A selection of the latest clinical oncology literature (2.6-2.12)

In this issue of Featured Latest Clinical Oncology Literature, we provide our readers with a selection of articles published in reputable journals on breast cancer, cervical cancer, multiple myeloma, prostate cancer, and predictive immune checkpoint inhibitor therapy for metastatic melanoma The latest research results of clinical multivariate models of tumor
.

NEJM: The results of the KEYNOTE-522 study confirmed that in patients with early-stage triple-negative breast cancer, pembrolizumab plus neoadjuvant chemotherapy (adjuvant pembrolizumab after surgery) significantly prolonged the duration of the disease compared with neoadjuvant chemotherapy alone.
Event lifetime
.

The EMPOWER-Cervical 1/GOG-3016/ENGO T-cx9 trial demonstrated that cemiplimab significantly prolonged survival compared with single-agent chemotherapy in patients with recurrent cervical cancer following first-line platinum-based chemotherapy
.

Lancet Oncol: Long-term follow-up results of the ICARIA-MM study show that Ixatuximab combined with pomalidomide/dexamethasone regimen in patients with relapsed/refractory multiple myeloma can achieve sustained overall survival benefit and is safe Sex is controllable
.

JAMA Oncol: VIABLE trial suggests that autologous dendritic cell immunotherapy combined with docetaxel and prednisone in patients with metastatic castration-resistant prostate cancer is well tolerated and safe, but does not prolong overall survival period
.

J Clin Oncol: A cohort study establishes a multivariate model that effectively predicts efficacy and survival of immune checkpoint inhibitor therapy with or without ipilimumab in metastatic melanoma Response and survival outcomes in patients with metastatic melanoma treated with immunotherapy and can serve as a valuable tool for clinical decision-making
.

Clin Cancer Res: A phase 2 trial found that the combination of neratinib and fulvestrant showed antitumor activity in patients with estrogen receptor-positive, HER2-mutant metastatic breast cancer with a manageable safety profile
.

01 Pembrolizumab + neoadjuvant chemotherapy significantly prolongs event-free survival in triple-negative breast cancer The main treatment for triple-negative breast cancer is chemotherapy, but radical systemic chemotherapy based on anthracyclines and taxanes is used.
Patients with negative breast cancer still have shorter overall survival than patients with other subtypes of breast cancer
.

Neoadjuvant chemotherapy is the current standard of care for patients with early-stage triple-negative breast cancer
.

The short-term goal of neoadjuvant therapy is to achieve pathological complete remission, and the long-term goal is to prevent the recurrence and metastasis of triple-negative breast cancer
.

However, a higher risk of recurrence and death remains
.

On February 3, 2022, the "New England Journal of Medicine" (NEJM) published the event-free survival results of the KEYNOTE-522 trial [1], showing that in patients with early-stage triple-negative breast cancer, compared with neoadjuvant chemotherapy alone, parenchymal Bolizumab plus neoadjuvant chemotherapy (adjuvant pembrolizumab after surgery) significantly prolonged event-free survival
.

KEYNOTE-522 is a randomized, double-blind, placebo-controlled trial that enrolled patients with stage II-III treatment-naïve triple-negative breast cancer, randomized 2:1
.

Neoadjuvant chemotherapy was administered with paclitaxel and carboplatin followed by anthracycline, and the experimental group was administered intravenous pembrolizumab at the same time as neoadjuvant chemotherapy
.

Postoperative radiotherapy or not is determined by each research center according to the condition
.

Pembrolizumab was continued postoperatively
.

The two primary endpoints were pathological complete response at definitive surgery and event-free survival (see "Which prognostic marker is appropriate for early-stage triple-negative breast cancer? | Implications for KEYNOTE-522")
.

From March 2017 to September 2018, a total of 1,174 patients were randomly assigned to the experimental group (784 patients) or the control group (390 patients)
.

The median follow-up duration was 39.
1 months
.

An event or death occurred in 123 patients (15.
7%) in the experimental group and in 93 patients (23.
8%) in the control group (hazard ratio, 0.
63; 95% CI, 0.
48 to 0.
82; P<0.
001)
.

Event-free survival was significantly improved in the experimental group compared with the control group
.

At 36 months, the estimated event-free survival rates for the experimental and control groups were 84.
5% (95% CI, 81.
7 to 86.
9) and 76.
8% (95% CI, 72.
2 to 80.
7), respectively; Event lifetime
.

The event-free survival benefit in the trial arm was generally consistent across all prespecified subgroups, including those defined by PD-L1 expression status and nodal involvement
.

Analysis of distant progression-free and distant recurrence-free survival showed a hazard ratio of 0.
61 (95% CI, 0.
46 to 0.
82) for distant progression, distant recurrence, or death in the trial arm
.

Overall survival data were immature at the time of this interim analysis
.

Eighty patients (10.
2%) in the experimental group and 55 patients (14.
1%) in the control group died (hazard ratio, 0.
72; 95% CI, 0.
51 to 1.
02)
.

At 36 months, the estimated overall survival rates were 89.
7% (95% CI, 87.
3 to 91.
7) and 86.
9% (95% CI, 83.
0 to 89.
9) in the experimental and control groups, respectively; median overall survival was not reached in either group period
.

2 Treatment-related serious adverse events occurred in 34.
1% of patients in the experimental group and 20.
1% in the control group
.

Treatment-related adverse events resulted in the death of 4 patients (0.
5%) in the experimental group and 1 patient (0.
3%) in the control group
.

Immune-mediated adverse events occurred in 33.
5% of patients in the experimental group and 11.
3% in the control group; grade ≥3 immune-mediated adverse events occurred in 12.
9% and 1.
0% of patients in the two groups, respectively
.

The event-free survival results of KEYNOTE-522 with a median follow-up of 39 months suggest that regardless of PD-L1 expression status, pembrolizumab combined with neoadjuvant chemotherapy and continued use in the adjuvant phase can improve survival compared with placebo , which has opened up a new situation for the immunotherapy of high-risk early triple-negative breast cancer
.

02cemiplimab significantly prolongs survival in patients with recurrent cervical cancer There are approximately 600,000 new cases of cervical cancer and 350,000 cervical cancer deaths worldwide each year
.

Patients with relapsed disease who were unable to undergo radical pelvic excision, and those with metastases, received platinum-based chemotherapy with or without bevacizumab
.

Although antiangiogenic therapy improved overall survival, most patients progressed after first-line platinum therapy
.

Patients who have progressed after first-line platinum-based therapy have limited treatment options
.

Cemiplimab is a high-affinity fully human PD-1 monoclonal antibody active against recurrent cervical cancer
.

On February 3, 2022, NEJM published the results of the EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial [2], which confirmed that in patients with recurrent cervical cancer after first-line platinum chemotherapy, compared with single-agent chemotherapy, Cemiplimab significantly prolonged survival
.

This is a multicenter, open-label, phase 3 trial of patients with recurrent or metastatic cervical cancer whose disease has progressed after first-line platinum-based chemotherapy
.

Enrolled patients were randomly assigned in a 1:1 ratio to receive cemiplimab or chemotherapy of the investigator's choice
.

The primary endpoint was overall survival
.

The investigators also assessed progression-free survival and safety
.

From July 2017 to August 2020, a total of 608 patients (304 in each arm) were enrolled in the trial
.

After a median follow-up of 18.
2 months, median overall survival was longer in the cemiplimab group than in the chemotherapy group in the overall trial population (12.
0 months vs.
8.
5 months; hazard ratio for death, 0.
69; 95% CI, 0.
56-0.
84 ; two-sided P<0.
001)
.

The overall survival benefit was consistent across the two histological subgroups (squamous cell carcinoma and adenocarcinoma [including adenosquamous])
.

In the overall population, progression-free survival was also longer in the cemiplimab group than in the chemotherapy group (HR for disease progression or death, 0.
75; 95% CI, 0.
63-0.
89; two-sided P<0.
001)
.

In the overall population, the objective response rate was 16.
4% (95% CI, 12.
5-21.
1) in the cemiplimab group and 6.
3% (95% CI, 3.
8-9.
6) in the chemotherapy group
.

Among patients treated with cemiplimab, the objective response rate was 18% (95% CI, 11-28) and 11% in patients with PD-L1 expression levels ≥1% and PD-L1 expression levels <1%, respectively % (95% CI, 4-25)
.

Overall, 45.
0% of patients in the cemiplimab group and 53.
4% ​​of patients in the chemotherapy group had adverse events of grade 3 or higher
.

The most common grade 3 or higher adverse events were anemia (12.
0% in the cemiplimab group and 26.
9% in the chemotherapy group), urinary tract infection (5.
0% and 2.
8%), and neutropenia (1.
0% and 9.
0%)
.

Twenty-six patients (8.
7%) in the cemiplimab group and 15 patients (5.
2%) in the chemotherapy group discontinued treatment due to adverse events
.

Deaths occurred in 1.
7% and 0.
7% of patients in the two groups, respectively, but the investigators did not believe the deaths were related to cemiplimab
.

The trial demonstrated that in patients with recurrent cervical cancer whose disease had progressed after first-line platinum-based chemotherapy, survival was significantly longer with cemiplimab than with single-agent chemotherapy
.

Trial results suggest that some patients with recurrent cervical cancer may benefit from treatment with cemiplimab
.

03Ixatuximab combined with pomalidomide/dexamethasone regimen can achieve long-term survival in patients with relapsed/refractory multiple myeloma Multiple myeloma (MM) is a malignant disease of abnormal proliferation of plasma cells , is the second most common malignant tumor of the blood system in many countries, and it is still incurable
.

Treatment options for most patients include proteasome inhibitors, immunomodulators, steroids, alkylating agents, and monoclonal antibodies
.

Autologous stem cell transplantation is available in eligible patients
.

When the tumor recurs, the choice of next treatment is influenced by drug exposure and response to previous treatment regimens, and patients with relapsed and refractory MM are in urgent need of new treatments
.

Ixatuximab is an IgG1 chimeric monoclonal antibody that targets a specific epitope of the plasma cell CD38 receptor and can directly induce apoptosis and activate natural killer cells
.

CD38 is expressed at high levels on multiple myeloma cells and is a cell surface receptor target for antibody therapy in MM and other malignancies
.

On February 10, 2022, Lancet Oncol published online the updated long-term follow-up results of the ICARIA-MM study [3], showing that ixatuximab combined with pomalidomide/dexamethasone regimen in the treatment of relapsed/refractory MM Patients can obtain a sustained benefit in overall survival, and the safety is controllable
.

ICARIA-MM is a randomized, open-label, multicenter trial in which investigators screened 387 patients between January 10, 2017, and February 2, 2018, and eventually included 307 patients with relapsed/refractory MM , assigned to the ixatuximab group (Ixatuximab combined with pomalidomide and dexamethasone, n=154) or the control group (pomalidomide combined with low-dose dexamethasone, n=153), these patients had received at least two treatments including lenalidomide and proteasome inhibitors, and the last treatment failed
.

Prespecified overall survival outcomes were updated 24 months after the primary analysis to further assess the therapeutic status of ixatuximab in relapsed/refractory multiple myeloma
.

The median follow-up time was 35.
3 months, and the median overall survival was 24.
6 months (95% CI, 20.
3-31.
3) in the isatuximab group and 17.
7 months (14.
4-26.
2) in the control group (HR, 0.
76 ; 95% CI, 0.
57–1.
01; one-sided P=0.
028)
.

Investigator-assessed median progression-free survival was 11.
1 months (95% CI, 7.
8-13.
8) in the ixatuximab group and 5.
9 months (4.
5-7.
9) in the control group (HR, 0.
60; 95%) CI, 0.
46-0.
78; one-sided P<0.
0001)
.

In terms of safety, no new safety signals were found in the ixatuximab group as a whole
.

Serious treatment-related adverse events occurred in 73% and 60% of the ixatuximab group and control group, respectively
.

The most common adverse events of grade 3 or higher in the isatuximab and control groups were neutropenia (50% vs.
35%), pneumonia (23% vs.
21%), and thrombocytopenia (13 % vs.
12%)
.

Two treatment-related deaths (1%) occurred in the ixatuximab group (1 sepsis and 1 cerebellar infarction) and 2 treatment-related deaths (1%) in the control group
.

The addition of ixatuximab to the pomalidomide/dexamethasone regimen can significantly improve the progression-free survival of patients with relapsed and refractory MM and increase the objective response rate of patients
.

The results of this long-term follow-up confirmed that the combination of ixatuximab and pomalidomide/dexamethasone in the treatment of patients with relapsed/refractory multiple myeloma can achieve a sustained benefit in overall survival, and the safety is controllable
.

04Autologous dendritic cell immunotherapy combined with docetaxel and prednisone did not prolong overall survival in patients with metastatic castration-resistant prostate cancer.
Prostate cancer is the second leading cause of cancer-related death in older adults in Western countries
.

Although most patients initially benefit from androgen deprivation therapy, nearly all patients with advanced prostate cancer eventually progress to lethal castration-resistant prostate cancer (CRPC)
.

Before second-generation antiandrogens, the standard therapy for metastatic castration-resistant prostate cancer (mCRPC) was docetaxel plus prednisone
.

In contrast, prostate cancer has an immune desert-like phenotype, and immune checkpoint inhibitors have limited efficacy
.

DCVAC/PCa is a type of active cellular immunotherapy based on autologous dendritic cells (DCs) that activate anti-tumor immunity, enabling dendritic cells to acquire the ability to recognize cancer cells and act on human prostate cancer cells
.

Previous studies have shown that DCVAC/PCa can effectively improve the overall survival of patients, and it is well tolerated
.

On February 10, 2022, JAMA Oncol published the results of the VIABLE trial online, evaluating the efficacy and safety of DCVAC/PCa combined with docetaxel/prednisone in mCRPC
.

VIABLE is a multicenter, double-blind, placebo-controlled Phase 3 trial of patients with mCRPC who progressed after androgen deprivation therapy, randomized 2:1 to DCVAC/PCa and control
.

Patients in the DCVAC/PCa group received DCVAC/PCa combined with docetaxel/prednisone, and DCVAC/PCa maintenance therapy; patients in the control group received placebo combined with docetaxel/prednisone
.

The primary endpoint is overall survival, and secondary endpoints include progression-free survival and safety
.

A total of 1182 patients were enrolled in this trial, 787 patients were assigned to the DCVAC/PCa group and 395 patients were assigned to the control group, all of which were included in the efficacy analysis set
.

The results showed that the median overall survival was 23.
9 months (95% CI, 21.
6-25.
3) in the DCVAC/PCa group and 24.
3 months (95% CI, 22.
6-26.
0) in the placebo group, with no significant difference between the two groups.
(HR, 1.
04; 95% CI, 0.
90-1.
21; P = 0.
60)
.

About 70% of patients were abiraterone or enzalutamide naïve, and among patients naïve to abiraterone and enzalutamide, the median overall survival in the DCVAC/PCa arm was 26.
7 months ( 95% CI, 25.
2-28.
8) and 25.
7 months in the placebo group (95% CI, 23.
8-28.
3), with no significant difference between the two groups (HR, 0.
94; 95% CI, 0.
78-1.
13; P = 0.
50)
.

Among patients who had received abiraterone and/or enzalutamide, the median overall survival was 16 months (95% CI, 14.
7-18.
3) in the DCVAC/PCa group and 21.
0 months (95%) in the placebo group.
%CI, 17.
0-24.
1) (HR, 1.
28; 95% CI, 0.
98-1.
67; P = 0.
07)
.

In terms of safety, 677 patients (90.
4%) and 369 patients (97.
4%) in the DCVAC/PCa group and placebo group had at least one adverse event during treatment; the adverse events of grade 3 and above during treatment were There were 375 (50.
1%) and 216 (57.
0%) patients; treatment-related adverse event rates were 9.
2% and 12.
7%, respectively
.

The most common adverse events in the DCVAC/PCa group were fatigue (36.
2%), alopecia (29.
6%), and diarrhea (27.
5%)
.

In addition, there were 119 patients in this study who could not prepare DCVAC/PCa autologously.
The median overall survival of these patients was 18.
7 months, which was shorter than 23.
9 months in the DCVAC/PCa group.
The data of these patients may shorten the DCVAC/PCa group.
overall median overall survival
.

The unique highlight of this study is that it is a multi-center large-scale study that verifies the feasibility and universality of DCVAC/PCa treatment; secondly, the study shows that DCVAC/PCa treatment is well tolerated and safe, and no observed Systemic adverse reactions
.

mCRPC patients were treated with autologous dendritic cell immunotherapy DCVAC/PCa combined with docetaxel and prednisone, and DCVAC/PCa maintenance therapy was well tolerated and safe, but did not prolong the overall survival of patients; future needs To further clarify the predictors related to the efficacy of immunotherapy, in order to better select the population who can benefit from immunotherapy
.

05Clinical multivariate models can effectively predict the efficacy of immune checkpoint inhibitors in metastatic melanoma.
Immune checkpoint inhibitors can effectively improve the prognosis of patients with metastatic melanoma; however, according to the results of current melanoma studies, the 5-year overall survival rate The highest figure was 52% (combination of nivolumab and ipilimumab), that is, half of the patients still died of melanoma
.

In order to improve patient benefit, there is an urgent need to accurately identify patients who can benefit from immune checkpoint inhibitor monotherapy or combination therapy; and identify patients who are more inclined to receive targeted therapy or participate in clinical trials
.

Existing research evidence has demonstrated that several factors can predict the efficacy of immune checkpoint inhibitor therapy in metastatic melanoma, including tumor-related factors (such as tumor mutational burden, PD-L1 expression level, AJCC stage and serum lactate dehydrogenase level), Tumor microenvironment characteristics (such as tumor-infiltrating lymphocytes and interferon gamma expression levels), and host-level factors (such as gut microbiome and performance status)
.

These factors were generally isolated, only validated for association with overall survival, and were only studied in PD-1 or ipilimumab monotherapy cohorts, or could not be used in real-time for treatment decisions
.

On February 10, 2022, J Clin Oncol published online the results of Pires et al.
[5], which established an effective predictor of immune checkpoint inhibitor therapy with or without ipilimumab in metastatic melanoma.
A multivariate model of efficacy and survival that predicts response and survival outcomes in patients with metastatic melanoma treated with immunotherapy and can be a valuable tool for clinical decision-making
.

This study is a multicenter retrospective cohort study of metastatic melanoma with data from 1644 patients treated between December 2009 and April 2020
.

Demographics, disease characteristics, baseline blood analysis parameters, and response to PD-1 monotherapy or ipilimumab plus anti-PD-1 therapy were collected
.

Create models in discovery and validation cohorts to predict objective response rate, progression-free survival, and overall survival
.

 1644 patients were enrolled in three cohorts, the discovery cohort (n=633), validation cohort 1 (n=419) and validation cohort 2 (n=592)
.

The median follow-up time for the discovery cohort was 24.
0 months, the median follow-up time for the validation cohort 1 was 35.
4 months, and the median follow-up time for the validation cohort 2 was 27.
6 months
.

We first performed a univariate analysis in the discovery cohort to investigate the association between clinical factors (patient demographics, disease characteristics, and blood parameters) and objective response rates, and to develop a final predictive model, including patient performance status (ECOG performance status score), presence of lung and liver metastases, lactate dehydrogenase, neutrophil-lymphocyte ratio, and type and treatment modality
.

The area under the curve (AUC) for this model was 0.
71, from which we developed nomograms for the three prediction subgroups (good, moderate, and poor) and for comparison tests in the discovery and validation cohorts, internal and external Validation confirmed the consistency of this model
.

Using the same approach, the investigators created models for predicting progression-free survival and overall survival.
The progression-free survival model used the same factors as the objective response rate model (except for lung metastases), including the presence or absence of brain metastases and hemoglobin
.

The overall survival model was consistent with the factors included in the progression-free survival model
.

The three models performed similarly in first-line treated patients
.

To assist in choosing the most appropriate treatment, the researchers established a predictive model to analyze the response of anti-PD-1 monotherapy and ipilimumab combined with anti-PD-1 therapy, compared with anti-PD-1 monotherapy.
Response rates were significantly higher with ipilimumab combined with anti-PD-1 therapy
.

This is the first nomogram study in the world to accurately predict the efficacy of immune checkpoint inhibitors in metastatic melanoma based on a comprehensive analysis of clinicopathological factors before baseline treatment from a clinical perspective.
Drug therapy and/or combination therapy with ipilimumab provides the basis for selection
.

06Neratinib combined with fulvestrant in ER-positive/HER2-mutant metastatic breast cancer showed antitumor activity.
HER2 amplification/overexpression is a therapeutic target for breast cancer
.

However, most breast cancers do not have HER2 amplification/overexpression and are therefore not suitable for HER2-targeted drug therapy
.

With the advancement of tumor genome sequencing technology, recurrent HER2 mutations can be identified.
The mutation probability is about 2% in primary breast cancer and about 3% to 5% in metastatic breast cancer
.

HER2 mutations have been observed to be associated with poor prognosis in lobular breast cancer
.

Neratinib is an oral tyrosine kinase receptor inhibitor that inhibits HER2 and EGFR kinases, neratinib irreversibly binds to the HER-2 receptor and reduces autophosphorylation in cells, thereby reducing cancer proliferation of cells
.

In preclinical studies, endocrine therapy combined with neratinib produced a synergistic antitumor effect
.

Based on the hypothesis that the combination of neratinib and fulvestrant would be more effective, we conducted a single-arm, multi-cohort phase 2 trial in patients with ER+/HER2-mutated, non-amplifying metastatic breast cancer.
Published online on February 10, 2022 in Clin Cancer Res, the official journal of the American Society for Cancer Research[6]
.

In this study, patients were included in three cohorts, including an ER-positive fulvestrant-treated cohort and an ER-positive fulvestrant-naïve cohort, and a triple-negative breast cancer cohort
.

The fulvestrant-experienced and treatment-naïve cohorts received the combination of neratinib and fulvestrant, and the triple-negative breast cancer group received neratinib alone
.

The study objective was to evaluate the efficacy and safety of neratinib and fulvestrant in patients with ER+/HER2-mutated, non-amplifying metastatic breast cancer
.

The primary endpoint was clinical benefit rate
.

Between September 2015 and October 2020, a total of 40 patients were included in the study, fulvestrant-experienced cohort (n=24), fulvestrant-naïve cohort (n=11), and triple-negative breast cancer.
Cancer cohort (n=5)
.

A total of 35 patients were evaluable for efficacy (the three cohorts included 21, 10, and 4 patients, respectively)
.

The median progression-free survival of the fulvestrant-treated cohort was 24 weeks, and the clinical benefit rate was 38% (8/21), with 1 patient experiencing a complete response and 4 patients having a partial response
.

The median progression-free survival of the fulvestrant-naïve cohort was 20 weeks, the clinical benefit rate was 30% (3/10), and 3 patients experienced partial responses
.

The median progression-free survival in the triple-negative breast cancer cohort was 8.
5 weeks, the clinical benefit rate was 25% (1/4), and 1 patient experienced a complete response
.

Regarding safety, the most frequent study-related adverse events across all cohorts were diarrhea (85%), nausea (53%), fatigue (50%), anorexia (35%), and increased AST (28%)
.

The most common grade 3 adverse event was diarrhea (25%)
.

Other adverse events were mostly grade 1 and 2
.

No grade 4 adverse events occurred
.

No patient discontinued treatment due to adverse events
.

The results of this trial demonstrate that neratinib in combination with fulvestrant has antitumor activity in patients with metastatic ER-positive and HER2-mutated nonamplified breast cancer, regardless of prior CDK4/6 inhibitor treatment
.

In addition, sensitivity to neratinib may be influenced by breast cancer histology and location of HER2 mutation
.

The results of the MutHER study showed that the combination therapy of neratinib and fulvestrant showed antitumor activity in patients with ER-positive, HER2-mutated metastatic breast cancer with a manageable safety profile
.

Study data support further evaluation of dual HER2 blockade in metastatic breast cancer
.

References 1.
Schmid P, Cortes J, Dent R, et al.
Event-free survival with pembrolizumab in early triple-negative breast cancer.
N Engl J Med 2022;386:556-67.
2.
Tewari KS, Monk BJ, Vergote I, et al.
Survival with cemiplimab in recurrent cervical cancer.
N Engl J Med 2022;386:544-55.
3.
Richardson PG, Perrot A, San-Miguel J, et al.
Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study.
Lancet Oncol 2022 Feb 10.
DOI:10.
1016/S1470-2045(22)00019-5 (Epub ahead of print).
4.
Vogelzang NJ, Beer TM, Gerritsen W, et al.
Efficacy and safety of autologous dendritic cell-based immunotherapy, docetaxel, and prednisone vs placebo in patients with metastatic castration-resistant prostate cancer:The VIABLE phase 3 randomized clinical trial.
JAMA Oncol 2022 Feb 10.
DOI: 10.
1001/jamaoncol.
2021.
7298 (Epub ahead of print).
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Pires da Silva I, Ahmed T, McQuade JL, et al.
Clinical models to define response and survival with anti-PD-1 antibodies alone or combined with ipilimumab in metastatic melanoma.
J Clin Oncol 2022 Feb 10.
DOI:10.
1200/JCO.
21.
01701 (Epub ahead of print).
6.
Ma CX, Luo J, Freedman RA, et al.
al.
The phase II MutHER study of neratinib alone and in combination with fulvestrant in HER2-mutated, non-amplified metastatic breast cancer.
Clin Cancer Res 2022 Feb 10.
DOI: 10.
1158/1078-0432.
CCR-21-3418 (Epub ahead of print).
Copyright Information This article was translated, edited or commissioned by "NEJM Frontiers of Medicine" jointly created by Jiahui Medical Research and Education Group (J-Med) and "New England Journal of Medicine" (NEJM).
et al.
Clinical models to define response and survival with anti-PD-1 antibodies alone or combined with ipilimumab in metastatic melanoma.
J Clin Oncol 2022 Feb 10.
DOI:10.
1200/JCO.
21.
01701 (Epub ahead of print).
6.
Ma CX, Luo J, Freedman RA, et al.
The phase II MutHER study of neratinib alone and in combination with fulvestrant in HER2-mutated, non-amplified metastatic breast cancer.
Clin Cancer Res 2022 Feb 10.
DOI:10.
1158/1078-0432 .
CCR-21-3418 (Epub ahead of print).
Copyright Information This article was translated and written by NEJM Frontiers in Medicine, a joint collaboration between Jiahui Medical Research and Education Group (J-Med) and The New England Journal of Medicine (NEJM).
or make an appointmentet al.
Clinical models to define response and survival with anti-PD-1 antibodies alone or combined with ipilimumab in metastatic melanoma.
J Clin Oncol 2022 Feb 10.
DOI:10.
1200/JCO.
21.
01701 (Epub ahead of print).
6.
Ma CX, Luo J, Freedman RA, et al.
The phase II MutHER study of neratinib alone and in combination with fulvestrant in HER2-mutated, non-amplified metastatic breast cancer.
Clin Cancer Res 2022 Feb 10.
DOI:10.
1158/1078-0432 .
CCR-21-3418 (Epub ahead of print).
Copyright Information This article was translated and written by NEJM Frontiers in Medicine, a joint collaboration between Jiahui Medical Research and Education Group (J-Med) and The New England Journal of Medicine (NEJM).
or make an appointmentThe phase II MutHER study of neratinib alone and in combination with fulvestrant in HER2-mutated, non-amplified metastatic breast cancer.
Clin Cancer Res 2022 Feb 10.
DOI:10.
1158/1078-0432.
CCR-21-3418 (Epub ahead of print ).
Copyright Information This article was translated, written or commissioned by "NEJM Frontiers of Medicine" jointly created by Jiahui Medical Research and Education Group (J-Med) and "New England Journal of Medicine" (NEJM).
The phase II MutHER study of neratinib alone and in combination with fulvestrant in HER2-mutated, non-amplified metastatic breast cancer.
Clin Cancer Res 2022 Feb 10.
DOI:10.
1158/1078-0432.
CCR-21-3418 (Epub ahead of print ).
Copyright Information This article was translated, written or commissioned by "NEJM Frontiers of Medicine" jointly created by Jiahui Medical Research and Education Group (J-Med) and "New England Journal of Medicine" (NEJM). .

The full text of the Chinese translation and the included figures are exclusively authorized by the NEJM Group
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