8 months (95% CI: 8.7, 21.1). The ORR was 60.0% (15/25) in patients with HER2 IHC3+ or FISH test positive, 45.3% (24/53) in patients with visceral metastasis, 42.1% (8/19) in patients post to CPI therapy. The ORR was 55.6% (5/9), 50.0% (21/20) and 30.8% (4/13), in patients who had received 1 line, 2 lines and ≥ 3 lines treatment, respectively. Most commonly reported TRAEs were leukopenia (45.3%), AST increase (43.8%), neutropenia (42.2%), hypoesthesia (42.2%), ALT increase (37.5%) and fatigue (35.9%); Most commonly reported ≥ grade 3 TRAEs were neutropenia (9.4%) and hypoesthesia (6.3%) Conclusions: In patients with HER2 overexpressing (IHC 2+ or 3+) mUC who had failed platinum, gemcitabine and taxane, and the great majority of whom had received ≥2 prior lines treatment, RC48-ADC has demonstrated consistently excellent efficacy and benefit-risk profile compared with the RC48-C005 study which enrolled patients with mUC who had received ≥1 line prior chemotherapy. Clinical trial information: NCT03809013.

The clinicopathological characteristics, gene mutation characteristics and survival analysis of carcinoma of unknown primary origin.

e15098 Background: Analyze the characteristics of CUPS clinicopathology and gene mutation spectrum, and discuss CUPS drug treatment strategies. Methods: A retrospective analysis of the data of 30 patients with metastatic cancer of CUP admitted to our department from April 2015 to April 2020. Including clinicopathological characteristics, treatment process and methods, gene molecular information, follow-up survival period. The follow-up was until February 1, 2021 or the patient died. Results: The pathological types of these cases were adenocarcinoma (14/30,46.7%), squamous cell carcinoma (5/30, 16.7%), neuroendocrine carcinoma (3/30,10%), small cell carcinoma (2/30,6.7%), sarcomatoid carcinoma (2/30,6.7%), large cell carcinoma (1/30,3.3%), lymphoepithelial carcinoma (1/30,3.3%), and poorly differentiated carcinoma (2/30,6.7%) . The most predilection site was lymph nodes, accounting for 70%. Primary lesions were not found in 23 cases in the course of diagnosis and treatment. They were head and neck in 1 case, lung in 1 case, mammary gland in 1 case, digestive tract in 3 cases and thymus in 1 case. 23 patients received chemotherapy alone or combined with antiangiogenic therapy, 2 patients received molecular targeted agents, 1 patient received ICI combined with antiangiogenic therapy, and the remaining 4 patients died without antitumor therapy or gave up treatment. The survival time of 26 patients was between 1 to 143 months, and the median survival time was 8.6 months. The 1-year, 2-year, 3-year and 5-year OS rate were 40%, 20%, 6.7% and 3.3%, respectively. Mean survival time was significantly longer among patients without visceral metastasis vs. with visceral metastasis (15.6m vs. 7.3m, P = 0.023). OS rate were 70% vs. 25%, 30% vs. 15%, 20% vs. 0% and 10% vs. 0%, respectively. The median survival time were 18.3m (with targeted therapy), 8.8m (without targeted therapy), 23.2m (with primary lesion), 8.4m (without primary lesion), The 1-year, 2-year, 3-year and 5-year OS were 53.3% vs. 26.7%, 40% vs. 0%, 23.3% vs. 0% and 6.7% vs. 0% for patients with targeted therapy vs. without targeted therapy, respectively. The 1-year, 2-year, 3-year and 5-year OS were 85.7% vs. 261%, 42.9% vs. 13%, 28.6% vs. 0% and 14.3% vs. 0% for patients with primary lesion vs. without primary lesion, respectively. 20 patients were interrogated genes using NGS of ctDNA. 80% of patients exhibited ctDNA alterations; TP53-associated genes were most commonly altered (13/20,65%) followed by genes involved in the MAPK pathway (20%), PI3K signaling (10%) and the cell cycle machinery (5%). The genomic profiles help guide treatment in 4 cases. Conclusions: CUPS has a poor prognosis. The pathological type is mostly adenocarcinoma, and lymph node metastasis is the first diagnosis. Chemotherapy is still the main treatment method. Molecular detection is helpful for individualized treatment.