Cisplatin plus paclitaxel chemotherapy with or without bevacizumab in postmenopausal women with previously untreated advanced cervical cancer: a retrospective study

Abstract Background The aim of this study was to assess the survival outcomes of cisplatin-paclitaxel chemotherapy plus bevacizumab (CPB) versus cisplatin-paclitaxel chemotherapy alone (CPA) in postmenopausal women with previously untreated advanced cervical cancer (CC). Methods Consecutive postmenopausal women who experienced CPB or CPA were identified retrospectively from our medical centre during 2015–2019. Follow-up visits occurred 1 and 3 months after starting CPB or CPA. Afterwards, this assessment was conducted every 3 months for 1 year and then yearly thereafter. The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints were the frequency and severity of adverse events (AEs). Results Two hundred forty-six postmenopausal women were included (CPB, n = 124; CPA, n = 122). The median follow-up for the entire cohort was 24 months (range, 2–32). At the final follow-up, a significant difference was detected in terms of median OS (16.4 months [95% CI, 15.3–17.1] for CPB vs. 12.3 months [95% CI, 10.2–13.5] for CPA; hazard ratio (HR) 0.69, 95% CI, 0.49–0.99; p = 0.001), and the median PFS was longer in the CPB group than in the CPA group (9.2 months [95% CI, 8.3–10.7] vs. 7.9 months (95% CI, 6.1–8.6) (HR 0.62, 95% CI, 0.47–0.82; p < 0.001). There were significant differences in the number of AEs between the groups (hypertension grade ≥ 2 [p < 0.001], neutropenia grade ≥ 4 [p < 0.001], and thrombosis/embolism grade ≥ 3 [p = 0.030]). Conclusions Among postmenopausal women with previously untreated advanced CC, those who received CPB experienced superior survival benefits compared to those who received CPA. The safety profile for CPB was controllable despite the long duration of CPB use.

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Cetuximab versus bevacizumab following prior FOLFOXIRI and bevacizumab in postmenopausal women with advanced KRAS and BRAF wild-type colorectal cancer: a retrospective study

BMC Cancer ◽

10.1186/s12885-020-07770-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chunlong Huang ◽

Xiaoyuan Gu ◽

Xianshang Zeng ◽

Baomin Chen ◽

Weiguang Yu ◽

...

Keyword(s):

Postmenopausal Women ◽

Survival Benefit ◽

Progression Free Survival ◽

Wild Type ◽

Free Survival ◽

Primary Endpoints ◽

Significant Difference ◽

Inductive Treatment ◽

Advanced Colorectal Carcinoma

Abstract Background An upgraded understanding of factors (sex/estrogen) associated with survival benefit in advanced colorectal carcinoma (CRC) could improve personalised management and provide innovative insights into anti-tumour mechanisms. The aim of this study was to assess the efficacy and safety of cetuximab (CET) versus bevacizumab (BEV) following prior 12 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus BEV in postmenopausal women with advanced KRAS and BRAF wild-type (wt) CRC. Methods Prospectively maintained databases were reviewed from 2013 to 2017 to assess postmenopausal women with advanced KRAS and BRAF wt CRC who received up to 12 cycles of FOLFOXIRI plus BEV inductive treatment, followed by CET or BEV maintenance treatment. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rate. The secondary endpoint was the rate of adverse events (AEs). Results At a median follow-up of 27.0 months (IQR 25.1–29.2), significant difference was detected in median OS (17.7 months [95% confidence interval [CI], 16.2–18.6] for CET vs. 11.7 months [95% CI, 10.4–12.8] for BEV; hazard ratio [HR], 0.63; 95% CI, 0.44–0.89; p=0.007); Median PFS was 10.7 months (95% CI, 9.8–11.3) for CET vs. 8.4 months (95% CI, 7.2–9.6) for BEV (HR, 0.67; 95% CI 0.47–0.94; p=0.02). Dose reduction due to intolerable AEs occurred in 29 cases (24 [24.0%] for CET vs. 5 [4.8%] for BEV; p< 0.001). Conclusions CET tends to be superior survival benefit when compared with BEV, with tolerated AEs.

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Nontransplant Treatment Outcomes with Generic Novel Agents in Newly Diagnosed Multiple Myeloma Patients

Blood ◽

10.1182/blood.v126.23.5382.5382 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5382-5382

Author(s):

Chandran K Nair ◽

Vineetha Raghavan ◽

Atanu Bhattacharjee ◽

Satheesh Babu ◽

Sangeetha Nayanar

Keyword(s):

Treatment Outcomes ◽

Stem Cell Transplant ◽

Progression Free Survival ◽

Novel Agents ◽

Cell Transplant ◽

Free Survival ◽

Entire Cohort ◽

Grade 3 ◽

Stage 1

Abstract Introduction Introduction of novel agents (Immunomodulators-thalidomide/lenalidomide and proteasome inhibitors-bortezomib) has really changed the treatment outcomes in myeloma patients. This is applicable to patients both eligible and ineligible for autologous stem cell transplant. In developing countries, like India, access to the generic forms makes it easy for patients to have treatment with all types of novel agents. In this study, we did a retrospective audit of the treatment outcomes with the generic forms of novel agents in a group of transplant ineligible patients. Methodology All newly diagnosed myeloma cases from January 2011 to December 2014, who did not undergo stem cell transplant, were included for the study. Criteria for diagnosis and treatment response were according to the latest IMWG guidelines. Baseline demographic data and details regarding CRAB criteria, Performance Status (PS), comorbidities, type and duration of treatment, and toxicity were recorded. Toxicity was graded according to CTCAE v 4. Only the maximum grade of a particular toxicity per patient has been reported. Dates of death if applicable was noted, and if patients were alive, date of last follow up was documented. Survival was analysed by non-parametric methods (Kaplan Meier and Cox proportional hazard model) and the variables considered were 'treatment completed' versus 'not completed', 'response' (PR or more) versus 'no response', 'maintenance received' versus 'not received', 'age ≤65 years' versus 'age >65 years', and international staging system (ISS) ' stage 1' versus 'stage 2 or 3'. Analysis was performed with R v 3.2.0 (http://cran.r-project.org.) Results One hundred and nineteen patients (53 males, 66 females) with median age of 62 years (range 44-85) were included as per eligibility criteria. Eighty four (70%) patients had IgG, and 21 (17.6%) had IgA, and 14 (11.7%) had light chain myeloma. Twenty two (18.4%) patients were in ISS stage 1, 36 (30%) were in stage 2 and 39 (32.7%) were in stage 3, with data missing in 22 patients. Fifty seven (47.9%) patients were having comorbidity. Ninety seven patients (81%) were having PS ≤ 2 and 21(17.6%) had PS >2. Lenalidomide based regimen was given in 29 patients, thalidomide based in 65 and bortezomib based in 25 patients. Overall response (PR or more) was documented in 74 (72%), out of 102 evaluable patients. VGPR or more was documented in 56 (55%), and PR in 18(17.6%) patients. Seventy three (61%) patients had some form of toxicity. Grade 3 nonhematologic toxicity occurred in 7 patients (peripheral neuropathy in 2, diarrhea in 2 and DVT in 3), grade 4 in none. Grade 3-4 hematologic toxicity occurred in 8 patients (grade 3 anemia and thrombocytopenia in 3 each, and grade 4 thrombocytopenia in 2 patients). Median follow up duration was 22 months. Estimated 3 year OS for entire group was 60% (95 % CI 47-77%) (Figure 1). Median PFS was 22 months (95 % CI 19- 25) (Figure 2). Variables significantly predicting OS were, treatment completed or not (47 Vs 32 months, HR= 0.372, P= 0.011) and age ≤ 65 versus age >65(47 Vs 31 months, HR= 4.15, P<0.001). Similarly for PFS the significant variables were response or not (24 Vs 7 months, HR= 4.89, P<0.001) and ISS stage 1 Vs stage 2 or 3 (25 Vs 19 months, HR=2.39, P=0.021). Conclusion Treatment with the generic forms of novel agents leads to comparable response rates and survival in patients with myeloma. So, use of these agents with lower cost seems justifiable in the real world practice where it may be difficult to access the innovators for the exuberant cost. Figure 1. Overall survival for the entire cohort Figure 1. Overall survival for the entire cohort Figure 2. Progression free survival for the entire cohort Figure 2. Progression free survival for the entire cohort Disclosures No relevant conflicts of interest to declare.

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Paclitaxel, ifosfamide, and cisplatin regimen as neoadjuvant chemotherapy in young women with locally advanced squamous cervical cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5587 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5587-5587

Author(s):

M. Marinaccio ◽

E. De Marino ◽

E. Mele ◽

R. Catacchio ◽

C. Pellegrino ◽

...

Keyword(s):

Cervical Cancer ◽

Neoadjuvant Chemotherapy ◽

Young Women ◽

Radical Surgery ◽

Locally Advanced ◽

Young Patients ◽

Progression Free Survival ◽

Advanced Cervical Cancer ◽

Curative Radiotherapy

5587 Background: Chemoradiotherapy is the standard treatment of advanced cervical cancer. Neoadjuvant chemotherapy (NAC) may represent an alternative for locally advanced cervical cancer (LACC).This study was undertaken to evaluate the efficacy of NAC in young patients with squamous LACC. Methods: Since 2000 to 2008, 61 pts (mean age 43 yrs) with squamous LACC were treated with NAC and afterwards evaluated for radical surgery. Eligibility included proven histologically diagnosis of squamous cervical carcinoma, FIGO stage IB2/IIA>4cm/IIB, measurable disease, ECOG PS 0–2, no prior therapy and age under 49 years. All patients received TIP regimen (cisplatin 50 mg/m2 i.v. day 1, paclitaxel 175 mg/m2 over 3 hrs i.v.day1, ifosfamide 5,000 mg/m2 plus mesna 6,000 mg/m2 over 24 hrs i.v. day 1–2). Each cycle was repeated every 21 days. Patients were evaluated 4–6 weeks after the completion of the third cycle with the purpose to perform radical surgery according to clinical response. Results: 35pts (57.4%) were stage IB2; 9 (14.7%) were IIA >4cm; and 17 (27.9%) were IIB. After restaging the clinical results were: CR = 4/61 (6.6%), PR = 51/61 (83.6%); no response = 5/61 (8.2%); progression = 1/61 (1.6%). A total of 55 pts (90.1%) were eligible for surgery; 6/61 pts (9.8%) were submitted to curative radiotherapy (until 2004) or chemoradiotherapy. Pathological responses after surgery were: 4 pCR (7.3%); 46 pPR (83.6%); and 5 (9.1%) pPR with presence of positive surgical margins or metastatic lymph nodes. Out of 55 pts, 50 received 2 cycles of TIP regimen as a consolidation therapy before follow-up; 5 pts with incomplete pPR underwent radio/chemoradiotherapy. After NAC an overall downstaging of LACC was obtained in 50/61 pts (82.0%). In this group of pts at the median follow-up of 42 months (range 4–98) updated as of December 2008, the 3-years progression-free survival and overall survival are 85.9% and 82.0%, respectively. Conclusions: Our results indicate that TIP regimen-based NAC is an attractive option in young women with squamous LACC (IB2,IIA >4cm, IIB) that strongly desire surgery.The rate of patients with a prolonged remission of disease (82.0%) suggests that the clinical benefit of TIP regimen-based NAC followed by surgery may be comparable to chemoradiotherapy. No significant financial relationships to disclose.

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Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1038 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1038-1038 ◽

Cited By ~ 28

Author(s):

Gabriel N. Hortobagyi ◽

Salomon M. Stemmer ◽

Howard A. Burris ◽

Yoon Sim Yap ◽

Gabe S. Sonke ◽

...

Keyword(s):

Postmenopausal Women ◽

Safety Data ◽

Progression Free Survival ◽

P Value ◽

First Line ◽

Treatment Benefit ◽

Prior Therapy ◽

Hormone Receptor Positive ◽

Grade 3

1038 Background: Endocrine therapy (ET) is the basis of first-line (1L) treatment for HR+ ABC. However, ET resistance are almost universal. At the first interim analysis (IA) of MONALEESA-2 (NCT01958021), ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor) + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + LET in patients (pts) with HR+, HER2– ABC.1 Here we report updated efficacy and safety data from MONALEESA-2 with a further ~11 months of follow-up. Methods: Postmenopausal women with no prior therapy for ABC were randomized 1:1 toRIB (600 mg/day, 3-weeks-on/1-week-off) + LET(2.5 mg/day, continuous) vs PBO + LET. The primary endpoint was locally assessed PFS. Secondary endpoints include overall survival (OS; key) and safety. OS significance was defined by a p-value threshold of 3.15 x 10-5. Tumor assessments were performed every 8 weeks for the first 18 months, and every 12 weeks, thereafter. Results: 668 pts were enrolled (334 in each arm). At the second IA for OS (data cut-off Jan 2, 2017), the median duration of follow-up was 26.4 months; 116 deaths and 345 PFS events had occurred. OS data remain immature, with 15.0% vs 19.8% of pt deaths in the RIB + LET vs PBO + LET arm (HR = 0.746; 95% CI: 0.517–1.078; p= 0.059). Updated PFS analyses confirmed continued treatment benefit in the RIB + LET vs PBO + LET arm. The 24-month PFS rates (RIB + LET vs PBO + LET) were 54.7% vs 35.9%. Treatment benefit was consistent across pt subgroups. The most common Grade 3/4 laboratory abnormalities (≥10% of pts; RIB + LET vs PBO + LET) were decreased neutrophils (62.6% vs 1.5%), decreased leukocytes (36.8% vs 1.5%), decreased lymphocytes (16.2% vs 3.9%), and elevated alanine aminotransferase (11.4% vs 1.2%). Conclusion: After 26+ months of follow-up, treatment benefit with 1LRIB + LET persists in postmenopausal women with HR+, HER2– ABC. The study remains immature for OS analysis. The safety profile of RIB + LET remains manageable. 1. Hortobagyi G, et al. N Engl J Med 2016;375:1738–48. Clinical trial information: NCT01958021.

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Long-Term Toxicity and Efficacy of Intensity-Modulated Radiation Therapy in Cervical Cancers: Experience of a Cancer Hospital in Pakistan

JCO Global Oncology ◽

10.1200/go.20.00169 ◽

2020 ◽

pp. 1639-1646

Author(s):

Muhammad Atif Mansha ◽

Tabinda Sadaf ◽

Asmara Waheed ◽

Amna Munawar ◽

Asma Rashid ◽

...

Keyword(s):

Cervical Cancer ◽

Radiation Therapy ◽

Lymph Node ◽

Tumor Size ◽

Intensity Modulated Radiation Therapy ◽

Disease Free Survival ◽

Intensity Modulated ◽

Significant Difference ◽

Grade 3

PURPOSE To report the chronic toxicity and disease outcomes attributable to intensity-modulated radiation therapy (IMRT) in patients with cervical cancer. METHODS AND MATERIALS Between January 2014 and December 2018, a retrospective review of medical records of patients with cervical cancer who received radiation therapy with IMRT was performed. Disease and treatment-related details were documented. Follow-up notes were reviewed, and severity of late toxicities was recorded. Overall survival (OS) and disease-free survival (DFS) at 3 years were estimated. RESULTS A total of 222 patients’ records were reviewed. Mean age was 50.7 years. Median follow-up duration was 33 months (range, 2-70 months). The most common toxicity was vaginal stricture (grade 2, n = 59, 26.6%; grade 3, n = 4, 1.80%), followed by proctitis (grade 2, n = 24; 10.8%; grade 3, n = 7; 3.20%). Seven patients (grade 2, n = 5, 2.3%; grade 3, n = 2; 0.90%) developed cystitis, and only 5 (grade 2; 2.3%) were found to have colitis. None of the patients had grade 4 or grade 5 toxicities. There was a significant difference in late complications in patients with nodal disease or those who underwent prior surgery ( P < .05). Three-year OS and DFS rates were 79.7% and 81.9%, respectively. Patients with tumor size > 5 cm and those with pelvic lymph node metastasis had poor survival rates ( P < .05). CONCLUSION IMRT is an effective and well-tolerated technique that should be considered in patients with lymph node disease and in postoperative patients. There is an inverse relationship between tumor size and nodal involvement with respect to OS and DFS.

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Safety of everolimus for women over age 65 with advanced breast cancer (BC): 12.5-month follow-up of BOLERO-2.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.27_suppl.104 ◽

2012 ◽

Vol 30 (27_suppl) ◽

pp. 104-104 ◽

Cited By ~ 3

Author(s):

Hope S. Rugo ◽

Howard A. Burris ◽

Michael Gnant ◽

José Baselga ◽

Martine J. Piccart-Gebhart ◽

...

Keyword(s):

Elderly Patients ◽

Postmenopausal Women ◽

Mammalian Target Of Rapamycin ◽

Safety Data ◽

Progression Free Survival ◽

Phase Iii ◽

Tolerability Profile ◽

Once Daily ◽

Grade 3

104 Background: Postmenopausal women with estrogen-receptor–positive (ER+) BC who relapse/progress on a nonsteroidal aromatase inhibitor (NSAI) are usually treated with the steroidal AI exemestane (EXE), but there is no currently approved treatment for this indication. The BOLERO-2 trial showed that adding everolimus (EVE), an oral inhibitor of mammalian target of rapamycin (mTOR), to EXE significantly improved clinical benefit beyond that of EXE alone (Hortobagyi et al, SABCS 2011, Abstract S3-7). As many women with advanced BC are elderly, the tolerability profile of EVE + EXE in this population is of interest. Methods: BOLERO-2 is a phase III, randomized trial comparing EVE (10 mg once daily) vs placebo (PBO), both plus EXE (25 mg once daily), in postmenopausal women with advanced ER+ BC progressing or recurring after NSAIs. Safety data with a focus on elderly patients are reported at 12.5 months’ median follow-up. Results: Baseline disease characteristics, age, and prior cancer therapy were well balanced between treatment arms (N = 724). At 12.5 months’ median follow-up, the addition of EVE to EXE significantly improved progression-free survival in patients <65 (HR, 0.37; p < .05) or ≥65 years of age (HR, 0.56; p < .05). Adverse events (AEs) of special interest (all grades) occurring more frequently with EVE vs PBO (overall study population) included stomatitis (66.6% vs 11.3%), infection (50.4% vs 25.2%), rash (44.0% vs 8.4%), pneumonitis (18.7% vs 0.4%), and hyperglycemia (15.4% vs 2.5%). Elderly EVE-treated patients (≥65 years) had similar or marginally lower incidence of stomatitis (52.1%), rash (32.3%), pneumonitis (14.6%), and hyperglycemia (12.5%) compared with the overall population. Grade 3-4 AEs in patients ≥70 years of age (n = 161) reported only among patients receiving EVE (n = 118) included fatigue (10.2%), anemia (10.2%), hyperglycemia (8.5%), stomatitis (7.6%), dyspnea (6.8%), pneumonitis (5.1%), neutropenia (3.4%), and hypertension (3.4%). Conclusions: Adding EVE to EXE was well tolerated in the overall population and in elderly patients with advanced BC; grade 3-4 AEs were uncommon and manageable. Overall, AEs were consistent with the known safety profile of EVE.

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Treatment-free survival after discontinuation of immuno-checkpoint therapy, and outcome of subsequent molecular targeted therapy: Retrospective study of Japanese metastatic renal cell carcinoma patients (after I-O study).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.677 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 677-677

Author(s):

Yoshihiko Tomita ◽

Go Kimura ◽

Satoshi Fukasawa ◽

Yutaka Sugiyama ◽

Kazuyuki Numakura ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Progression Free Survival ◽

Free Survival ◽

Primary Endpoints ◽

Secondary Endpoints ◽

Grade 3

677 Background: Guidelines for treatment of metastatic renal cell carcinoma (mRCC) recommend nivolumab monotherapy (NIVO) for treated mRCC, and nivolumab + ipilimumab combination therapy (NIVO+IPI) for untreated IMDC intermediate and poor risk mRCC patients. Though molecular targeted therapies (TTs) such as VEGFR-TKIs and mTORi are recommended as subsequent therapy after NIVO or NIVO+IPI, their impact is still unclear. Methods: Japanese mRCC patients treated with TT after NIVO (CheckMate 025) or NIVO+IPI (CheckMate 214) were retrospectively analyzed. Primary endpoints were investigator assessed ORR of the first TT after NIVO, and after NIVO+IPI. Secondary endpoints included treatment-free survival (TFS) after discontinuation of NIVO and NIVO+IPI, and progression-free survival (PFS) and safety of the first subsequent TT after NIVO and NIVO+IPI. Results: Twenty-six patients of CheckMate 025 and 19 patients of CheckMate 214 from 20 centers in Japan were analyzed. Median TFS after ICI discontinuation was 1.0m and 2.5m for CheckMate 025 and CheckMate 214 patients, respectively. Median follow-up period from the start of TT after ICI discontinuation to date of analysis or death was 22.1m for CheckMate 025, and 20.3m for CheckMate 214 patients. As the first subsequent TT after NIVO or NIVO+IPI, axitinib was the most treated therapy for both CheckMate 025 (53.8%) and CheckMate 214 (47.4%) patients. ORR of TT after NIVO and NIVO+IPI was 26.9% and 31.6%, and median PFS was 8.9m and 16.3m, respectively. During the treatment of first TT after NIVO and NIVO+IPI, 98% percent experienced treated-related adverse events, 51% experienced grade 3-4, but no treatment related death. Conclusions: TTs have favorable antitumor activity for mRCC after NIVO and NIVO+IPI, possibly by changing the mode of action. Safety signals of TTs after ICI were similar to the previous reports. These results indicate sequential TTs after ICI may contribute for durable survival benefit.

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Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial

Journal of Clinical Oncology ◽

10.1200/jco.20.01920 ◽

2020 ◽

Vol 38 (34) ◽

pp. 4095-4106

Author(s):

Chunyan Lan ◽

Jingxian Shen ◽

Yin Wang ◽

Jundong Li ◽

Zhimin Liu ◽

...

Keyword(s):

Cervical Cancer ◽

Phase Ii ◽

Kinase Inhibitor ◽

Objective Response ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Advanced Cervical Cancer ◽

Open Label ◽

Duration Of Response ◽

Grade 3

PURPOSE Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

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357 Toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.357 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A384-A384

Author(s):

Xiaoting Xu ◽

Jian Huan ◽

Hui Miao ◽

Hao Wang ◽

Yue Wang ◽

...

Keyword(s):

Cervical Cancer ◽

Treatment Options ◽

Objective Response ◽

Stage Iv ◽

Progression Free Survival ◽

Complete Response ◽

Open Label ◽

Nccn Guidelines ◽

Significant Difference ◽

Grade 3

BackgroundRecurrent or metastatic cervical cancer patients who progressed after standard therapy have limited treatment options and poor prognosis with a 1-year survival rate ranging between 15% and 20%. This study evaluates the efficacy and safety of toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer (Clinical trial ID: ChiCTR2000029068)MethodsIn this open-label, single-arm, phase 2 study conducted at four radiotherapy centers in East China, eligible patients were confirmed by pathology and/or imaging for recurrent or metastatic cervical cancer. According to the first-line therapies for cervical cancer recommended by NCCN guidelines, all patients were received paclitaxel plus cisplatin regimen, with or without bevacizumab, combined with radiotherapy. After seven fractions radiotherapy at the recurrent or metastatic regions, 240 mg toripalimab every three weeks for six cycles or more were given in combination.ResultsBetween Jan 14th, 2020, and May 1st, 2021, 24 patients were enrolled. All patients were staged at the first visit, as seven patients were with FIGO (2018) stage I, 10 with stage II, 2 with stage III, 1 with stage IV, and 2 with unclear stage. Of 24 included patients, 22 (91.67%) had squamous cervical cancer. The median age was 55 (range, 33–72) years. As of May 31, 2021, median follow-up time was 8.5 months [95% CI: 2.3–10.1]. 14 (58.3%) of 24 patients who achieved an objective response, including 10 (41.7%) complete response (CR) and 4 (16.7%) partial response (PR). The median duration of response was not reached and 7 (29.1%) patients continued toripalimab treatment after the previous 6-cycle immunotherapy. The disease control rate was 75% (18/24). Median progression-free survival (PFS) was 8.61 months (95% CI: 4.14–not reached). For subgroup analysis, the median PFS was significantly prolonged in the CR/PR group compared with that in the SD/PD group [not reached (95% CI: 6.21–not reached) versus 5.5 months (95% CI: 2.69–6.870), P = 0.023]. There was no significant difference in the median PFS between patients who previously received radiotherapy (8.61 months) and those who didn’t (6.87 months) (P = 0.641). 8 (33.3%) patients had grade 3–4 treatment-related adverse events (TRAEs). The most common grade 3-4 TRAEs were myelosuppression (29.2%), hypertriglyceridemia (8.3%), hypoalbuminemia (4.2%), pneumonia (4.2%), and hypercholesterolemia (4.2%).ConclusionsToripalimab plus chemoradiotherapy showed promising antitumor activity and tolerable toxicities in patients with recurrent or metastatic cervical cancer.

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CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9506 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9506-9506

Author(s):

Jedd D. Wolchok ◽

Vanna Chiarion-Sileni ◽

Rene Gonzalez ◽

Jean-Jacques Grob ◽

Piotr Rutkowski ◽

...

Keyword(s):

Systemic Therapy ◽

Objective Response ◽

Progression Free Survival ◽

Additional Treatment ◽

Advanced Melanoma ◽

Phase 3 ◽

Primary Endpoints ◽

Secondary Endpoints ◽

Grade 3

9506 Background: In the phase 3 CheckMate 067 trial, a durable and sustained clinical benefit was achieved with nivolumab (NIVO) + ipilimumab (IPI) and NIVO alone vs IPI at 5-y of follow-up (overall survival [OS] and progression-free survival [PFS] rates: 52%, 44%, 26% and 36%, 29%, 8%, respectively). Here we report 6.5-y efficacy and safety outcomes. Methods: Eligible pts with previously untreated unresectable stage III or IV melanoma were randomly assigned in a 1:1:1 ratio and stratified by PD-L1 status, BRAF mutation status, and metastasis stage. Pts received NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W followed by NIVO 3 mg/kg Q2W (n = 314), NIVO 3 mg/kg Q2W + placebo (n = 316), or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Co-primary endpoints were PFS and OS with NIVO + IPI or NIVO vs IPI. Secondary endpoints included objective response rate (ORR), descriptive efficacy assessments of NIVO + IPI vs NIVO alone, and safety. Results: With a minimum follow-up of 6.5 y, median OS was 72.1 mo with NIVO + IPI, 36.9 mo with NIVO, and 19.9 mo with IPI (table). Median time from randomization to subsequent systemic therapy was not reached (NR; 95% CI, 59.6–NR) with NIVO + IPI, 25.2 mo (95% CI, 16.0–43.2) with NIVO, and 8.0 mo (95% CI, 6.5–8.7) with IPI; 36%, 49%, and 66% of pts, respectively, received any subsequent systemic therapy. Median treatment-free interval (which excluded pts who discontinued follow-up prior to initiation of subsequent systemic therapy) was 27.6 mo (range, 0–83.0), 2.3 mo (range, 0.2–81.6), and 1.9 mo (range, 0.1–81.9) with NIVO + IPI, NIVO, and IPI, respectively. Of the pts alive and in follow-up, 112/138 (81%; NIVO + IPI), 84/114 (74%; NIVO), and 27/63 (43%; IPI) were off treatment and never received subsequent systemic therapy; 7, 8, and 0 pts, respectively, were still on treatment. Grade 3/4 treatment-related adverse events were reported in 59% of NIVO + IPI-treated pts, 24% of NIVO-treated pts, and 28% of IPI-treated pts. Since the 5-y analysis, no new safety signals were observed and no additional treatment-related deaths occurred. Conclusions: This 6.5-y analysis represents the longest follow-up from a phase 3 melanoma trial in the modern checkpoint inhibitor combination therapy and targeted therapy era. The results show durable improved outcomes with NIVO + IPI and NIVO vs IPI in pts with advanced melanoma. We observed improvement in OS, PFS, and ORR with NIVO + IPI over NIVO alone. Clinical trial information: NCT01844505. [Table: see text]

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