Frontline Pembrolizumab or Methotrexate in Elderly, Frail, or Cisplatin-Ineligible Patients with Relapsed or Metastatic Squamous Cell Carcinoma of the Head and Neck: Results of the Randomized Phase 2 Study ELDORANDO (AIO-KHT-0115)
Introduction: Elderly, frail, or cisplatin-ineligible patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) have a poor prognosis. To date, no standard of care has been defined for this population. Methods: The randomized, open-label phase 2 study was conducted to determine whether first-line treatment with pembrolizumab (PEM) is superior to methotrexate (MTX) in elderly, frail, or cisplatin-ineligible patients with R/M HNSCC not amenable to local therapies. Patients were randomized 1:1 to receive PEM 200 mg q3w or MTX 40 mg/m2 IV weekly until disease progression or unacceptable toxicity. The primary end point was overall survival after 1 year (1YOS); secondary endpoints were time to failure of strategy (TTFS) at 1 year, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 100 planned participants, 47 (23 in the PEM and 24 in the MTX group) were enrolled. The trial was terminated prematurely. Efficacy did not differ between the treatment arms (1YOS 17.4% for PEM vs. 37.5% for MTX [p = 0.12]). ORR was 17.4% with PEM vs. 12.5% with MTX (p = 0.70), TTFS at 1 year was 91% vs. 100% (p = 0.47), median PFS was 1.8 vs. 2.7 months (p = 0.83), and median OS was 6.1 vs. 9.7 months (p = 0.50), respectively. PD-L1 expression did not impact primary and secondary endpoints. Safety parameters favored PEM. Conclusion: ELDORANDO failed to demonstrate benefit of PEM over MTX regarding 1YOS, ORR, PFS, or OS. The optimal treatment strategy for fragile patients remains to be determined.
- Research Article
1
- 10.1200/jco.2019.37.15_suppl.3559
- May 20, 2019
- Journal of Clinical Oncology
3559 Background: XELAVIRI compared initial vs sequential irinotecan (iri) in combination with fluoropyrimidine (FP) plus bevacizumab (bev) in patients (pts) with mCRC, trial identification: NCT01249638. In the full analysis set of the study, non-inferiority of time to failure of strategy (TFS) was not shown (primary endpoint). Pts with RAS/BRAF wildtype (wt) tumors benefitted from initial iri. Methods: The study endpoints objective response rate (ORR), progression-free survival (PFS), time to failure of strategy (TFS) as well as overall survival (OS) were evaluated in female vs. male pts as well as molecular subgroups (i.e. RAS mutational status). Interaction of treatment and gender was tested by likelihood ratio tests. Results: Of 421 patients, 281/140 were male/female. In male patients, ORR was 33.6% without and 58.3% with initial iri (P < 0.001). PFS (HR: 0.54 (95%CI 0.42-0.69) P < 0.001) and OS (HR: 0.63 (95%CI 0.47-0.85), P = 0.002), were also significantly better with initial iri. In the subgroup analysis, this effect was especially pronounced in pts with RAS/BRAF wt tumors. In female pts, ORR was 43% in both arms, PFS was similar (HR: 1.09 (95%CI 0.76-1.55), P = 0.65) without and with initial iri. In OS, a strong trend for inferior outcome with initial iri was seen (HR: 1.46 (95%CI 0.95-2.24), P = 0.08) that reached significance in the multivariate analysis (HR: 1.73 (95%CI 1.04-2.86, P = 0.034). Female patients with RAS/BRAF wt tumors did not benefit from initial iri (HR 1.05 (95% CI 0.46-2.41), P = 0.903 for OS). Formal interaction of treatment and gender was seen for ORR (P = 0.018), PFS (P = 0.002) and OS (P = 0.001). There were some trends for more pronounced toxicities in female pts treated with Irinotecan. Conclusions: This unplanned exploratory analysis suggests that gender might interact with efficacy of initial iri when used in the context of FP and bev. While especially male RAS wild-type patients derived a significant and clinically meaningful benefit from initial use of iri, this was not observed in female patients with RAS wt tumors. Clinical trial information: NCT01249638.
- Research Article
8
- 10.1136/esmoopen-2018-000399
- Nov 1, 2018
- ESMO Open
BackgroundEpidermal growth factor receptor (EGFR) is one of the most common oncogenes in non-small cell lung cancer (NSCLC). EGFR-tyrosine kinase inhibitor (TKI) and platinum-doublet chemotherapy (PT) are effective regimens in patients with NSCLC harbouring EGFR mutations. Among these patients, progression-free survival (PFS) has been used as a surrogate endpoint; however, it may not correlate with overall survival (OS) due to crossover. Time to failure of strategy (TFS) has been proposed as an alternative endpoint in advanced colorectal cancer clinical trials where multiple effective therapies are provided either in combination or sequentially. Nevertheless, it remains unclear whether TFS is useful in lung cancer trials.Patients and methodsWe retrospectively reviewed patients with NSCLC harbouring EGFR mutations who chose a treatment strategy consisting of EGFR-TKI and PT as the initial two regimens at the National Cancer Center Hospital. We evaluated the relationship between PFS and OS and between TFS and OS.ResultsBetween May 2005 and April 2015, a total of 374 patients were diagnosed with NSCLC harbouring EGFR mutations. Among them, 158 patients were eligible for analysis. The median PFS, TFS and OS of the patients were 11.2 months (95% CI 9.9 to 12.6), 21.3 months (95% CI 18.6 to 26.2) and 36.6 months (95% CI 32.0 to 41.8), respectively. OS and TFS, but not PFS, were better in patients who received PT then EGFR-TKI compared with those who received the opposite schedule. The non-parametric Spearman’s rank correlation coefficients (r) between PFS and OS and between TFS and OS were 0.54 and 0.85, respectively.ConclusionsThis is the first report describing TFS data among patients with NSCLC with EGFR mutations who received EGFR-TKI and PT as the initial two regimens. TFS was acceptable as a surrogate endpoint for OS. Further validation in clinical trials is needed.
- Abstract
- 10.1093/annonc/mdw370.143
- Oct 1, 2016
- Annals of Oncology
595P - Correlation between alternative endpoints and overall survival in metastatic colorectal cancer patients eligible to a maintenance strategy
- Front Matter
31
- 10.1016/j.annonc.2021.03.208
- Apr 8, 2021
- Annals of Oncology
How low can you go? PD-L1 expression as a biomarker in trials of cancer immunotherapy
- Research Article
- 10.1200/jco.2024.42.16_suppl.3506
- Jun 1, 2024
- Journal of Clinical Oncology
3506 Background: The randomized open-label phase II PanaMa trial compared FU/FA with or without pmab maintenance after mFOLFOX6+pmab induction for RAS wild-type mCRC. Updated efficacy results of the Full Analysis Set are presented. Methods: Median progression-free survival (PFS), overall survival (OS), PFS of re-induction (PFS re-ind.), time to failure of strategy (TFS), and objective response rates (ORR) were compared by log-rank test / Cox regression and Fisher’s exact test. Results: PFS was significantly (8.8 vs. 5.8 months, HR=0.73 (95%CI 0.56 – 0.94), P=0.015) and OS numerically longer (29.9 vs. 24.7 months, HR=0.85 (95%CI 0.64 – 1.12), P=0.24). PFS re-ind. was significantly shorter after pmab maintenance (4.1 vs. 7.4 months, HR=1.93 (95%CI 1.33 – 2.82), P<0.001). TFS was comparable (17.1 vs. 15.7 months, HR=0.98 (95%CI 0.68 – 1.42), P=0.92). Molecular subgroups are displayed in Table 1. ORR of FU/FA+pmab was comparable to FU/FA during induction (74.4% vs. 76.4%, P=0.77), higher during maintenance (40.8% vs. 29.3%, P=0.06), but lower at re-induction (8.0% vs. 35.9%, P<0.001). Conclusions: PFS remained improved by the addition of pmab to FU/FA maintenance therapy, while OS was not significantly longer. Re-induction of pmab+mFOLFOX6 did not provide benefit following pmab maintenance regarding PFS. Clinical trial information: NCT01991873 . [Table: see text]
- Abstract
1
- 10.1182/blood-2024-199733
- Nov 5, 2024
- Blood
Linvoseltamab in Patients with Relapsed/Refractory Multiple Myeloma: Longer Follow-up and Selected High-Risk Subgroup Analyses of the Linker-MM1 Study
- Research Article
8
- 10.1200/jco.2021.39.15_suppl.6070
- May 20, 2021
- Journal of Clinical Oncology
6070 Background: Lenvatinib is now available for unresectable radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). However, toxicities are considerable and require frequent dose interruption and modification. Recently, planned drug holidays, which are dose interruptions in accordance with the timing of severe or intolerable adverse events, have been proposed to avoid severe adverse events due to lenvatinib (Tahara M.ESMO Open 2018). Our retrospective study demonstrated that progression-free survival (PFS) and overall survival (OS) were significantly longer in patients who used planned drug holidays than those who did not (Matsuyama C et.al, 2020 Annual Meeting of the Japan Association of Endocrine Surgeons). Methods: In this prospective observational study, patients with curatively unresectable and progressive RAI-refractory DTC were treated with lenvatinib in a real-world clinical setting. Lenvatinib was administered orally at a dose of 24 mg daily. Dose modification for toxicities were permitted. Primary endpoint was OS, and secondary endpoints were time to treatment failure (TTF), time to failure of strategy (TFS), PFS with clinical progressive disease, response rate, quality of life, safety, and patient reports. This study was registered with UMIN Clinical Trials Registry (UMIN000022243). Results: 262 patients were accrued. Of 255 evaluable, 153 were female; median age was 70 (range 27.0-88.0); histology was papillary thyroid carcinoma/follicular thyroid carcinoma/poorly DTC in 204/45/4; previous therapy was surgery/RAI/molecular targeted drug in 246/164/14; reason for initiation of lenvatinib was disease progression/unsuitable for RAI in 241/4. 1-year OS was 85.6% (95%CI: 80.6-89.4%); 1-year TTF rate was 74.9% (95%CI: 69.1-79.8%); 1-year TFS rate was 80.8% (95%CI: 75.4-85.2%); and 1-year PFS rate was 84.4% (95%CI: 79.3-88.4%). Overall response by RECIST was 3 (1.2%) in CR and 151 (61.9%) in PR. Most common grade 3 or 4 toxicities were hypertension (61.4%), hand foot syndrome (10.2%), fatigue (9.1%), anorexia (8.3%) and diarrhea (4.7%). Grade 5 toxicities occurred in 4 patients (fistula, hypoxia, respiratory failure, trachea stenosis). Of 253 patients evaluable for efficacy, 73 used planned drug holidays. TTF, TFS and PFS were significantly longer in patients who used planned drug holiday than those who did not (Table). Conclusions: Planned drug holiday for lenvatinib demonstrated significantly better clinical outcomes, including TTF, TFS and PFS, than daily oral administration. These data further support use of a planned drug holiday in RAI-refractory DTC patients receiving lenvatinib. Clinical trial information: 000022243. [Table: see text]
- Research Article
2
- 10.1016/j.clcc.2017.10.001
- Oct 19, 2017
- Clinical Colorectal Cancer
Clinical Relevance of Alternative Endpoints in Colorectal Cancer First-Line Therapy With Bevacizumab: A Retrospective Study
- Research Article
8
- 10.1200/jco.2022.40.4_suppl.444
- Feb 1, 2022
- Journal of Clinical Oncology
444 Background: Immune checkpoint inhibitors (ICI) have limited activity as monotherapy in unselected patients with ABC; the objective response rate (ORR) of PEM was 5.8% in the multicenter phase 2 KEYNOTE-158 trial. GM-CSF modulates immune cells including monocytes and the innate immune response and has demonstrated safety and prolonged survival (OS) in combination with ipilimumab in melanoma. This phase 2 trial was designed to evaluate the efficacy and safety of PEM in combination with GM-CSF in ABC. Methods: Single-center, phase 2 trial with Simon’s 2-stage design and expansion cohort (EC) (NCT02703714). Key eligibility: ABC with progression/intolerance on ≥ 1 standard therapy, no prior ICI, bilirubin ≤1.5xULN. Treatment: PEM 200 mg IV Q21 days plus 2 cycles of GM-CSF 250 µg SC D1-14 Q21 days in cycles 2 and 3 (Stage 1 and EC) or in cycles 1 and 2 (Stage 2). Primary endpoint was objective response rate (ORR) by RECIST 1.1, H0 5% vs. H1 20%. Key secondary endpoints were safety, progression-free survival (PFS), OS, PD-L1 expression. Exploratory endpoints included relationship between efficacy outcomes and anatomic subsite, risk factors, and tumor genotype. Results: Overall, 42 patients enrolled between 5/2016-12/2019: n = 9 in Stage 1, n = 18 in Stage 2, and n = 15 in EC. Overall: median age 61; female 67%; intrahepatic (ICC) 67%, extrahepatic (ECC) 26%, gallbladder (GBC) 7%; stage IV 90%; hepatitis B/C virus positive (HBV/HCV+) 24%; microsatellite instability (MSI-H)/stable (MSS)/unknown n = 1/35/6. Immune-related (ir)AE occurred in 69%, grade 3/4 treatment-related (tr)AE in 10%, all-cause serious (S)AE in 36%, and trSAE in 7%. ORR was 12% (95% CI: 4, 26), with median PFS of 63 days (95% CI: 55, 125), PFS at 6 months in 27% (95% CI: 14, 43), and median OS 3of 93 days (95% CI: 243, 573). There was no significant difference in ORR, PFS, or OS by anatomic subsite or tumor PD-L1 expression; HBV/HCV+ showed trends toward higher ORR (30% vs 6%, p = 0.08) and longer median PFS (276 vs 63 days, p = 0.06) and OS (1033 vs 323 days, p = 0.052). Conclusions: The combination of PEM plus GM-CSF was safe and well-tolerated with higher ORR than expected for PEM monotherapy in a predominantly MSS ABC population but did not meet target ORR threshold for efficacy. ORR and median PFS and OS were highest in patients with underlying HBV or HCV infection. Immune profiling of on-treatment biopsies and peripheral blood are ongoing to ascertain influence of both PEM and GM-CSF on circulating and tumor immune microenvironment. Clinical trial information: NCT02703714.
- Research Article
2
- 10.1200/jco.2009.27.15_suppl.4073
- May 20, 2009
- Journal of Clinical Oncology
4073 Background: Progression-free survival (PFS) is not an optimal endpoint in therapeutic strategies evaluating either stop and go or alternated therapies, or a fixed sequence of two therapies. DDC (Tournigand, JCO 2006) and TFS (Allegra, JCO 2007) composite endpoints have been proposed to evaluate efficacy of these strategies in ACC. This study compared these two alternative endpoints. Methods: DDC is defined as the sum of the PFS of each sequence, except when progressive disease is observed at either reintroduction or second-therapy (DDC=PFS1+PFS2 if treatment 2 achieved stabilization or response). TFS is defined as the total PFS from the initiation of the strategy to disease progression while on all the planned agents, or disease progression during a treatment-free interval and no further therapy received within 1 month, or death (TFS=PFS 1+2). Both DDC and TFS have been calculated in three trials: OPTIMOX1 (oxaliplatin stop and go vs continuous administration, updated database, Tournigand, JCO 2006), OPTIMOX2 (oxaliplatin stop and go vs complete stop and go, updated database, Maindrault-Goebel, ASCO 2007) and C97–3 (FOLFIRI1- FOLFOX6 or reverse sequence, Tournigand 2004). Results: The median potential follow-up time was 39.8 months. There was a moderately shorter DDC than TFS in the two stop and go studies, but a much shorter DDC than TFS in the sequential therapy study. There was a significant correlation between DDC and OS (r=0.96, p=.002) but not between TFS and OS (r=0.71, p=.11) Conclusions: Two bias impacted TFS 1) the results of resuming the planned therapeutic strategy for progression after a chemotherapy-free interval of more than one month was not considered, 2) patients who were not progressive at the end of planned strategy could not be censored at that time. The shorter duration of DDC over TFS may have an advantage in terms of sample size for evaluation of therapeutic strategies. In case of drug registration, DDC does not increase in case of inactive second sequence. [Table: see text] No significant financial relationships to disclose.
- Research Article
9
- 10.1016/j.cllc.2022.09.002
- Sep 17, 2022
- Clinical Lung Cancer
Brief Report: First-line Pembrolizumab in Metastatic Non-Small Cell Lung Cancer Habouring MET Exon 14 Skipping Mutation and PD-L1 ≥50% (GFPC 01-20 Study)
- Research Article
- 10.1200/jco.2023.41.16_suppl.e21044
- Jun 1, 2023
- Journal of Clinical Oncology
e21044 Background: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic drugs may have synergistic effects in elderly patients with advanced driver-gene wild-type non-small cell lung cancer (NSCLC), but its true efficacy remains unclear. In addition, the chemotherapy tolerance of elderly NSCLC patients is poor, and the precise identification of the population who can benefit from ICIs combined with angiogenesis inhibitors is also the focus of current research. Methods: We retrospectively compared the clinical efficacy and safety of ICIs combined with or without antiangiogenic agents in elderly patients with advanced driver-gene negative NSCLC who were ≥65 years old in the Cancer Center of the Affiliated Suzhou Hospital of Nanjing Medical University. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs). Results: A total of 36 patients in the IA group(Immune checkpoint inhibitors plus angiogenesis inhibitors group) and 43 patients in the NIA group(Immune checkpoint inhibitors without angiogenesis inhibitors group) were enrolled in the study between January 1, 2019 and December 31, 2021. The median follow-up time for patients in IA group and NIA group was 18.2 months (95%CI: 14 - 22.5 months) and 21.4 months (95%CI: 16.7 -26.1 months), respectively. The median PFS and median OS were longer in the IA group compared to the NIA group(8.1 months vs 5.3 months;HR for PFS: 0.778, 95%CI: 0.474-1.276, P = 0.32; NA vs 30.9 months; HR for OS: 0.795, 95%CI: 0.396-1.595, P = 0.519). Subgroup analysis showed that patients in the IA group had significantly longer PFS in the subgroup with PD-L1 expression ≥50% (P = 0.017), and the relationship between treatment regimens and outcomes was still discrepant in different PD-L1 expression levels (P for interaction = 0.002). There was no significant difference in ORR between the two groups (23.3% vs 30.5%, P = 0.465). The incidence of adverse events in IA group was lower than that in NIA group (39.5% vs 19.4%, P = 0.05), and the cumulative incidence of treatment interruptions due to adverse events was significantly reduced (P = 0.045). Conclusions: In elderly patients with advanced driver-gene wild-type NSCLC, the addition of antiangiogenic agents to ICIs therapy did not provide significant clinical benefit, but the incidence of treatment interruptions due to adverse events was significantly reduced. In the subgroup analysis, we found that the clinical benefit of this combination therapy was observed in patients with PD-L1 expression ≥50%, which warrants further exploration. Clinical trial information: NCT05688046 .
- Research Article
1
- 10.1097/hc9.0000000000000117
- Jun 1, 2023
- Hepatology communications
Evolution of systemic therapy for advanced HCC patients: Did we make progress in 2022?
- Research Article
4
- 10.1200/jco.2025.43.16_suppl.8500
- Jun 1, 2025
- Journal of Clinical Oncology
8500 Background: In the phase 2 KRYSTAL-7 study (NCT04613596), first-line ADA, a KRAS G12C inhibitor, plus PEMBRO demonstrated clinical activity and a manageable safety profile in pts with advanced/metastatic KRAS G12C -mutated NSCLC and PD-L1 ≥50% (Garassino et al. Ann Oncol 2023). Here we report efficacy and safety data, including the first disclosure of survival data, for pts across all PD-L1 tumor expression levels. Methods: Pts with advanced/metastatic KRAS G12C -mutated NSCLC and known PD-L1 tumor proportion score received first-line ADA (400 mg orally BID) plus PEMBRO (200 mg IV Q3W). The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DOR) and progression-free survival (PFS) assessed by investigator, overall survival (OS), and safety. Results: As of August 23, 2024, 149 pts had received ADA plus PEMBRO (median OS follow-up 22.8 mo): median age was 67 years, 48% were female, and 62% had ECOG PS 1. ORR was 44.3% (95% CI 36.2–52.7); median DOR was 26.3 mo (95% CI 14.9–not estimable [NE]); median PFS was 11.0 mo (95% CI 5.8–14.0) with an 18-mo PFS rate of 37.6% (95% CI 29.0–46.1); and median OS was 18.3 mo (95% CI 14.3–NE) with an 18-mo OS rate of 51.8% (95% CI 43.0–59.8). Efficacy outcomes per PD-L1 status are shown in the Table. Treatment-related adverse events (TRAEs) of any grade (G) were reported in 94.6% of pts (G3/4 in 68.4%); three G5 TRAEs were reported (pneumonia [n=2]; pneumonitis [n=1]). The most common hepatic TRAEs (any G) were increases in alanine aminotransferase (39.6%; G3/4 in 11.4%), aspartate aminotransferase (35.6%; G3/4 in 14.1%), and alkaline phosphatase (19.5%; G3/4 in 6.7%). The discontinuation rate due to hepatic TRAEs was 2.0% for ADA, 6.7% for PEMBRO, and 0.7% for both ADA and PEMBRO. Conclusions: In pts with advanced/metastatic KRAS G12C -mutated NSCLC, first-line ADA plus PEMBRO demonstrated promising clinical efficacy and a manageable safety profile, regardless of PD-L1 status. These data represent the largest dataset evaluating a first-line KRAS G12C inhibitor plus PD-(L)1 inhibitor in this population presented to date. The phase 3 portion of KRYSTAL-7, comparing first-line ADA plus PEMBRO vs PEMBRO monotherapy in pts with KRAS G12C -mutated NSCLC and PD-L1 ≥50%, is ongoing and recruiting. Clinical trial information: NCT04613596 . PD-L1 <50%(n=95) PD-L1 ≥50%(n=54) ORR, n (%)95% CI 34 (35.8)26.2–46.3 32 (59.3)45.0–72.4 Median DOR, mo (95% CI) (n=34)18.2 (11.1–NE) (n=32)26.3 (26.3–NE) Median PFS a , mo (95% CI)18-mo rate, % (95% CI) 6.9 (3.9–12.4)29.8 (19.8–40.4) 27.7 (8.1–NE)50.7 (35.5–64.0) Median OS b , mo (95% CI)18-mo rate, % (95% CI) 15.5 (11.1–21.0)45.2 (34.3–55.6) NE (15.4–NE)62.4 (47.5–74.1) a Median PFS follow-up 17.5 mo (PD-L1 <50%) and 22.6 mo (PD-L1 ≥50%); b Median OS follow-up 21.4 mo (PD-L1 <50%) and 24.9 mo (PD-L1 ≥50%).
- Research Article
1
- 10.1200/jco.2017.35.15_suppl.9049
- May 20, 2017
- Journal of Clinical Oncology
9049 Background: Correlations between overall survival (OS) and objective response rate (ORR) or progression-free survival (PFS) are poor. We aimed to evaluate the impact of crossover and unbalanced subsequent treatments on ORR and PFS as surrogate endpoints for OS in patients with advanced NSCLC receiving first-line therapy. Methods: A systematic literature review of randomized clinical trials of systemic treatment for patients with stage IIIB/IV NSCLC receiving first-line therapy was performed. Weighted (by trial size) linear regression models were fitted with the absolute difference in ORR or median PFS as an independent variable and the absolute difference in median OS as a dependent variable. The analysis was repeated in predefined subsets based on crossover and balance of post-progression therapies. Surrogate threshold effect (STE) was estimated using prediction intervals. Results: 317 trials (78,644 patients) fulfilled the eligibility criteria. In all treatment arms, the mean ORR, median PFS, and median OS were 28.2% (standard deviation (SD) = 12.4%), 5.1 months (SD = 2.1), and 10.4 months (SD = 2.5), respectively. ORR and PFS had weak (R = 0.351; 95% CI: 0.251-0.443) and (R = 0.397; 95% CI: 0.267-0.512) associations with OS, respectively. However, within phase III trials that did not allow crossover and reported balanced post-progression treatments, both ORR and PFS had stronger associations with OS (ORR and OS: R = 0.601, 95% CI: 0.399-0.747; PFS and OS: R = 0.695, 95% CI: 0.446-0.844). STE estimation indicated that trials that show statistically significant treatment effect size of ≥43% ORR or ≥3.2 median PFS months can be expected to show significant OS benefit with sufficient certainty. Conclusions: Surrogacy of ORR and PFS for OS might be better estimated in trials that do not allow crossover and report balanced post-progression treatments. Presented STE calculation can be used to estimate the expected effect on OS when either ORR or PFS are used as primary endpoints.
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