Treatment summary NSCLC and CUP

Treatment of metastatic NSCLC is based on several factors: histology; performance status; presesence or absence or central nervous system involvement; PD-L1 expression (in tumor-, or surrounding-cells, or both); and presence or absence of actionable targets, including recurrent genomic alterations. A detailed description of all potential treatment strategies is beyond the scope of this article. But, it can be said that targeted therapy is the preferred initial option in patients with actionable mutations such as EGFR, ALK, and ROS1. Targeted therapy is also recommended in second-line therapy when appropriate. For patients without actionable mutations, use of immunotherapy has become the standard of care. Single-agent pembrolizumab is approved for NSCLC with high PD-L1 expression (≥50%); platinum-based chemotherapy plus pembrolizumab, regardless of PD-L1 expression, is approved for metastatic NSCLC. For non-squamous metastatic NSCLC, carboplatin plus paclitaxel plus bevacizumab plus atezolizumab is an option as first-line therapy in wild-type EGFR and ALK, and as the treatment of choice in mutated EGFR and ALK when targeted therapy is no longer an option. The combination of immune checkpoint inbitors, nivolumab plus ipilimumab, is also an option with level I evidence in advanced NSCLC. The median survival with these strategies has increased from about 1 year in the chemotherapy era, to about 3 years for EGFR and ALK mutated tumors treated with targeted therapy. Immunotherapy with or without chemotherapy has increased median survival to 17-30 months. It is very significant that about 14% of patients treated in second line with nivolumab, an immune checkpoint inhibitor, are alive after a 4-year follow-up. Cure is a distinct possibility for this subgroup.

Treatment of CUP is based first on recognition of specific good prognosis subgroups using clincal and pathological criteria. Treatment of good prognosis CUP can be homologated to a number of distinct treatment algorithms of corresponding cancers of known primary site. Treatment outcomes of said good prognosis CUP are identical to their known primary site counterpart. Remaining CUP patients belong to the poor prognosis group since median overall survival is only 11 months with combination chemotherapy (with a platinum plus a taxane, in most centers). Attempts to classify cell lineage using immunohistochemistry, or PCR-based gene expression assays, have not become standard of care for a number of reasons. Among these, is lack of robust data supporting cell lineage-directed therapy with well conducted clinical trials.

Abstract sample

V1

Progression-Free Survival (PFS) in a Case-Series of Patients Treated With Palbociclib (Palb) for Metastatatic Breast Cancer (MBC) in Medellín, Colombia.

Authors: Diego Morán, Beatriz Preciado, Camila Lema, Mauricio Luján, Ruben D. Salazar, Alicia Henao, Andrés Yepes, Mauricio Lema
Affiliation: Clínica de Oncología, Astorga, Medellín.

Introduction: In Colombia, 3,702 people each year die of MBC, and it accounts for 8% of cancer related deaths. Endocrine therapy (ET) is the backbone for the initial therapy for most patients with Hormone-Receptor Positive / HER2 negative (HR+/HER2-) MBC. Disease control over several months is the rule, responses are infrequent, and eventual progression is the rule. The advent of aromatase inhibitors (AI) and fulvestrant (Fulv) have improved PFS and overall survival (OS) over older agents. With AI and/or Fulv in first-line (1L) ET the expected PFS and OS are about 14 months and 25 months, respectively. The addition of cdk4/6 inhibitors (iCDK) to ET has improved PFS and OS. These results are consistent accross several trials, with an expected PFS of about 25 months and 10 months when iCDK are added to ET in 1L, and 2L, respectively. It is unknown if disease control can be achieved to the same extent with the use of iCDK in Colombia. This study aims to describe the PFS of patients treated with iCDK + ET in 1L or 2L therapy for MBC in a cancer care facility in Medellín, Colombia.

Methods: This is a case-series of  all consecutive women with HR+/HER2- MBC treated with Palb (an iCDK) plus ET in the Clínica de Oncología Astorga, in Medellín, Colombia. Demographic data, as well as line of therapy in which Palb was used (1L vs 2L, and later), endocrine sensitivity (ES) defined as either one of the following: de-novo MBC or MBC that developed no sooner that 2 years of adjuvant ET was adjudicated. PFS was defined as the time elapsed from iCDK initiation and evidence of disease progression or death. OS was definde as the time elapsed from iCDK initiation and death. Descriptive statistics and Kaplan-Meier survival curves were devised. 

Results: 31 patients were included in the analysis. No patient meeting the inclusion criteria was excluded. Median age was .... (range, ). Median time from breast-cancer diagnosis and MBC was ---- months (range,  ). De novo MBC were --- (%). Palb was used in 1L and 2L in ---(%) and ---(%), respectively.  XX patients (%) were ES. Letrozole (1L) and fulv (2L+) were the ET of ---- (%), ---(%) of patients, respectively. Treatment discontinuation was due to progressive disease in ---(%, 95% CI, --- to ----), and toxicity in --- (%, 95% CI, --- to ----). Median PFS was ---- (95% CI, --- to ----) months , --- (95% CI, --- to ----) months, --- (95% CI, --- to ----) months for the overall, 1L, and 2L, patient population, respectively (p= ..., NS). Median PFS was ---- (95% CI, --- to ----) months , --- (95% CI, --- to ----) months,  for the ES and the non-ES population, respectively (p=..., NS).

Conclusion: In this case-series comprising patients treated in the real-world setting in Colombia we failed to reach the expected PFS with the use of Palb + ET. Small sample size and the retrospective nature of this study are its main limitations, and generalization of its results cannot be supported. 

Number of words: 519

V2

Progression-Free Survival (PFS) in a Case-Series of Patients Treated With Palbociclib (palb) for Metastatatic Breast Cancer (MBC) in Medellín, Colombia.

Authors: Diego Morán, Beatriz Preciado, Camila Lema, Mauricio Luján, Ruben D. Salazar, Alicia Henao, Andrés Yepes, Mauricio Lema
Affiliation: Clínica de Oncología, Astorga, Medellín.

Introduction: Endocrine therapy (ET) is the backbone for the initial therapy in Hormone-Receptor Positive / HER2 negative (HR+/HER2-) MBC. PFS and OS are 14 months and 25 months with fulvestrant (fulv) in first-line (1L), respectively. Aromatase inhibitors (AI) in 1L have slightly inferior results. The addition of palbociclib (palb), a cdk4/6 inhibitor, to ET has improved PFS both in 1L, and in subsequent lines (2L+), in combination with letrozole (an AI) and fulv, respectively. The expected PFS in 1L and 2L+ are 25 months and 10 months, respectively. Disease control is supererior for Endocrine sensitive (ES) disease defined as either de-novo MBC or MBC arising after at least 2 years of adjuvant ET. Low-risk (LR) MBC, defined as metastatic disease confined only to bone/soft-tissue, also exhibit superior PFS to palb + ET. It is unknown if disease control can be achieved to the same extent with the use of palb+ET in Colombia. This study aims to describe the PFS of patients treated with palb+ET in 1L or 2L+  in a cancer center in Medellín, Colombia.

Methods: This is a case-series of palb+ET-treated patients at the Clínica de Oncología Astorga, in Medellín, Colombia. All consecutive patients fulfilling all of the following criteria were included: 1. MBC, 2. HR+, 3. HER2-, and therapy with an palb+ET. Key variables collected included: type of metastatic disease (LR vs non-LR), line in which palb+ET was used (1L vs 2L+), endocrine sensitivity (ES vs non-ES), PFS (time from palb+ET initiation to disease progression or death), and OS (time from palb+ET initiation to death). Kaplan-Meier survival curves were devised. 

Results: All 31 patients fulfilling the inclusion criteria were included. None were excluded. Median age was .... (range, ). Median time from breast-cancer diagnosis and MBC was ---- months (range,  ). De novo MBC were --- (%). --- (%) and ---- (%) patients presented with LR and ES MBC, respectively. Palb was used in 1L and 2L in ---(%) and ---(%), respectively.  Letrozole (1L) and fulv (2L+) were the ET in ---- (%), ---(%), respectively. Treatment discontinuation was due to progressive disease in ---(%, 95% CI, --- to ----), and toxicity in --- (%, 95% CI, --- to ----). Median PFS was ---- (95% CI, --- to ----) months , --- (95% CI, --- to ----) months, --- (95% CI, --- to ----) months for the overall, 1L, and 2L, patient population, respectively (p= ..., NS). Median PFS was ---- (95% CI, --- to ----) months , --- (95% CI, --- to ----) months,  ---- (95% CI, --- to ----) months, ---- (95% CI, --- to ----) months for the LR, non-LR, ES and non-ES population, respectively. OS was ---- (95% CI, --- to ----) months, ---- (95% CI, --- to ----) months in 1L and 2L+, respectively.

Conclusion: In this case-series comprising patients treated in the Real-World setting in Colombia we failed to reach the expected PFS with the use of Palb + ET. The small sample size and the retrospective nature of this study are its main limitations. Generalization of these results cannot be supported.

524 words.

V3.

Progression-Free Survival (PFS) in a Case-Series of Patients Treated With Palbociclib (palb) for Metastatatic Breast Cancer (MBC) in Medellín, Colombia.

Authors: Diego Morán, Beatriz Preciado, Camila Lema, Mauricio Luján, Ruben D. Salazar, Alicia Henao, Andrés Yepes, Mauricio Lema
Affiliation: Clínica de Oncología, Astorga, Medellín.

Introduction: The addition of palbociclib, an oral cdk4/6 inhibitor, to endocrine therapy (palb+ET) has improved PFS in Hormone-Receptor Positive / HER2 negative (HR+/HER2-) MBC in both first- (1L) and subsequent lines (2L+). The expected PFS in 1L (with letrozole, an aromatase inhibitor) and 2L+ (with fulvestrant) are 24.8 months and 9.5 months, respectively. Palb+ET PFS is superior in endocrine sensitive (ES) disease (de novo MBC or MBC with at least 2-year control with ET), and in Low-risk (LR) MBC (bone/soft tissue only metastases). It is unknown whether the same PFS can be achieved with palb+ET in Colombia. This study describe the PFS of palb+ET treated patients at the Clínica de Oncología Astorga (Astorga) in Medellín, Colombia.

Methods: This is a case-series of palb+ET-treated patients at Astorga. All consecutive patients fulfilling all the following criteria were included: 1. MBC, 2. HR+, 3. HER2-, 3. Treatment with palb+ET. Main variables: type of metastatic disease (LR vs non-LR), line in which palb+ET was used (1L vs 2L+), endocrine sensitivity (ES vs non-ES), PFS (time from palb+ET initiation to disease progression or death), and OS (time from palb+ET initiation to death). Kaplan-Meier survival curves were devised. 

Results: All 31 patients fulfilling the inclusion criteria were included. Median age was .... (range, ). Median time from breast-cancer diagnosis and MBC was ---- months (range,  ). De novo MBC were --- (%). --- (%) and ---- (%) patients presented with LR and ES MBC, respectively. Palb was used in 1L and 2L in ---(%) and ---(%), respectively.  Letrozole (1L) and fulv (2L+) were the ET in ---- (%), ---(%), respectively. Treatment discontinuation was due to progressive disease in ---(%, 95% CI, --- to ----), and toxicity in --- (%, 95% CI, --- to ----). Median PFS was ---- (95% CI, --- to ----) months , --- (95% CI, --- to ----) months, --- (95% CI, --- to ----) months for the overall, 1L, and 2L, patient population, respectively (p= ..., NS). Median PFS was ---- (95% CI, --- to ----) months , --- (95% CI, --- to ----) months,  ---- (95% CI, --- to ----) months, ---- (95% CI, --- to ----) months for the LR, non-LR, ES and non-ES population, respectively. OS was ---- (95% CI, --- to ----) months, ---- (95% CI, --- to ----) months in 1L and 2L+, respectively.

Conclusion: In this case-series comprising patients treated in the Real-World setting in Colombia we failed to reach the expected PFS with the use of palb+ET. The small sample size and the retrospective nature of this study are its main limitations. Generalization of these results cannot be supported.

451 words.

V4

Progression-Free Survival (PFS) in a Case-Series of Patients Treated With Palbociclib (palb) for Metastatatic Breast Cancer (MBC) in Medellín, Colombia.

Authors: Diego Morán, Beatriz Preciado, Camila Lema, Mauricio Luján, Ruben D. Salazar, Alicia Henao, Andrés Yepes, Mauricio Lema

Affiliation: Clínica de Oncología, Astorga, Medellín.

Introduction: Addition of palbociclib, an oral cdk4/6 inhibitor, to Endocrine Therapy (palb+ET) has improved PFS in Hormone-Receptor Positive / HER2 negative (HR+/HER2-) MBC in both first- (1L) and subsequent-lines (2L+). Expected PFS in 1L (with letrozole, an aromatase inhibitor) and 2L+ (with fulvestrant) are 25- and 10-months, respectively. Palb+ET PFS is superior in endocrine sensitive (ES) disease (de novo MBC or ≥2-yr control with ET), and in Low-risk (LR) MBC (bone/soft tissue only metastases). It is unknown whether the same PFS can be achieved with palb+ET in Colombia. This study describe the PFS of palb+ET treated patients at the Clínica de Oncología Astorga (Astorga) in Medellín, Colombia.

Methods: This is a case-series of palb+ET-treated patients at Astorga. All consecutive patients fulfilling all the following criteria were included: 1. MBC, 2. HR+/HER2-, 3. Treatment with palb+ET. Main variables: type of metastatic disease (LR vs non-LR), line in which palb+ET was used (1L vs 2L+), endocrine sensitivity (ES vs non-ES), PFS (time from palb+ET initiation to disease progression or death), and OS (time from palb+ET initiation to death). Kaplan-Meier survival curves were devised. 

Results: All 31 patients fulfilling the inclusion criteria were included. Median age was .... (range, ). Median time from breast-cancer diagnosis and MBC was ---- months (range,  ). De novo MBC were --- (%). --- (%) and ---- (%) patients presented with LR and ES MBC, respectively. Palb was used in 1L and 2L in ---(%) and ---(%), respectively.  Letrozole (1L) and fulv (2L+) were the ET in ---- (%), ---(%), respectively. Treatment discontinuation was due to progressive disease in ---(%, 95% CI, --- to ----), and toxicity in --- (%, 95% CI, --- to ----). Median PFS was ---- (95% CI, --- to ----) months , --- (95% CI, --- to ----) months, --- (95% CI, --- to ----) months for the overall, 1L, and 2L, patient population, respectively (p= ..., NS). Median PFS was ---- (95% CI, --- to ----) months , --- (95% CI, --- to ----) months,  ---- (95% CI, --- to ----) months, ---- (95% CI, --- to ----) months for the LR, non-LR, ES and non-ES population, respectively. OS was ---- (95% CI, --- to ----) months, ---- (95% CI, --- to ----) months in 1L and 2L+, respectively.

Conclusion: In this case-series comprising patients treated in a Real-World Setting in Colombia we failed to reach the expected PFS with the use of Palb+ET. Small sample size and the retrospective nature are  the main study limitations. Generalization of these results cannot be supported.

 435 words.

Bladder cancer question

Since I have no internet, I would like to ask you if one approach for 1L metastatic UC with low disease burden can be treated with single-agent IO (we expect ORR: 30%, and DoR of 25 months). Chemo-IO have a higher ORR, but they reflect the relatively meaningless chemo-driven response. On patients with high tumor burden, maybe we should treat with chemo as induction, followed by avelumab (or whatever IO agent available).

Learning English 1 - Welcome to a meeting

 Good morning. It is an honor to host this meeting.  Over the last fifteen years, the treatment landscape of metastatic renal-cell carcinoma has evolved from a highly toxic and largely ineffective cytokine-based therapy, to a staggering number of highly active agents, that include: oral multikinase inhibitors, anti-angiogenic monoclonal antibodies, mTOR inhibitors and, lately, immunotherapy with both anti-PD1 and anti-CTLA4 agents. What to do in first-line therapy has become frightening due to the realization that not all metastatic kidney cancers are created equal, compounded by the sheer number of available options of single-agent and combination therapies. Over the next two hours we will discuss the fist-line options in mRCC with the help of renowned experts in the field. Through research and academia, each one of them has shaped the field. They are: Dr. Enrique Grande, from the MD Anderson, in Madrid - Spain; Dr. Laurence Albiges, from the Institute Gustave-Roussy, in Paris - France; Dr. Ignacio Duran, from the "Hospital de Valdecillas", in Santander - Spain; and Thomas Powles, who works at Barts Hospital, in London - England. We hope to better inform our treatment decisions for the benefit of our patients. This meeting would not be possible without the support of BMS. We will begin with Dr. Grande's presentation: "The changing landscape of 1L mRCC". Welcome, Dr. Grande...

24.10.2020.

Sofía Gómez Uribe y su record en deep diving

Cuento... (Versión preliminar)

Les voy a contar como casi me muero el otro día. Resulta que me compré una de esas cámaras satelitales que ven perfectamente todo lo que ocurre en un área extensa. La prendí, y lo primero que me llamó la atención fue un vagón de tren que casi volaba desde una colina. Había algo, fuera de control, en su apariencia. Lo que me alarmó es que ese vagón se acercaba a un cruce ferroviario, de esos que se bifurcan. En sí mismo, ustedes dirán, no hay razón para preocuparse. Los cruces ferroviarios son muy comunes. Estoy de acuerdo. Es lo que había inmediatamente DESPUÉS de cada cruce lo que me preocupó. Por un lado, sobre la vía ferroviaria estaba la Madre Superiora del convento vecino. A ella le gustaba orar con los ojos cerrados, y oyendo su iPhone, todos los días sobre la vía, justo después del cruce. Al otro lado había una gran convención de gordos no contritos, que se reunían a su ya tradicional festival de la gula. Los obesos pecadores no eran muchos, pero ocupaban literalmente TODOS los espacios, y se apiñaban sobre la vía ferroviaria de la otra vía después de la bifurcación. En un momento dado, siempre había diez gordos sobre la vía ferroviaria. La cosa era trágica, si el vagón se iba por la izquierda... Baaammm, adiós monja. Si se iba por la derecha, bye-bye diez gordos. Esa cámara era la machera porque se podía ver a dónde iba ir el vagón. Vi que la bifurcación iba a la derecha. Los gordos estaban en peligro. Por muchas razones yo hubiera preferido que fuera por el lado de la monja, pero ese es otro tema. A unos pocos metros de la bifurcación, pero demasiado lejos de los que estaban en la vía, estaba una niñita que estudiaba en el colegio de monjas. La niñita era la encargada de mover una palanca que cambiaba el cruce de la bifurcación del tren. La niñita vio con horror como ese vagón desbocado se dirigía a toda velocidad ella. Se fijó, y se tranquilizó al ver que la bifurcación estaba hacia la derecha, así que la madre superiora no corría peligro. Miró a la izquierda, y vio la convención de gordos que invadían incluso la vía ferroviaria. Se dio cuenta que había muchos que iban a ser atropellados por el vagón... Algún tiempo después me contó que en ese momento ella se preguntó: "Qué debo hacer? Puedo mover la palanca para salvar a muchos, pero mataría a la madre superiora. O no hago nada... Alabado sea Dios". No hizo nada y... adió gorditos. Igual, "ellos eran pecadores - glotones - así que el mundo no perdió nada importante, me explicó". Además, si hubiera movido la palanca hubiera sido monjicidio por tren, y de lo poco que le ensañaron las monjas es "no matarás", que era una ley de Dios.

Aterrado por el gordicidio pues me sentía identificado, vi como el vagón sólo perdió un poco de velocidad, y continuó raudo por la vía, la derecha. Alcanzo a ver una segunda bifurcación, esta vez se dividía en dos vías, una arriba y otra abajo. Pero también logré identificar situaciones de peligro en cada una de las bifurcaciones. En la vía de arriba estaba el dueño de la finca, un hombre opulento y egoísta que sólo se preocupaba por su bienestar. En la de abajo estaban cinco jornaleros, empleados de la finca, haciéndole mantenimiento a la vía. La bifurcación estaba dirigida hacia los jornaleros. La palanca de la bifurcación estaba manejada por un sindicalista de la finca. Éste vio como sus compañeros corrían peligro, y se dio cuenta que si movía la palanca, el vagón se iría por la otra vía. Se dio cuenta que el patrón iba a ser atropellado. Para él era fácil, todos somos iguales, y cinco vidas son más importantes que una. Así que movió la palanca. Adiós patrón. Igual, no se perdió mucho, ese señor era muy mal patrón.

El vagón siguió su camino como si nada. Alcancé a observar cómo ya estaba muy cerca de donde yo estaba, y me di cuenta de una tercera bifurcación. Esta vez era atrás y adelante. La vía de atrás impactaría sobre una roca atravesada que si se golpeaba rompía los muros de contención de una represa de agua. El derramamiento de la represa ahogaría a una villa con cien personas en un minuto. Me dio tranquilidad al ver que yo tenía control sobre la palanca de la bifurcación. Rápidamente me di cuenta que la vía de adelante me mataría a mí. Con el vagón casi encima, me fijé en la dirección de la bifurcación, y me di cuenta que me iba a matar...

Los 7 pecados capitales al hablar

Escucharla al hablar era una desgracia. Para ella, todo estaba mal. Era chismosa, envidiosa, quejumbrosa. Culpaba a todo el mundo - menos a ella - de todo lo malo; además, inventaba excusas y exageraciones. Por si fuera poco, confundía sus opiniones con los hechos. No había honestidad, integridad, ni autenticidad. En fin, no había amor. Su lengua viperina sólo destruía y quien la escuchaba quedaba disminuido...

(Idea tomada de Julian Treasure).