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Papers by Francisco Pietro Oliveira Orlandi

International Journal of Cancer

KEYNOTE‐033 (NCT02864394) was a multicountry, open‐label, phase 3 study that compared pembrolizum... more KEYNOTE‐033 (NCT02864394) was a multicountry, open‐label, phase 3 study that compared pembrolizumab vs docetaxel in previously treated, programmed death‐ligand 1 (PD‐L1)‐positive, advanced non‐small cell lung cancer (NSCLC), with most patients enrolled in mainland China. Eligible patients were randomized (1:1) to pembrolizumab 2 mg/kg or docetaxel 75 mg/m2 every 3 weeks. Primary endpoints were overall survival (OS) and progression‐free survival and were evaluated sequentially using stratified log‐rank tests, first in patients with PD‐L1 tumor proportion score (TPS) ≥50% and then in patients with PD‐L1 TPS ≥1% (significance threshold: P < .025, one‐sided). A total of 425 patients were randomized to pembrolizumab (N = 213) or docetaxel (N = 212) between 8 September 2016 and 17 October 2018. In patients with a PD‐L1 TPS ≥50% (n = 227), median OS was 12.3 months with pembrolizumab and 10.9 months with docetaxel; the hazard ratio (HR) was 0.83 (95% confidence interval [CI]: 0.61‐1.14;...

Journal of Clinical Oncology, 2021

e20535 Background: Lung cancer is the leading cause of cancer related death worldwide and so is e... more e20535 Background: Lung cancer is the leading cause of cancer related death worldwide and so is expected in Chile in 2021 accoding to Globocan, with a 12.4% mortality rate last year. Among NSCLC, 35 to 40% present as locally advanced disease, most of them non surgical candidates. Current standard of treatment is platinum-based doublet with concurrent Radiotherapy plus adyuvant durvalumab since 2018. Still many controversies related to different approaches are not settled. Few literature is available concerning a less aggressive approach in order to achieve a more tolerable treatment for the patient preserving effectiveness. Many patients compromise the treatment compliance due to early toxicities. We present our preliminary results of local data consisting in weekly cisplatin plus concurrent standard dose of radiotherapy. Methods: We performed a retrospective review of local database for stage III unresectable NSCLC between 2013 to 2019. Baseline clinical data , treatment modality, ...

Journal of Clinical Oncology, 2021

9038 Background: In the phase 3 KEYNOTE-598 study (NCT03302234), OS (HR, 1.08; 95% CI, 0.85–1.37;... more 9038 Background: In the phase 3 KEYNOTE-598 study (NCT03302234), OS (HR, 1.08; 95% CI, 0.85–1.37; P = 0.74) and PFS (1.06; 95% CI, 0.86–1.30; P = 0.72) were not improved for pembro + ipi vs pembro + placebo in patients (pts) with previously untreated metastatic NSCLC with PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK genomic alterations. Incidence of treatment-related grade 3–5 AEs, fatal AEs, and AEs leading to discontinuation was higher with pembro + ipi vs pembro + placebo. We present prespecified patient-reported outcome (PRO) analyses from KEYNOTE-598. Methods: Pts (n = 568) with previously untreated stage IV NSCLC with PD-L1 TPS ≥50% were randomized 1:1 to pembro 200 mg Q3W for up to 35 cycles + ipi 1 mg/kg or placebo Q6W for up to 18 cycles. The EORTC QLQ-C30, QLQ-LC13, EQ-5D-5L, and NSCLC-SAQ were administered at cycles 1‒7, then every 3 cycles through cycle 19, and every 4 cycles until PD or a maximum of 35 cycles. Change from baseline in global health status...

JCO Global Oncology, 2021

PURPOSE To present a summary of the treatment and follow-up recommendations for the biochemical r... more PURPOSE To present a summary of the treatment and follow-up recommendations for the biochemical recurrence in castration-sensitive prostate cancer (PCa) acquired through a questionnaire administered to 99 PCa experts from developing countries during the Prostate Cancer Consensus Conference for Developing Countries. METHODS A total of 27 questions were identified as related to this topic from more than 300 questions. The clinician's responses were tallied and presented in a percentage format. Topics included the use of imaging for staging biochemical recurrence, treatment recommendations for three different clinical scenarios, the field of radiation recommended, and follow-up. Each question had 5-7 relevant response options, including “abstain” and/or “unqualified to answer,” and investigated not only recommendations but also if a limitation in resources would change the recommendation. RESULTS For most questions, a clear majority (> 50%) of clinicians agreed on a recommended ...

JCO Global Oncology, 2021

PURPOSE International guideline recommendations may not always be extrapolated to developing coun... more PURPOSE International guideline recommendations may not always be extrapolated to developing countries where access to resources is limited. In metastatic castration-sensitive prostate cancer (mCSPC), there have been successful drug and imaging advancements that were addressed in the Prostate Cancer Consensus Conference for Developing Countries for best-practice and limited-resource scenarios. METHODS A total of 24 out of 300 questions addressed staging, treatment, and follow-up for patients with mCSPC both in best-practice settings and resource-limited settings. Responses were compiled and presented in percentage of clinicians supporting each response. Questions had 4-8 options for response. RESULTS Recommendations for staging in mCSPC were split but there was consensus that chest x-ray, abdominal and pelvic computed tomography, and bone scan should be used where resources are limited. In both de novo and relapsed low-volume mCSPC, orchiectomy alone in limited resources was favored...

Molecular and Clinical Oncology, 2021

Lung cancer is a leading cause of cancer-related deaths in Latin America, with non-small cell lun... more Lung cancer is a leading cause of cancer-related deaths in Latin America, with non-small cell lung cancer (NSCLC) being the most prevalent. The current study aimed to report real-world data on epidermal growth factor receptor (EGFR) mutational testing and treatment regimens at diagnosis and progression in patients with metastatic NSCLC across four Latin American countries (Argentina, Chile, Colombia and Uruguay). A retrospective, multicenter, observational study was conducted in patients with NSCLC using medical records from participating countries. The study population was categorized into two cohorts: Cohort 1 comprised of newly diagnosed, treatment-naïve patients with stage IV NSCLC; and cohort 2 comprised of stage IV NSCLC EGFR mutation (EGFRm)-positive patients who had progressed after first-or second-generation EGFR-tyrosine kinase inhibitor (TKI) treatment. Measures included demographic variables, health characteristics, treatment regimen, molecular testing rate and turnaround time at diagnosis and at progression for cohorts 1 and 2, respectively. Descriptive statistics were used to summarize all study measures. Of the 462 patients enrolled, 431 were newly diagnosed or treatment naïve with metastatic NSCLC. In cohort 1, the majority of patients with private health insurance (57.31%) underwent molecular diagnosis while only 41.3% of patients within the public sector had access to testing. The average molecular testing rate in cohort 1 varied across countries, with Argentina having the highest testing rate (79%) and Uruguay the lowest (27.63%). EGFRm was observed in 22% of patients. Cohort 2 comprised 31 patients who had progressed after first-or second-generation EGFR-TKI treatment and of these, only 22 (70.97%) underwent testing after progression. Access to molecular testing is still a challenge impacting the choice of first-line treatment in Latin American patients with NSCLC.

Journal of Thoracic Oncology, 2021

INTRODUCTION Final overall survival (OS) analyses are presented for EGFR mutations and liver or b... more INTRODUCTION Final overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase III IMpower150 study (NCT02366143) evaluating atezolizumab+bevacizumab+carboplatin/paclitaxel (ABCP) or atezolizumab+carboplatin/paclitaxel (ACP) vs bevacizumab+carboplatin/paclitaxel (BCP). METHODS Overall, 1202 patients (intention-to-treat [ITT] population) with chemotherapy-naive, metastatic, nonsquamous non-small cell lung cancer were randomized to ABCP, ACP or BCP. Patients with treated, stable brain metastases were permitted. OS was assessed in EGFR mutations and baseline liver metastases subgroups; rate and time to development (TTD) of new brain metastases was assessed in ITT patients. RESULTS At data cutoff (September 13, 2019; median follow-up, 39.3 months), OS improvements were sustained with ABCP versus BCP in sensitizing EGFR mutations (all: hazard ratio [HR] 0.60; 95% CI: 0.31-1.14; prior tyrosine kinase inhibitor [TKI]: HR 0.74; 95% CI: 0.38-1.46) and baseline liver metastases (HR 0.68; 95% CI: 0.45-1.02) subgroups. ACP did not show survival benefit versus BCP in sensitizing EGFR mutations (all: HR 1.0; 95% CI: 0.57-1.74; prior TKI: HR 1.22; 95% CI: 0.68-2.22) or liver metastases (HR 1.01; 95% CI: 0.68-1.51) subgroups. Overall, 100 patients (8.3%) developed new brain metastases. While not formally evaluated, an improvement toward delayed TTD was seen with ABCP vs BCP (HR, 0.68; 95% CI: 0.39-1.19). CONCLUSIONS This final exploratory analysis showed OS benefits for ABCP versus BCP in patients with sensitizing EGFR mutations, including those with prior TKI failures, and with liver metastases, although these results should be interpreted with caution. The impact of ABCP on delaying the development of new brain lesions requires further investigation.

Journal of Thoracic Oncology, 2021

INTRODUCTION We report final overall survival (OS) analyses of atezolizumab-carboplatin-paclitaxe... more INTRODUCTION We report final overall survival (OS) analyses of atezolizumab-carboplatin-paclitaxel (ACP [experimental arm]) and OS data with ≈ 39.8 months of median follow-up with atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP) versus bevacizumab-carboplatin-paclitaxel (BCP) in chemotherapy-naive patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) in the Phase III IMpower150 study (NCT02366143). METHODS In this randomized, open-label study (N = 1202), coprimary endpoints included investigator-assessed progression-free survival and OS in intention-to-treat (ITT) wild-type (WT; no EGFR or ALK alterations) patients. Secondary and exploratory endpoints included OS in ITT and PD-L1 subgroups defined by the VENTANA SP142 and SP263 immunohistochemistry assays. RESULTS At the final analysis with ACP vs BCP (data cutoff: September 13, 2019; minimum follow-up: 32.4 months), ACP showed numerical, but not statistically significant, improvements in OS (ITT-WT: median OS [mOS] 19.0 vs 14.7 months; hazard ratio [HR] 0.84; 95% CI, 0.71-1.00). OS benefit was sustained with ABCP vs BCP (ITT-WT: 19.5 vs 14.7 months; HR 0.80; 95% CI, 0.67-0.95). Exploratory analyses in the SP142-defined PD-L1 subgroups showed longer median OS with ABCP and ACP vs BCP in PD-L1-high and PD-L1-positive subgroups; in the PD-L1-negative subgroups, median OS was similar with ACP and ABCP vs BCP. Safety was consistent with that in earlier analyses (data cutoff: Jan 22, 2018). CONCLUSIONS At the final IMpower150 OS analysis, ACP showed numerically, but not statistically significant, OS improvement vs BCP. Updated data with an additional 20 months of follow-up showed continued OS improvement with ABCP vs BCP in all patients.

Journal of Clinical Oncology, 2021

PURPOSE: IMpower133 (ClinicalTrials.gov identifier: NCT02763579 ), a randomized, double-blind, ph... more PURPOSE: IMpower133 (ClinicalTrials.gov identifier: NCT02763579 ), a randomized, double-blind, phase I/III study, demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to carboplatin plus etoposide (CP/ET) for first-line (1L) treatment of extensive-stage small-cell lung cancer (ES-SCLC) resulted in significant improvement in overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET. Updated OS, disease progression patterns, safety, and exploratory biomarkers (PD-L1, blood-based tumor mutational burden [bTMB]) are reported. PATIENTS AND METHODS: Patients with untreated ES-SCLC were randomly assigned 1:1 to receive four 21-day cycles of CP (area under the curve 5 mg per mL/min intravenously [IV], day 1) plus ET (100 mg/m2 IV, days 1-3) with atezolizumab (1,200 mg IV, day 1) or placebo, and then maintenance atezolizumab or placebo until unacceptable toxicity, disease progression, or loss of clinical benefit. Tumor specimens were collec...

Journal of Thoracic Oncology, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Journal of Clinical Oncology, 2021

PURPOSE Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lu... more PURPOSE Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. METHODS In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234 ), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. RESULTS Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 mon...

Journal of Clinical Oncology, 2021

LBA5 Background: Relapse after surgery for high-risk clear cell RCC (ccRCC) is associated with sh... more LBA5 Background: Relapse after surgery for high-risk clear cell RCC (ccRCC) is associated with shortened life expectancy. Effective perioperative therapy to reduce this risk remains an unmet need. Adjuvant immune therapy is an attractive potential strategy for these pts. We conducted the KEYNOTE-564 trial to evaluate pembro vs placebo as adjuvant therapy for pts with RCC. Methods: KEYNOTE-564 is a phase III multicenter trial of pembro vs placebo in pts with histologically confirmed ccRCC, with intermediate-high risk (pT2, Gr 4 or sarcomatoid, N0 M0; or pT3, any Gr, N0 M0), high risk (pT4, any Gr, N0 M0; or pT any stage, any Gr, N+ M0), or M1 NED (no evidence of disease after primary tumor + soft tissue metastases completely resected ≤1 year from nephrectomy) (Leibovich et al, 2003; Fuhrman et al, 1982). Pts had undergone surgery ≤12 wks prior to randomization; had no prior systemic therapy; had ECOG PS 0 or 1. Study treatment was given for up to 17 cycles (≈1 yr). The primary endpoi...

Journal of Thoracic Oncology, 2021

Annals of Oncology, 2020

Conclusions: In IMpower133, more pts in the atezo + CE arm than in the PBO + CE arm were LTS. Whi... more Conclusions: In IMpower133, more pts in the atezo + CE arm than in the PBO + CE arm were LTS. While sample size was small, exploratory analyses suggest that pts with ES-SCLC can derive benefit from the addition of atezo to chemotherapy regardless of the pt and disease characteristics evaluated, confirming atezo + CE as standard of care for pts with untreated ES-SCLC. Clinical trial identification: NCT02763579.

Annals of Oncology, 2020

Background: CS1001, a full-length, fully human PD-L1 targeted IgG4 (s228p) mAb, was well tolerate... more Background: CS1001, a full-length, fully human PD-L1 targeted IgG4 (s228p) mAb, was well tolerated and had demonstrated promising anti-tumor activities across a range of cancers including NSCLC in phase Ia/Ib study. GEMSTONE-302 is a randomized, double-blind, phase III study to compare the efficacy and safety of chemo with or without CS1001 as 1L treatment for advanced NSCLC. Methods: Eligible pts with untreated advanced NSCLC were stratified by histology (sq vs nsq), PD-L1 expression (1% vs <1%), and ECOG PS (0 vs 1) and randomized 2:1 to receive CS1001 (1200 mg, Q3W, IV)/placebo + chemo up to 4 cycles, followed by CS1001 or placebo maintenance up to 2 yrs. In nsq pts, pemetrexed was also given as maintenance therapy. The primary endpoint is investigator-assessed PFS (RECISIT v1.1). Results: A total of 479 pts (320 in CS1001+chemo, 159 in placebo+chemo) were enrolled in the study. Baseline characteristics were balanced between 2 arms. As of 8 Jun 2020, at the pre-planned PFS interim analysis (median follow-up 8.67 vs 8.34 mo), the mPFS was significantly prolonged in the CS1001+chemo arm (stratified HR 0.50 [0.39-0.64], p<.0001; mPFS 7.8 vs 4.9 mo). ORR was 61.4% and 39.2% in CS1001+chemo and placebo+chemo arms, respectively. OS data was immature, but a clinical benefit trend was observed, (stratified HR 0.66 [0.44-0.97]; mOS NR vs 14.75 mo). Subgroup analyses demonstrated clinical benefits across histology and PD-L1 expression levels. Grade 3 TEAEs were reported in 61.9% and 61.6% of pts in CS1001+chemo and placebo+chemo arms, respectively. The 2 arms had similar safety profile, with the exception of mostly Grade 1 and 2 immune-related AEs in CS1001+chemo arm. No new unexpected safety signals were found. Conclusions: This is the first phase III trial conducted in China on an anti-PD-L1 mAb plus chemo that enrolls advanced, treatment-naive sq and nsq NSCLC pts. CS1001 combined with chemo shows statistically significant and clinically meaningful benefit in PFS with a well-tolerated safety profile against chemo across histology and PD-L1 expression levels. It will potentially become a new SOC for 1L treatment of advanced NSCLC once receiving regulatory approval. Clinical trial identification: NCT03789604.

Cancer Research, 2020

Background: IMpower133 (NCT02763579), a global Phase I/III, randomized, double-blind, placebo (PB... more Background: IMpower133 (NCT02763579), a global Phase I/III, randomized, double-blind, placebo (PBO)-controlled trial, showed that the addition of atezo (anti-PD-L1) to CE for 1L ES-SCLC led to statistically and clinically significant OS and PFS improvement vs CE alone. Here we report updated OS and exploratory analyses. Methods: Pts with untreated ES-SCLC were randomized 1:1 to receive four 21-day cycles of E (100 mg/m2 IV, days 1-3) + C (AUC 5 mg/mL/min IV, day 1) with atezo (1200 mg IV, day 1) or PBO, followed by maintenance therapy with atezo or PBO until intolerable toxicity, progression or loss of clinical benefit. PD-L1 testing was not required for enrollment. Coprimary endpoints were investigator-assessed PFS (RECIST 1.1) and OS. Interim and final OS analyses were planned for ≈240 and ≈306 events, respectively. OS was significant at the interim analysis. Updated OS, exploratory biomarkers and patterns of disease progression were analyzed. Results: 201 and 202 pts were randomi...

Cancer Research, 2020

Background: The Ph III IMpower150 study (NCT02366143) showed PFS and OS benefit with atezo + bev ... more Background: The Ph III IMpower150 study (NCT02366143) showed PFS and OS benefit with atezo + bev + carboplatin (carbo) + paclitaxel (pac; ABCP; Arm B) vs bev + carbo + pac (BCP; Arm C) as 1L treatment (tx) for patients (pts) with metastatic nsq NSCLC. Clinical benefit was also seen in pts with EGFR-mutant or ALK-positive (EGFR/ALK+) tumors. We report the final efficacy analyses from IMpower150, including those of the experimental tx arm evaluating atezo + carbo + pac (ACP; Arm A) vs Arm C. Methods: The randomized, open-label, Ph III IMpower150 study evaluated ACP (Arm A) or ABCP (Arm B) vs BCP (Arm C) in pts with metastatic nsq NSCLC (N = 1202). Key eligibility criteria included no prior chemotherapy, measurable disease per RECIST 1.1 and ECOG PS 0-1. Pts were stratified by sex, baseline liver metastases (mets) and PD-L1 expression. Coprimary endpoints were investigator-assessed PFS and OS in ITT wild-type (WT; no EGFR or ALK genetic alterations) pts. Secondary endpoints included PF...

Journal of Clinical Oncology, 2020

9001 Background: Pembro monotherapy showed durable antitumor activity as third-line or later ther... more 9001 Background: Pembro monotherapy showed durable antitumor activity as third-line or later therapy for metastatic SCLC, leading to FDA approval in that setting. KEYNOTE-604 was a double-blind, phase 3 study of pembro + EP vs placebo + EP as first-line therapy for ES-SCLC (NCT03066778). Methods: Eligible patients (pts) with previously untreated ES-SCLC and no untreated CNS metastases were randomized 1:1 to pembro 200 mg Q3W or saline placebo for up to 35 cycles plus 4 cycles of standard-dose EP. Pts with CR or PR after cycle 4 could receive PCI at investigator discretion. Randomization was stratified by platinum choice (carboplatin vs cisplatin), ECOG PS (0 vs 1), and LDH (≤ULN vs > ULN). Primary endpoints were OS and PFS (RECIST v1.1, blinded central review) in the ITT population. ORR, DOR, and safety were secondary endpoints. OS and PFS treatment differences were assessed by the stratified log-rank test. The protocol specified 2 interim analyses (IAs) and a final analysis (FA)...

Journal of Clinical Oncology, 2020

PURPOSE Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung c... more PURPOSE Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung cancer (SCLC). The randomized, double-blind, phase III KEYNOTE-604 study compared pembrolizumab plus etoposide and platinum (EP) with placebo plus EP for patients with previously untreated extensive-stage (ES) SCLC. METHODS Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks or saline placebo for up to 35 cycles plus 4 cycles of EP. Primary end points were progression-free survival (PFS; RECIST version 1.1, blinded central review) and overall survival (OS) in the intention-to-treat population. Objective response rate (ORR) and duration of response were secondary end points. Prespecified efficacy boundaries were one-sided P = .0048 for PFS and .0128 for OS. RESULTS Of the 453 participants, 228 were randomly assigned to pembrolizumab plus EP and 225 to placebo plus EP. Pembrolizumab plus EP significantly improved PFS (hazard ratio [HR], 0.75; 95% CI, 0.61...

International Journal of Cancer

KEYNOTE‐033 (NCT02864394) was a multicountry, open‐label, phase 3 study that compared pembrolizum... more KEYNOTE‐033 (NCT02864394) was a multicountry, open‐label, phase 3 study that compared pembrolizumab vs docetaxel in previously treated, programmed death‐ligand 1 (PD‐L1)‐positive, advanced non‐small cell lung cancer (NSCLC), with most patients enrolled in mainland China. Eligible patients were randomized (1:1) to pembrolizumab 2 mg/kg or docetaxel 75 mg/m2 every 3 weeks. Primary endpoints were overall survival (OS) and progression‐free survival and were evaluated sequentially using stratified log‐rank tests, first in patients with PD‐L1 tumor proportion score (TPS) ≥50% and then in patients with PD‐L1 TPS ≥1% (significance threshold: P < .025, one‐sided). A total of 425 patients were randomized to pembrolizumab (N = 213) or docetaxel (N = 212) between 8 September 2016 and 17 October 2018. In patients with a PD‐L1 TPS ≥50% (n = 227), median OS was 12.3 months with pembrolizumab and 10.9 months with docetaxel; the hazard ratio (HR) was 0.83 (95% confidence interval [CI]: 0.61‐1.14;...

Journal of Clinical Oncology, 2021

e20535 Background: Lung cancer is the leading cause of cancer related death worldwide and so is e... more e20535 Background: Lung cancer is the leading cause of cancer related death worldwide and so is expected in Chile in 2021 accoding to Globocan, with a 12.4% mortality rate last year. Among NSCLC, 35 to 40% present as locally advanced disease, most of them non surgical candidates. Current standard of treatment is platinum-based doublet with concurrent Radiotherapy plus adyuvant durvalumab since 2018. Still many controversies related to different approaches are not settled. Few literature is available concerning a less aggressive approach in order to achieve a more tolerable treatment for the patient preserving effectiveness. Many patients compromise the treatment compliance due to early toxicities. We present our preliminary results of local data consisting in weekly cisplatin plus concurrent standard dose of radiotherapy. Methods: We performed a retrospective review of local database for stage III unresectable NSCLC between 2013 to 2019. Baseline clinical data , treatment modality, ...

Journal of Clinical Oncology, 2021

9038 Background: In the phase 3 KEYNOTE-598 study (NCT03302234), OS (HR, 1.08; 95% CI, 0.85–1.37;... more 9038 Background: In the phase 3 KEYNOTE-598 study (NCT03302234), OS (HR, 1.08; 95% CI, 0.85–1.37; P = 0.74) and PFS (1.06; 95% CI, 0.86–1.30; P = 0.72) were not improved for pembro + ipi vs pembro + placebo in patients (pts) with previously untreated metastatic NSCLC with PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK genomic alterations. Incidence of treatment-related grade 3–5 AEs, fatal AEs, and AEs leading to discontinuation was higher with pembro + ipi vs pembro + placebo. We present prespecified patient-reported outcome (PRO) analyses from KEYNOTE-598. Methods: Pts (n = 568) with previously untreated stage IV NSCLC with PD-L1 TPS ≥50% were randomized 1:1 to pembro 200 mg Q3W for up to 35 cycles + ipi 1 mg/kg or placebo Q6W for up to 18 cycles. The EORTC QLQ-C30, QLQ-LC13, EQ-5D-5L, and NSCLC-SAQ were administered at cycles 1‒7, then every 3 cycles through cycle 19, and every 4 cycles until PD or a maximum of 35 cycles. Change from baseline in global health status...

JCO Global Oncology, 2021

PURPOSE To present a summary of the treatment and follow-up recommendations for the biochemical r... more PURPOSE To present a summary of the treatment and follow-up recommendations for the biochemical recurrence in castration-sensitive prostate cancer (PCa) acquired through a questionnaire administered to 99 PCa experts from developing countries during the Prostate Cancer Consensus Conference for Developing Countries. METHODS A total of 27 questions were identified as related to this topic from more than 300 questions. The clinician's responses were tallied and presented in a percentage format. Topics included the use of imaging for staging biochemical recurrence, treatment recommendations for three different clinical scenarios, the field of radiation recommended, and follow-up. Each question had 5-7 relevant response options, including “abstain” and/or “unqualified to answer,” and investigated not only recommendations but also if a limitation in resources would change the recommendation. RESULTS For most questions, a clear majority (> 50%) of clinicians agreed on a recommended ...

JCO Global Oncology, 2021

PURPOSE International guideline recommendations may not always be extrapolated to developing coun... more PURPOSE International guideline recommendations may not always be extrapolated to developing countries where access to resources is limited. In metastatic castration-sensitive prostate cancer (mCSPC), there have been successful drug and imaging advancements that were addressed in the Prostate Cancer Consensus Conference for Developing Countries for best-practice and limited-resource scenarios. METHODS A total of 24 out of 300 questions addressed staging, treatment, and follow-up for patients with mCSPC both in best-practice settings and resource-limited settings. Responses were compiled and presented in percentage of clinicians supporting each response. Questions had 4-8 options for response. RESULTS Recommendations for staging in mCSPC were split but there was consensus that chest x-ray, abdominal and pelvic computed tomography, and bone scan should be used where resources are limited. In both de novo and relapsed low-volume mCSPC, orchiectomy alone in limited resources was favored...

Molecular and Clinical Oncology, 2021

Lung cancer is a leading cause of cancer-related deaths in Latin America, with non-small cell lun... more Lung cancer is a leading cause of cancer-related deaths in Latin America, with non-small cell lung cancer (NSCLC) being the most prevalent. The current study aimed to report real-world data on epidermal growth factor receptor (EGFR) mutational testing and treatment regimens at diagnosis and progression in patients with metastatic NSCLC across four Latin American countries (Argentina, Chile, Colombia and Uruguay). A retrospective, multicenter, observational study was conducted in patients with NSCLC using medical records from participating countries. The study population was categorized into two cohorts: Cohort 1 comprised of newly diagnosed, treatment-naïve patients with stage IV NSCLC; and cohort 2 comprised of stage IV NSCLC EGFR mutation (EGFRm)-positive patients who had progressed after first-or second-generation EGFR-tyrosine kinase inhibitor (TKI) treatment. Measures included demographic variables, health characteristics, treatment regimen, molecular testing rate and turnaround time at diagnosis and at progression for cohorts 1 and 2, respectively. Descriptive statistics were used to summarize all study measures. Of the 462 patients enrolled, 431 were newly diagnosed or treatment naïve with metastatic NSCLC. In cohort 1, the majority of patients with private health insurance (57.31%) underwent molecular diagnosis while only 41.3% of patients within the public sector had access to testing. The average molecular testing rate in cohort 1 varied across countries, with Argentina having the highest testing rate (79%) and Uruguay the lowest (27.63%). EGFRm was observed in 22% of patients. Cohort 2 comprised 31 patients who had progressed after first-or second-generation EGFR-TKI treatment and of these, only 22 (70.97%) underwent testing after progression. Access to molecular testing is still a challenge impacting the choice of first-line treatment in Latin American patients with NSCLC.

Journal of Thoracic Oncology, 2021

INTRODUCTION Final overall survival (OS) analyses are presented for EGFR mutations and liver or b... more INTRODUCTION Final overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase III IMpower150 study (NCT02366143) evaluating atezolizumab+bevacizumab+carboplatin/paclitaxel (ABCP) or atezolizumab+carboplatin/paclitaxel (ACP) vs bevacizumab+carboplatin/paclitaxel (BCP). METHODS Overall, 1202 patients (intention-to-treat [ITT] population) with chemotherapy-naive, metastatic, nonsquamous non-small cell lung cancer were randomized to ABCP, ACP or BCP. Patients with treated, stable brain metastases were permitted. OS was assessed in EGFR mutations and baseline liver metastases subgroups; rate and time to development (TTD) of new brain metastases was assessed in ITT patients. RESULTS At data cutoff (September 13, 2019; median follow-up, 39.3 months), OS improvements were sustained with ABCP versus BCP in sensitizing EGFR mutations (all: hazard ratio [HR] 0.60; 95% CI: 0.31-1.14; prior tyrosine kinase inhibitor [TKI]: HR 0.74; 95% CI: 0.38-1.46) and baseline liver metastases (HR 0.68; 95% CI: 0.45-1.02) subgroups. ACP did not show survival benefit versus BCP in sensitizing EGFR mutations (all: HR 1.0; 95% CI: 0.57-1.74; prior TKI: HR 1.22; 95% CI: 0.68-2.22) or liver metastases (HR 1.01; 95% CI: 0.68-1.51) subgroups. Overall, 100 patients (8.3%) developed new brain metastases. While not formally evaluated, an improvement toward delayed TTD was seen with ABCP vs BCP (HR, 0.68; 95% CI: 0.39-1.19). CONCLUSIONS This final exploratory analysis showed OS benefits for ABCP versus BCP in patients with sensitizing EGFR mutations, including those with prior TKI failures, and with liver metastases, although these results should be interpreted with caution. The impact of ABCP on delaying the development of new brain lesions requires further investigation.

Journal of Thoracic Oncology, 2021

INTRODUCTION We report final overall survival (OS) analyses of atezolizumab-carboplatin-paclitaxe... more INTRODUCTION We report final overall survival (OS) analyses of atezolizumab-carboplatin-paclitaxel (ACP [experimental arm]) and OS data with ≈ 39.8 months of median follow-up with atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP) versus bevacizumab-carboplatin-paclitaxel (BCP) in chemotherapy-naive patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) in the Phase III IMpower150 study (NCT02366143). METHODS In this randomized, open-label study (N = 1202), coprimary endpoints included investigator-assessed progression-free survival and OS in intention-to-treat (ITT) wild-type (WT; no EGFR or ALK alterations) patients. Secondary and exploratory endpoints included OS in ITT and PD-L1 subgroups defined by the VENTANA SP142 and SP263 immunohistochemistry assays. RESULTS At the final analysis with ACP vs BCP (data cutoff: September 13, 2019; minimum follow-up: 32.4 months), ACP showed numerical, but not statistically significant, improvements in OS (ITT-WT: median OS [mOS] 19.0 vs 14.7 months; hazard ratio [HR] 0.84; 95% CI, 0.71-1.00). OS benefit was sustained with ABCP vs BCP (ITT-WT: 19.5 vs 14.7 months; HR 0.80; 95% CI, 0.67-0.95). Exploratory analyses in the SP142-defined PD-L1 subgroups showed longer median OS with ABCP and ACP vs BCP in PD-L1-high and PD-L1-positive subgroups; in the PD-L1-negative subgroups, median OS was similar with ACP and ABCP vs BCP. Safety was consistent with that in earlier analyses (data cutoff: Jan 22, 2018). CONCLUSIONS At the final IMpower150 OS analysis, ACP showed numerically, but not statistically significant, OS improvement vs BCP. Updated data with an additional 20 months of follow-up showed continued OS improvement with ABCP vs BCP in all patients.

Journal of Clinical Oncology, 2021

PURPOSE: IMpower133 (ClinicalTrials.gov identifier: NCT02763579 ), a randomized, double-blind, ph... more PURPOSE: IMpower133 (ClinicalTrials.gov identifier: NCT02763579 ), a randomized, double-blind, phase I/III study, demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to carboplatin plus etoposide (CP/ET) for first-line (1L) treatment of extensive-stage small-cell lung cancer (ES-SCLC) resulted in significant improvement in overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET. Updated OS, disease progression patterns, safety, and exploratory biomarkers (PD-L1, blood-based tumor mutational burden [bTMB]) are reported. PATIENTS AND METHODS: Patients with untreated ES-SCLC were randomly assigned 1:1 to receive four 21-day cycles of CP (area under the curve 5 mg per mL/min intravenously [IV], day 1) plus ET (100 mg/m2 IV, days 1-3) with atezolizumab (1,200 mg IV, day 1) or placebo, and then maintenance atezolizumab or placebo until unacceptable toxicity, disease progression, or loss of clinical benefit. Tumor specimens were collec...

Journal of Thoracic Oncology, 2021

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Journal of Clinical Oncology, 2021

PURPOSE Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lu... more PURPOSE Pembrolizumab monotherapy is standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population. METHODS In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234 ), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival. RESULTS Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 mon...

Journal of Clinical Oncology, 2021

LBA5 Background: Relapse after surgery for high-risk clear cell RCC (ccRCC) is associated with sh... more LBA5 Background: Relapse after surgery for high-risk clear cell RCC (ccRCC) is associated with shortened life expectancy. Effective perioperative therapy to reduce this risk remains an unmet need. Adjuvant immune therapy is an attractive potential strategy for these pts. We conducted the KEYNOTE-564 trial to evaluate pembro vs placebo as adjuvant therapy for pts with RCC. Methods: KEYNOTE-564 is a phase III multicenter trial of pembro vs placebo in pts with histologically confirmed ccRCC, with intermediate-high risk (pT2, Gr 4 or sarcomatoid, N0 M0; or pT3, any Gr, N0 M0), high risk (pT4, any Gr, N0 M0; or pT any stage, any Gr, N+ M0), or M1 NED (no evidence of disease after primary tumor + soft tissue metastases completely resected ≤1 year from nephrectomy) (Leibovich et al, 2003; Fuhrman et al, 1982). Pts had undergone surgery ≤12 wks prior to randomization; had no prior systemic therapy; had ECOG PS 0 or 1. Study treatment was given for up to 17 cycles (≈1 yr). The primary endpoi...

Journal of Thoracic Oncology, 2021

Annals of Oncology, 2020

Conclusions: In IMpower133, more pts in the atezo + CE arm than in the PBO + CE arm were LTS. Whi... more Conclusions: In IMpower133, more pts in the atezo + CE arm than in the PBO + CE arm were LTS. While sample size was small, exploratory analyses suggest that pts with ES-SCLC can derive benefit from the addition of atezo to chemotherapy regardless of the pt and disease characteristics evaluated, confirming atezo + CE as standard of care for pts with untreated ES-SCLC. Clinical trial identification: NCT02763579.

Annals of Oncology, 2020

Background: CS1001, a full-length, fully human PD-L1 targeted IgG4 (s228p) mAb, was well tolerate... more Background: CS1001, a full-length, fully human PD-L1 targeted IgG4 (s228p) mAb, was well tolerated and had demonstrated promising anti-tumor activities across a range of cancers including NSCLC in phase Ia/Ib study. GEMSTONE-302 is a randomized, double-blind, phase III study to compare the efficacy and safety of chemo with or without CS1001 as 1L treatment for advanced NSCLC. Methods: Eligible pts with untreated advanced NSCLC were stratified by histology (sq vs nsq), PD-L1 expression (1% vs <1%), and ECOG PS (0 vs 1) and randomized 2:1 to receive CS1001 (1200 mg, Q3W, IV)/placebo + chemo up to 4 cycles, followed by CS1001 or placebo maintenance up to 2 yrs. In nsq pts, pemetrexed was also given as maintenance therapy. The primary endpoint is investigator-assessed PFS (RECISIT v1.1). Results: A total of 479 pts (320 in CS1001+chemo, 159 in placebo+chemo) were enrolled in the study. Baseline characteristics were balanced between 2 arms. As of 8 Jun 2020, at the pre-planned PFS interim analysis (median follow-up 8.67 vs 8.34 mo), the mPFS was significantly prolonged in the CS1001+chemo arm (stratified HR 0.50 [0.39-0.64], p<.0001; mPFS 7.8 vs 4.9 mo). ORR was 61.4% and 39.2% in CS1001+chemo and placebo+chemo arms, respectively. OS data was immature, but a clinical benefit trend was observed, (stratified HR 0.66 [0.44-0.97]; mOS NR vs 14.75 mo). Subgroup analyses demonstrated clinical benefits across histology and PD-L1 expression levels. Grade 3 TEAEs were reported in 61.9% and 61.6% of pts in CS1001+chemo and placebo+chemo arms, respectively. The 2 arms had similar safety profile, with the exception of mostly Grade 1 and 2 immune-related AEs in CS1001+chemo arm. No new unexpected safety signals were found. Conclusions: This is the first phase III trial conducted in China on an anti-PD-L1 mAb plus chemo that enrolls advanced, treatment-naive sq and nsq NSCLC pts. CS1001 combined with chemo shows statistically significant and clinically meaningful benefit in PFS with a well-tolerated safety profile against chemo across histology and PD-L1 expression levels. It will potentially become a new SOC for 1L treatment of advanced NSCLC once receiving regulatory approval. Clinical trial identification: NCT03789604.

Cancer Research, 2020

Background: IMpower133 (NCT02763579), a global Phase I/III, randomized, double-blind, placebo (PB... more Background: IMpower133 (NCT02763579), a global Phase I/III, randomized, double-blind, placebo (PBO)-controlled trial, showed that the addition of atezo (anti-PD-L1) to CE for 1L ES-SCLC led to statistically and clinically significant OS and PFS improvement vs CE alone. Here we report updated OS and exploratory analyses. Methods: Pts with untreated ES-SCLC were randomized 1:1 to receive four 21-day cycles of E (100 mg/m2 IV, days 1-3) + C (AUC 5 mg/mL/min IV, day 1) with atezo (1200 mg IV, day 1) or PBO, followed by maintenance therapy with atezo or PBO until intolerable toxicity, progression or loss of clinical benefit. PD-L1 testing was not required for enrollment. Coprimary endpoints were investigator-assessed PFS (RECIST 1.1) and OS. Interim and final OS analyses were planned for ≈240 and ≈306 events, respectively. OS was significant at the interim analysis. Updated OS, exploratory biomarkers and patterns of disease progression were analyzed. Results: 201 and 202 pts were randomi...

Cancer Research, 2020

Background: The Ph III IMpower150 study (NCT02366143) showed PFS and OS benefit with atezo + bev ... more Background: The Ph III IMpower150 study (NCT02366143) showed PFS and OS benefit with atezo + bev + carboplatin (carbo) + paclitaxel (pac; ABCP; Arm B) vs bev + carbo + pac (BCP; Arm C) as 1L treatment (tx) for patients (pts) with metastatic nsq NSCLC. Clinical benefit was also seen in pts with EGFR-mutant or ALK-positive (EGFR/ALK+) tumors. We report the final efficacy analyses from IMpower150, including those of the experimental tx arm evaluating atezo + carbo + pac (ACP; Arm A) vs Arm C. Methods: The randomized, open-label, Ph III IMpower150 study evaluated ACP (Arm A) or ABCP (Arm B) vs BCP (Arm C) in pts with metastatic nsq NSCLC (N = 1202). Key eligibility criteria included no prior chemotherapy, measurable disease per RECIST 1.1 and ECOG PS 0-1. Pts were stratified by sex, baseline liver metastases (mets) and PD-L1 expression. Coprimary endpoints were investigator-assessed PFS and OS in ITT wild-type (WT; no EGFR or ALK genetic alterations) pts. Secondary endpoints included PF...

Journal of Clinical Oncology, 2020

9001 Background: Pembro monotherapy showed durable antitumor activity as third-line or later ther... more 9001 Background: Pembro monotherapy showed durable antitumor activity as third-line or later therapy for metastatic SCLC, leading to FDA approval in that setting. KEYNOTE-604 was a double-blind, phase 3 study of pembro + EP vs placebo + EP as first-line therapy for ES-SCLC (NCT03066778). Methods: Eligible patients (pts) with previously untreated ES-SCLC and no untreated CNS metastases were randomized 1:1 to pembro 200 mg Q3W or saline placebo for up to 35 cycles plus 4 cycles of standard-dose EP. Pts with CR or PR after cycle 4 could receive PCI at investigator discretion. Randomization was stratified by platinum choice (carboplatin vs cisplatin), ECOG PS (0 vs 1), and LDH (≤ULN vs > ULN). Primary endpoints were OS and PFS (RECIST v1.1, blinded central review) in the ITT population. ORR, DOR, and safety were secondary endpoints. OS and PFS treatment differences were assessed by the stratified log-rank test. The protocol specified 2 interim analyses (IAs) and a final analysis (FA)...

Journal of Clinical Oncology, 2020

PURPOSE Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung c... more PURPOSE Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung cancer (SCLC). The randomized, double-blind, phase III KEYNOTE-604 study compared pembrolizumab plus etoposide and platinum (EP) with placebo plus EP for patients with previously untreated extensive-stage (ES) SCLC. METHODS Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks or saline placebo for up to 35 cycles plus 4 cycles of EP. Primary end points were progression-free survival (PFS; RECIST version 1.1, blinded central review) and overall survival (OS) in the intention-to-treat population. Objective response rate (ORR) and duration of response were secondary end points. Prespecified efficacy boundaries were one-sided P = .0048 for PFS and .0128 for OS. RESULTS Of the 453 participants, 228 were randomly assigned to pembrolizumab plus EP and 225 to placebo plus EP. Pembrolizumab plus EP significantly improved PFS (hazard ratio [HR], 0.75; 95% CI, 0.61...