Patterns and management of progression on first-line ipilimumab combined with anti-PD-1 (IPI+PD1) in metastatic melanoma (MM) patients.

9533 Background: First line IPI+PD1 induces long-term response in 36% of MM patients (pts); however, the majority of pts will progress and may require further treatment, which is yet to be established. We studied the patterns of progressive disease (PD) on 1st line IPI+PD1, and the management and outcomes in MM pts. Methods: Demographics, disease characteristics, nature of PD, subsequent treatments and outcomes were examined in MM pts with PD on 1st line IPI+PD1. Multivariable analyses (MVA) identified factors associated with patterns of PD: innate resistance (IR) = PD as best response or stable disease (SD) < 6 mo; acquired resistance (AR) = PD after initial response or SD ≥ 6 mo. Results: 310 MM pts from 14 melanoma centres were included; 208 (67%) had PD during and 102 (33%) after ceasing IPI+PD1. Overall med. progression-free survival (mPFS) was 2.8 mo (CI 95% 2.7 – 3.0); 187 pts (60%) had IR (mPFS 2.2 [2.1 – 2.5]), 112 pts (36%) had AR (mPFS 8.5 [7.2 – 10.2]) and 11 pts (4%) had pseudoprogression, i.e. PD followed by response without changing treatment (mPFS 2.7 mo [1.4 – NA]). On MVA, pts with ECOG PS ≥ 1 were more likely to have IR vs AR; and within IR pts, those with head & neck primary melanomas and lung metastases were more likely to have PD < 1.5 mo. Most pts with IR (68%) had PD in multiple sites, while 61% AR pts had PD in a single site. Brain was most common site of single organ PD; 49% of IR and 41% of AR. Med. follow-up from PD was 32.7 mo (28.1 – 36.8). After PD, 61 pts (20%) had best supportive care (26% of IR and 11% of AR pts). 259 pts (80%) received further treatment: 39% IR pts had systemic treatment (ST) only and 27% had ST + local; 31% AR pts had ST only and 39% had ST + local. Of 200 pts (65%) who had ST(+/-local), 54% had 1 line of ST and 46% had ≥ 2; 1st line ST (ST1) was BRAF/MEKi in 36% of pts, PD1 in 32%, IPI+PD1 in 7%, investigational drugs in 11%, chemotherapy in 9% and others in 5%. ORR in IR pts was lower than in AR pts for every type of ST1 (see Table). Med. OS from PD was 11.4 mo (CI 95% 9.6 – 16.1); IR 6.4 mo (CI 95% 5.6 – 10.2) and AR 26.1 mo (CI 95% 17.1 – NA). Conclusions: These data suggest longer OS from PD for AR vs IR pts independent of ST type. BRAF/MEKi, rechallenge with PD1+/-IPI and investigational drugs showed activity after PD on IPI+PD1, while chemotherapy has no role in this context.[Table: see text]

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Clinical outcomes of metastatic renal carcinoma following disease progression to programmed death (PD)-1 or PD-L1 inhibitors (I-O): A Meet-URO group real-world study (Meet-Uro 7).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.691 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 691-691

Author(s):

Daniele Santini ◽

Marco Stellato ◽

Ugo De Giorgi ◽

Sandro Pignata ◽

Francesco Pantano ◽

...

Keyword(s):

Adverse Events ◽

Real World ◽

Progression Free Survival ◽

Mtor Inhibitors ◽

Outcome Data ◽

First Line ◽

Real World Data ◽

Best Response ◽

Ecog Ps ◽

Immune Oncology

691 Background: In metastatic renal cell carcinoma (mRCC), immune-oncology (IO), alone or in combination, (IO-IO or IO-TKI) has changed the therapeutic scenario. Few real-world data are available about safety and outcome after IO progression. Methods: Baseline characteristics, outcome data including progression-free survival (PFS) and toxicities were retrospectively collected from 162 eligible pts treated in 16 Italian referral centers adhering to the Meet-Uro group and progressing to IO. Results: 111 pts (68,5%) were treated after progression to IO. 142 (87.6%) pts received IO as second line, 5 pts as first line and 16 pts as further line. Subsequent therapy included cabozantinib (n = 79, 48.0%), everolimus (n = 11, 6.7%), sunitinib (n = 6, 3.7%) and others (n = 15, 9.25%). Median IO-PFS was 4 months (95%CI 3.1-4.8) with no difference in pts pretreated with pazopanib or sunitinib (4 months (95%CI 2.4-5.5) vs 3,9 months (95%CI 2.9-4.9) p = 0.5). PFS tends to be longer in pts reporting adverse events of any grade (5.03 (95%CI 3.8-6.1) vs 2,99 (95%CI 2.4-3.5) months p = 0.004) or without nephrectomy (4.1 vs 2.9 months p = 0.071). Median PFS, in pts treated post-IO, was 6.5 months (95%CI 5.1-7.8). In term of best response, 55 pts (49%) had stability of disease/partial response and 29 pts (26%) had progressive disease, for the other pts treatment is still ongoing. Pts with ECOG PS 0 at progression to IO, had longer PFS, 11 months (95%CI 5.7-17.5) as well as those treated with cabozantinib (7.6 months, 95%CI 5.2-10.1) compared to everolimus, (3.2 months, 95%CI 1.8-4.5) or other drugs (4.3 months, 95%CI 1.3-7.4) p = 0.001. All grade adverse events were reported in 83 pts (74%) with G3-G4 adverse events in 39 pts (35%). Median overall survival, from first line, was 41,1 months (95%CI 30.4-51.8). Conclusions: In our real world experience after progression to IO, most pts received VEGF-TKI and mTOR inhibitors that showed to be active and safe choices. Cabozantinib was associated with a longer mPFS.

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Retrospective Comparative Analysis of KRAS G12C vs. Other KRAS Mutations in mCRC Patients Treated With First-Line Chemotherapy Doublet + Bevacizumab

Frontiers in Oncology ◽

10.3389/fonc.2021.736104 ◽

2021 ◽

Vol 11 ◽

Author(s):

Riccardo Giampieri ◽

Alessio Lupi ◽

Pina Ziranu ◽

Alessandro Bittoni ◽

Andrea Pretta ◽

...

Keyword(s):

Metastatic Disease ◽

Progression Free Survival ◽

Response Rates ◽

The Other ◽

First Line ◽

Kras Mutations ◽

Other Hand ◽

Best Response ◽

The Difference ◽

Ecog Ps

BackgroundKRAS mutations in metastatic colorectal cancer (mCRC) define a subset of tumors that have primary resistance to anti-EGFR-based therapy. Data concerning whether different KRAS mutations may also have a prognostic value are lacking. Furthermore, novel KRAS G12C inhibitors are currently in development. The aim of our analysis was to compare response rates in patients treated with first-line chemotherapy doublet + Bevacizumab among different KRAS variants. Secondary end-points were progression free survival (PFS) and overall survival (OS).MethodsPatients with KRAS mutated mCRC treated with either FOLFIRI/FOLFOX/XELOX + Bevacizumab were eligible for enrollment. Patients whose tumor harbored NRAS mutations or that coexpressed also BRAF mutations were excluded from this retrospective analysis. Patients’ individual data were collected from patients’ records. Propensity score matching (nearest method, 1:2 ratio) was used to define the two different groups of patients for comparison (KRAS G12C mutated vs other KRAS variants). Eastern Cooperative Oncology Group Performance Status (ECOG PS), sex, metastatic site of involvement, synchronous vs metachronous metastatic disease, tumor sidedness, mucinous histology, primary tumor surgery, more than two lines of treatment for metastatic disease, and radical surgery of metastases were used as matching factors. Response rate (RR) was calculated by RECIST 1.1 criteria. Both progression free-survival and overall survival were calculated by Kaplan–Meier method. Categorical variables were compared by Fisher exact test for binomial variables and by chi-square test for all other instances. The level of statistical significance p was set at 0.05 for all tests.ResultsA total of 120 patients were assessed in the final analysis. Out of the 120 patients, 15 (12%) were KRAS G12C mutated. In the whole cohort of patients, 59/120 (49%) had partial response (PR), 42/120 (35%) had stable disease (SD), and 19/120 (16%) had progressive disease (PD) as the best response. In KRAS G12C patients, 4/15 (27%) had PR, 6/15 (40%) had SD, and the remaining 5/15 (33%) had PD as the best response. In patients with other KRAS mutations, 55/105 (52%) had PR, 37/105 (35%) had SD, and the remaining 13/105 (12%) had PD as the best response. The difference in RR between the two groups of patients was statistically significant (p=0.017). On the other hand, no difference in PFS (p=0.76) and OS (p=0.56) was observed. After matching procedures, the difference in response rates between KRAS G12C mutated patients vs the matched cohort of patients with other KRAS mutations remained statistically significant (p=0.016). KRAS G12C mutations were not associated with differences in sites of metastatic involvement, sex, and ECOG PS. On the other hand, synchronous vs metachronous metastatic disease (p=0.039), age > 75 years (p=0.043), and mucinous histology (p=0.008) were more frequent in G12C mutated tumors.ConclusionsIn our cohort of patients, it was observed that KRAS G12C mutations are associated with worse response rates compared to other KRAS variants when treated with standard chemotherapy doublet + Bevacizumab. On the other hand, both PFS and OS were not significantly different. Based on these findings, we believe that new treatment options focused on KRAS G12C inhibition should be tested mainly in first-line setting and in addition to standard chemotherapy doublet + Bevacizumab for mCRC patients, as they might “fill the gap” in response rates that was seen in our study.

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Rarity of acquired mutations (MTs) after first-line therapy with anti-EGFR therapy (EGFRi).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3514 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3514-3514

Author(s):

Christine Megerdichian Parseghian ◽

Ryan Sun ◽

Stefania Napolitano ◽

Van K. Morris ◽

Jason Henry ◽

...

Keyword(s):

Clonal Evolution ◽

Acquired Resistance ◽

Best Supportive Care ◽

Plasma Samples ◽

Resistance Mutations ◽

First Line ◽

First Line Therapy ◽

Best Response ◽

Ctdna Analysis ◽

Line Setting

3514 Background: Colorectal cancers (CRC) lacking RAS MTs treated with EGFRi are thought to evolve by a repetitive process of genetic diversification and clonal evolution. Acquired MTs in KRAS, NRAS, BRAF, MAP2K1, and EGFR are known mechanisms of acquired resistance in the EGFRi refractory population. However, the prevalence of MTs in the first line (1L) setting is not well established as most experience with EGFRi has been beyond the 1L setting. Methods: We analyzed paired plasma samples from RAS/BRAF/EGFRWT mCRC patients (pts) enrolled in 3 large randomized phase 3 trials who had been treated with EGFRi and in whom paired baseline (BL) and time of progression (PRO) plasma samples had been collected for sequencing of ctDNA on a platform optimized for very low allele frequencies (Plasma Select-R™ and Resolution Bio™). Prevalence of MTs at BL and PRO from a 1L study (‘203; FOLFOX ± panitumumab) were compared with 2 studies in the third line setting (3L; ‘007; panitumumab + best supportive care [BSC] vs BSC; and 3L; ‘763; panitumumab vs. cetuximab), to assess the frequency of acquired resistance mutations via ctDNA analysis. Results: For pts with available paired plasma samples (n = 112 for ‘203; n = 89 for ‘007; n = 274 for ‘763), acquisition of at least one KRAS, NRAS, BRAF, MAP2K1, or EGFR MT was significantly less common in post-progression samples in the EGFR containing arms of the 1L ‘203 study compared to the 3L ‘763 and ‘007 studies (6.8% vs 50.4% vs 39.6%, respectively; p < 0.001). In the non EGFR containing arms of the ‘203 and ‘007 study, the rate of acquired MTs was 7.5% and 0%, respectively (p = 1). While this difference in the rate of acquired MTs between the EGFR and non EGFR containing arms was statistically significant for the 3L study (p < 0.001) it was not significant for the 1L study. Further, pts on both 3L studies treated with EGFRi who experienced CR, PR or SD acquired more MTs than those who had PD as best response (53.6% vs 33.3%, respectively; p < 0.001). This relationship was not significant in the 1L setting (7.7% vs 0%; p = 1). Subclonal MTs (rMAF < 25%) in KRAS, NRAS, EGFR, BRAF and MAP2K1 were present at BL in 129 pts (27%). Based on the hypothesis that EGFRi is selecting for rare existing mutated cells in the tumor, we would expect expansion of any preexisting subclones in the BL samples. However, in contrast to expectations, these subclones rarely expanded to become clonal at the time of progression (12.4%). Conclusions: In contrast to expectations, acquired KRAS, NRAS, BRAF, EGFR, or MAP2K1 MTs rarely develop after 1L therapy. While selective pressure appears to increase the frequency of acquired MTs in the 3L setting, preexisting subclonal MTs do not appear to be the dominant source of acquired MTs at progression, implying that there may also be a transient mutational process driving resistance rather than expansion of preexisting clones. These findings have significant implications for ongoing and planned EGFRi rechallenge studies.

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Durability of response to immune checkpoint inhibitors (ICI) in metastatic Merkel cell carcinoma (mMCC) after treatment cessation.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9543 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9543-9543

Author(s):

Alison Margaret Weppler ◽

Laetitia Da Meda ◽

Ines Silva ◽

Wen Xu ◽

Giovanni Grignani ◽

...

Keyword(s):

Median Time ◽

Checkpoint Inhibitors ◽

Initial Response ◽

Leptomeningeal Disease ◽

Treatment Cessation ◽

Cns Involvement ◽

Duration Of Treatment ◽

Disease Characteristics ◽

Best Response

9543 Background: mMCC is a rare, aggressive neuroendocrine cancer which often occurs in older patients (pts) with multiple comorbidities. While initial response rates to ICI are high, optimal treatment duration, durability of response after treatment cessation and response to retreatment with ICI is unknown. Methods: mMCC pts from 12 international centres who received at least one dose of ICI and subsequently stopped treatment without progression for a minimum of 12 weeks were studied. Demographics, disease characteristics and treatment course were examined. Results: 40 pts with mMCC were included. Pt characteristics are summarised in Table. Median time on treatment was 13.5 months (range 1 to 35). Median time to best response was 4.5 months (range 1 to 17) and median time receiving treatment after best response was 8 months (range 0 to 29). 25 pts (63%) stopped primarily due to being in a complete or partial response (CR or PR), 9 (23%) due to toxicity and 6 (15%) due to other reasons, primarily pt choice or comorbidities. At time of discontinuation, 30 pts (75%) were in a CR, 8 (20%) in a PR and 2 pts (5%) had stable disease (SD). After a median follow up of 12 months from discontinuation, 14 pts (35%) have progressed (PD); 5 (36%) at a previous site, 5 (36%) at a new site and 4 (29%) at both. PD occurred after a median of 5.5 months (range 4 to 29) off treatment. 4 pts (29%) had a CNS recurrence, none of whom previously had CNS involvement. Pts in CR at time of discontinuation were less likely to progress (CR: 26% PD vs non-CR: 67% PD, p=0.044), but still had a considerable rate of PD (CR: 26%, PR: 57%, SD: 100%). Those who progressed had numerically less cycles of ICI prior to treatment cessation (17 vs 32, p>0.05). Baseline disease factors, time to best response and duration of treatment after best response were not associated with PD. ICI was restarted in 8 of 14 pts (57%) with PD, with response rate to retreatment of 75% (4 CR, 2 PR, 1 SD, 1 PD – pt with leptomeningeal disease). Median time to best response at retreatment was 3 months (range 2 to 7), with all responses ongoing after a median of 10 months back on treatment. 3 pts had an isolated site of PD successfully treated with radiation therapy and remain in remission off ICI. Conclusions: ICI responses in mMCC do not appear as durable off treatment as in other cancers, including in patients who achieve a CR. Ongoing treatment should be considered, though initial data on response to retreatment is promising.[Table: see text]

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Complete Radiologic Response of Metastatic Pancreatic Ductal Adenocarcinoma to Microwave Ablation Combined with Second-Line Palliative Chemotherapy

Case Reports in Gastrointestinal Medicine ◽

10.1155/2020/4138215 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Hakon Blomstrand ◽

Karin Adolfsson ◽

Per Sandström ◽

Bergthor Björnsson

Keyword(s):

Adjuvant Chemotherapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Palliative Chemotherapy ◽

Lung Metastases ◽

Performance Status ◽

Progression Free Survival ◽

Disease Recurrence ◽

Ductal Adenocarcinoma ◽

Second Line ◽

First Line

Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, especially for the majority of patients diagnosed with metastatic disease. The primary option for palliative treatment is chemotherapy, and responses beyond first-line treatment are rare and typically short. Here, we report a case of a 63-year-old woman with PDAC in the head of the pancreas who was initially successfully treated by pancreaticoduodenectomy followed by adjuvant chemotherapy with gemcitabine. However, disease recurrence with liver and para-aortic lymph node metastases was detected only two months after the completion of adjuvant chemotherapy. First-line palliative chemotherapy with gemcitabine-nab/paclitaxel was commenced. The results were discouraging, with disease progression (liver and lung metastases) detected at the first evaluation; the progression-free survival was just two months (64 days). Surprisingly, the response to second-line palliative chemotherapy with 5-fluorouracil-oxaliplatin was excellent; in combination with the ablation of a liver metastasis, this treatment regimen resulted in a complete radiological response and an 11-month treatment-free interval with a sustained good performance status.

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A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5576 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5576-5576

Author(s):

S. Welch ◽

H. J. Mackay ◽

H. Hirte ◽

G. F. Fleming ◽

R. Morgan ◽

...

Keyword(s):

Phase Ii ◽

Kinase Inhibitor ◽

Phase Ii Study ◽

Objective Response ◽

Progression Free Survival ◽

Open Label ◽

Second Stage ◽

Best Response ◽

Grade 3 ◽

Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

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Safety, efficacy, and time to clinical response with bevacizumab plus FOLFIRI regimen in metastatic colorectal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15138 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15138-e15138

Author(s):

S. Tomao ◽

G. Spinelli ◽

L. Rossi ◽

G. Pasciuti ◽

G. Arcangeli ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Clinical Response ◽

Median Time ◽

Progression Free Survival ◽

Phase Iii ◽

Clinical Activity ◽

Efficacy And Safety ◽

First Line ◽

Ecog Ps

e15138 Background: Bevacizumab (BEV) has shown clinical activity in metastatic colorectal cancer patients (mCRC)and randomised phase III trials have demonstrated that this agent significantly improves overall and/or progression-free survival when added to first-line irinotecan based chemotherapy (CT) regimens. We evaluated the efficacy and safety of BEV plus FOLFIRI (irinotecan, 5- fluorouracil, and leucovorin) as first line treatment in 27 consecutive metastatic colorectal cancer cases, with the primary end point to calculate the median time to clinical response with this chemotherapeutic schedule. Methods: Between October 2007 and January 2008 we collected the data on 27 patients with mCRC treated with first line chemotherapy with BEV plus FOLFIRI. Elegibility criteria had to be: mCRC; no prior CT for metastatic disease; ECOG PS 0/1, adequate organ function; no CNS metastases. The treatment consisted of a minimum of six cycles of irinotecan plus infusional 5-FU/LV according to the classical FOLFIRI schedule; BEV (5mg/kg) was given on day 1 with CT and then every 2 weeks until disease progression. Safety and response were assessed at the time of first CT and every 4 weeks thereafter. Results: 27 pts were evaluable (male 18; median age 61 years (range 45–77), ECOG PS 0: 52%, PS 1: 48%. The sites of metastases were: liver (15 pts), lung (5 pts), liver and lung (5 pts), peritoneal wall (2 pts).Median follow-up was 18 weeks. Two patients had complete response(CR) and 13 pts partial response (PR), with an overall response rate of 57.7%. Five patients had stable disease and 6 patients showed progressive disease. A clinical benefit was demonstrated in 77 % of pts. We observed a median time to clinical response of 11 weeks, evaluated with tumor markers and with CT/NMR/US examinations. A grade 3 or 4 neutropenia was detected in 39% of pts and grade 2 or 3 hypertension in 9%. We did’nt observe cases of thrombosis, bleeding and gastrointestinal perforation, sometimes related to the use of BEV. Conclusions: In this little experience the efficacy and safety of BEV associated with FOLFIRI schedule, a first line therapy in mCRC,is consistent with results from other previous studies, showing moreover a short time to clinical response with this association. No significant financial relationships to disclose.

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The association of objective response and overall survival in patients with inoperable or metastatic gastric and esophagogastric junction (EGJ) cancer: A pooled analysis of individual patient data from first-line clinical trials.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4095 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4095-4095

Author(s):

Toki Anna Bolt ◽

Claudia Pauligk ◽

Dominique Werner ◽

Frank Mayer ◽

Ralf Dieter Hofheinz ◽

...

Keyword(s):

Overall Survival ◽

Survival Data ◽

Lung Metastases ◽

Objective Response ◽

Surrogate Marker ◽

Pooled Analysis ◽

Survival Times ◽

First Line ◽

Regional Lymph Nodes ◽

Ecog Ps

4095 Background: The aim of the study is to determine whether the achievement of an objective response to first-line chemotherapy is prognostic of patient’s outcome in gastric/EGJ adenocarcinoma. Methods: Individual patient (pts) data from prospective first-line trials conducted by a single study group were used. Patients received platin/5-FU based chemotherapy with or without docetaxel. Responses were evaluated according to WHO criteria in all trials. Response data, patients’ characteristics (age, sex, entity, histological type, primary location, ECOG PS, and type and number of metastatic sites), type of chemotherapy, and overall survival data were analyzed. Results: 612 pts were included. Median age was 66 yrs; 31.5% had ECOG status 0, 58.3% ECOG 1, and 9.8% ECOG 2 & 3. Gastric primaries were found in 44.4% and EGJ in 35.8% of pts (19.7% were overlapping/not evaluable). According to Lauren classification, 36.8% had intestinal, 32.4% diffuse, and 8.5% mixed types (22.4% were not classifiable). 64.5% had positive non-regional lymph nodes (LN) involvement, 14.1% LN involvement without other metastases, 33.3% had peritoneal carcinomatosis, 44.0% liver and 16.7% lung metastases. Response rates were complete (CR) in 3.1%, partial (PR) in 36.4%, stable disease (SD) in 34.5%, and progressive disease (PD) in 15.0% pts (10.9% were not evaluable). Overall response rate (OR; CR + PR) was 39.5%. Median overall survival times in pts with CR vs PR vs SD vs PD were 37.9 vs 14.7 vs 10.9 vs 5.2 months, respectively; p=1.26 x 10-33). OR (CR or PR) also strongly predicted OS (16.7 vs 8.1 months in pts with vs no OR, p=1.08 x 10-17). OR remained the strongest predictor of OS in the multivariate analysis (p=6.55 x 10-7) including all baseline criteria mentioned above followed by ECOG PS (p=0.048) and the presence of non-regional LN as the only site of metastasis (p=0.034). Conclusions: The achievement of an objective response is the strongest predictor of survival in pts with gastric and EGJ cancer and could serve as a surrogate marker if validated.

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Tumor shrinkage during VEGF inhibitor therapy as an independent predictor of PFS and OS in renal cell carcinoma (RCC).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.423 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 423-423

Author(s):

Viktor Gruenwald ◽

Jonas Busch ◽

Steffen Weikert ◽

Christoph Seidel

Keyword(s):

Tumour Size ◽

Progression Free Survival ◽

Predictive Marker ◽

Tumor Shrinkage ◽

First Line ◽

Vegf Inhibitors ◽

Vegf Inhibitor ◽

Kaplan Meier ◽

Best Response ◽

C 30

423 Background: Response to VEGF targeted therapies has been recently shown to be an important prognostic and predictive marker in metastatic RCC. However, whether the extent of tumor shrinkage (TS) correlates with distinct clinical outcome remains unknown. We investigated the role of early TS fractions on median progression free survival (PFS) and median overall survival (OS). Methods: Tumor evaluations according to RECIST 1.1 were performed within 3 months (mo) of targeted therapy with a VEGF inhibitor in 108 patients (pts). Pts were then categorized in fractions of TS: a) -100% to -60%; b) -60 % to -30% and c) -30% to 0% or gain in tumour size: d) 0% to +20% and e) > +20%. Kaplan-Meier and log-rank analyses were performed to estimate PFS and OS with a landmark set to 6 mo. Multivariate Cox proportional hazard model was utilized for evaluation of prognostic factors. Results: First-line VEGF inhibition achieved a PFS of 10.6 mo (95% CI 8.7 – 12.5) and an OS of 29.8 mo (95% CI 23.9 – 35.6) in all pts. 5 pts achieved a complete remission (4.6%), 28 pts a partial remission (25.9%), 52 pts. stable disease (48.2%), and 23 pts. had progressive disease (21.3%) as best response. In univariate analyses histology (clear cell differentiation vs. others) and TS were associated with PFS (p = 0.026; p <0.0001) and OS (p = 0.017; p = 0.009). Multivariate analyses confirmed the relevance of TS as a prognostic variable for OS (p = 0.021; HR 1.49) and PFS (p = <0.001; HR 1.91). Conclusions: TS is an independent predictive and prognostic marker in first-line treatment with VEGF inhibitors in mRCC. [Table: see text]

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Influence of tumor size and Eastern Cooperative Oncology Group performance status (ECOG PS) at baseline on patient (pt) outcomes in lenvatinib-treated radioiodine-refractory differentiated thyroid cancer (RR-DTC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6081 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6081-6081 ◽

Cited By ~ 3

Author(s):

Lori J. Wirth ◽

Sophie Leboulleux ◽

Naomi Kiyota ◽

Makoto Tahara ◽

Kei Muro ◽

...

Keyword(s):

Tumor Size ◽

Group Performance ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Disease Characteristics ◽

Kaplan Meier ◽

Ecog Ps ◽

Post Hoc

6081 Background: In SELECT, lenvatinib significantly improved progression-free survival (PFS) of pts with RR-DTC versus placebo (18.3 v 3.6 months; hazard ratio [HR]: 0.21 [99% CI: 0.14, 0.31]; P<0.001). Here we examine the treatment of RR-DTC with lenvatinib in relation to tumor size (sum of all targeted lesions) and ECOG PS. Methods: In this post hoc analysis of SELECT with pts randomized to receive lenvatinib, Kaplan-Meier estimates of time to ECOG PS ≥2 were calculated for subgroups of pts according to baseline ECOG PS or tumor size. Objective response rate (ORR) and Kaplan-Meier estimates of overall survival (OS) and PFS according to ECOG PS (0 or 1) at baseline were calculated. Correlations between ECOG PS at baseline (0 or 1) and maximum tumor shrinkage were calculated using one-way analysis of variance. Results: Pts with ECOG PS 0 or 1 at baseline had similar demographic and disease characteristics. ORR was 78.5% and 51.0% for pts with ECOG PS 0 and 1 at baseline, respectively (odds ratio [95% CI]: 3.508 [2.018, 6.097]). Mean maximum percent decrease in tumor size was significantly greater in pts with baseline ECOG PS 0 (-46.13%) versus pts with ECOG PS 1 (-37.16%; P=0.0017). For pts with ECOG PS 1 at baseline, time to ECOG PS ≥2 was numerically shorter with tumor size >60 mm versus tumor size ≤60 mm (HR [95% CI]: 1.450 [0.708, 2.967]). Additional results are summarized in the table. Conclusions: Among pts with RR-DTC, PFS, OS, ORR, and time to ECOG ≥2 were generally better for patients with lower ECOG PS or smaller tumor size at baseline. These results may indicate that it is beneficial to start lenvatinib in pts with RR-DTC early, before ECOG PS worsens and tumor size increases. Clinical trial information: NCT01321554. [Table: see text]

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