publication date: Oct. 4, 2019

Clinical Roundup

Adding targeted therapy drug to hormone therapy helps aggressive breast cancer patients live longer

Adding Kisqali (ribociclib) to standard hormone therapy significantly extended overall survival for postmenopausal patients with HR+/HER- advanced breast cancer in the phase III MONALEESA-3 trial.

The findings also show the combination treatment is beneficial with the longest time of recurrence today in first-line therapy, and should become a first-line option in postmenopausal women with HR+/HER2- advanced breast cancer.

Dennis Slamon, chair of hematology/oncology and director of Clinical/Translational Research at the UCLA Jonsson Comprehensive Cancer Center, presented the results Sept. 29 at the 2019 European Society for Medical Oncology Congress in Barcelona.

“Many people argue that the first type of treatment women with this type of metastatic cancer should receive is some other form of hormonal therapy and then wait to see if they respond to that treatment,” Slamon said in a statement. “But we found there’s a significant difference when you use the combination of ribociclib with hormone therapy as the first line of therapy. There is absolutely no reason to wait to give women this treatment. This should be the new standard.”

This is the second phase III trial where Kisqali combination therapy met the secondary endpoint of overall survival at the pre-planned interim analysis. MONALEESA-3 evaluated efficacy and safety of Kisqali plus fulvestrant in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer.

“Increasing overall survival is the hardest endpoint to move,” Slamon said. “We’re also seeing that the time of progression-free survival is the longest yet reported for any of the drugs in this class. And even when patients are off the drug, the effect seems to be long-lasting in terms of the benefit. It’s important because this means we are helping women live longer and have a better quality of life.”

The results on data previously reported by Slamon and colleagues helped lead to FDA’s approval of ribociclib. There are three CDK 4/6 inhibitors that have been approved by FDA for combination treatment with standard hormone therapies.

The double-blind clinical trial involved 726 postmenopausal women who had advanced hormone-receptor positive/HER2- breast cancer. The trial included women who had not received prior endocrine therapy as well as patients who were in the first-line or second-line setting.

The results demonstrated a statistically significant improvement in survival with a 28% reduction in risk of death. At 42 months, the estimated rates of survival were 58% for the drug combination treatment and 46% for women who were treated with the hormone therapy alone.

The median progression-free survival with ribociclib plus fulvestrant in the first-line setting is the longest reported in a phase III trial in hormone-receptor positive/HER2- breast cancer at a median of 33.6 months, compared to 19.2 months for those in the hormone therapy only group.

Kisqali in combination with fulvestrant met its secondary endpoint of overall survival, demonstrating a statistically significant improvement in survival with a 28% reduction in risk of death (median OS not reached vs. 40.0 months; HR=0.724; 95% CI: 0.568-0.924; p=0.00455).

The significant extension in survival met the early efficacy stopping criteria at a prespecified interim analysis. At 42 months, estimated rates of survival were 58% for Kisqali combination treatment and 46% for fulvestrant alone. Results in the first-line and second-line subgroups, including in patients who relapsed within 12 months of adjuvant treatment, were consistent with the overall MONALEESA-3 patient population.

Median first-line PFS was also reached at this analysis and demonstrated that Kisqali in combination with fulvestrant has a median PFS of 33.6 months compared to 19.2 months in the placebo arm (HR=0.546; 95% CI: 0.415-0.718). Additionally, the need for chemotherapy was delayed in all patients who were prescribed Kisqali plus fulvestrant (HR=0.696; 95% CI: 0.551-0.879).

Other investigators are Patrick Neven, Stephen Chia, Peter Fasching, Michelino De Laurentiis, Seock-Ah Im, Katarina Petrakova, Giulia Val Bianchi, Francisco Esteva, Miguel Martín, Arnd Nusch, Gabe Sonke, Luis De la Cruz-Merino, J. Thaddeus Beck, Xavier Pivot, Manu Sondhi, Yingbo Wang, Arunava Chakravartty, Karen Rodriguez-Lorenc, Guy Jerusalem.

The team is now evaluating these drugs in women with early-stage breast cancer in an international clinical trial called NATALEE.

The study was sponsored by Novartis, which developed ribociclib at the Novartis Institutes for BioMedical Research under a research collaboration with Astex Pharmaceuticals.


Opdivo + Yervoy demonstrate durable long-term survival benefits in advanced melanoma

The phase III CheckMate -067 trial continued to demonstrate improved overall survival with the first-line combination of Opdivo (nivolumab) plus Yervoy (ipilimumab), versus Yervoy alone, in patients with advanced metastatic melanoma.

Bristol-Myers Squibb sponsored the study.

With a minimum follow-up of 60 months, five-year overall survival rates were 52% for the Opdivo plus Yervoy combination, 44% for Opdivo alone, and 26% for Yervoy alone. Data from CheckMate -067 was presented at ESMO Sept. 28 and were simultaneously published in The New England Journal of Medicine.

The safety profile for Opdivo plus Yervoy was consistent with prior findings, with no new safety signals and no additional treatment-related deaths. At this five-year analysis, treatment-related adverse events were consistent with those previously reported and occurred in 300 (96%) patients in the combination group, 271 (87%) patients in the Opdivo group, and 268 (86%) patients in the Yervoy group. Grade 3/4 adverse events occurred in 186 (59%), 73 (23%), and 86 (28%) patients, respectively.

The percentage of patients experiencing an objective response remained stable at 58% for Opdivo plus Yervoy, 45% for Opdivo alone, and 19% for Yervoy, while the percentage of patients experiencing a complete response continued to increase, with complete response rates at five years of 22% for Opdivo plus Yervoy, 19% for Opdivo alone, and 6% for Yervoy alone. In addition, the proportion of patients alive and treatment-free was 74% in the Opdivo plus Yervoy group and 58% and 45% for Opdivo alone and Yervoy alone, respectively.

Among patients with BRAF-mutant or wild-type tumors, the rate of overall survival at five years was 60% and 48%, respectively, in patients who received Opdivo plus Yervoy; 46% and 43% for Opdivo alone; and 30% and 25% for Yervoy alone. Health-related quality of life continued to be maintained during or following treatment with Opdivo alone or the combination of Opdivo plus Yervoy.

“Now, with over half of patients treated with the nivolumab plus ipilimumab combination surviving to five years, and 74% of surviving patients remaining treatment-free, we have set a new and encouraging precedent,” CheckMate -067 lead investigator and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, James Larkin, said in a statement.

“The sustained long-term efficacy seen in the five-year CheckMate -067 data demonstrates the importance of dual Immuno-Oncology therapy,” development lead of Melanoma and Genitourinary Cancers at Bristol-Myers Squibb, Arvin Yang, said in a statement.

CheckMate -067 is a phase III, double-blind, randomized trial that evaluated the combination of Opdivo plus Yervoy or Opdivo monotherapy versus Yervoy monotherapy in 945 patients with previously untreated advanced melanoma. Patients in the combination group (n=314) received Opdivo 1 mg/kg plus Yervoy 3 mg/kg (Q3W) for four doses followed by Opdivo 3 mg/kg every two weeks (Q2W). Patients in the Opdivo monotherapy group (n=316) received Opdivo 3 mg/kg Q2W plus placebo. Patients in the Yervoy monotherapy group (n=315) received Yervoy 3 mg/kg every three weeks for four doses plus placebo. Patients were treated until progression or unacceptable toxic effects. Overall survival and progression-free survival were co-primary endpoints of the trial. Secondary endpoints included objective response rates, efficacy by tumor PD-L1 expression level and safety.


Data show improved OS with Jevtana over second AR-targeted agent in metastatic castration-resistant prostate cancer

Jevtana (cabazitaxel) demonstrated improved survival over second androgen receptor-targeted agent in patients with metastatic castration-resistant prostate cancer. The data were published Sept. 30 in The New England Journal of Medicine.

Patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and who progressed within 12 months on an androgen receptor (AR)-targeted agent (abiraterone or enzalutamide) experienced significantly longer radiographic progression free survival with Jevtana plus prednisone compared with abiraterone plus prednisone or enzalutamide.

Overall survival with Jevtana was also significantly longer. These findings from the CARD study were presented Sept. 30 at ESMO.

“In this study, treatment with Jevtana significantly improved radiographic progression free survival and overall survival compared with enzalutamide or abiraterone,” lead investigator on the CARD study, Ronald de Wit, of Erasmus MC University Hospital, Rotterdam, The Netherlands, said in a statement. “These  results are exciting as they have the potential to impact treatment guidelines for metastatic prostate cancer and current clinical practice.”

CARD is a randomized, open-label, treatment sequencing clinical study involving 62 sites across 13 European countries, enrolling 255 patients (median aged 70 years, 31% aged over 75 years) with mCRPC who were previously treated with docetaxel and who progressed within 12 months on an AR-targeted agent, in any order. These patients were randomized 1:1 to Jevtana (25 mg/m2 intravenously every three weeks, daily prednisone, and granulocyte colony-stimulating factor) versus abiraterone (1,000 mg plus prednisone, daily) or enzalutamide (160 mg daily; patients received abiraterone if they were previously treated with enzalutamide, or enzalutamide if they were previously treated with abiraterone).

The study’s primary endpoint was rPFS, which more than doubled with Jevtana treatment (N=129) compared to abiraterone or enzalutamide (N=126; median 8.0 vs 3.7 months; HR=0.54; 95% CI, 0.40–0.73; p<0.0001). Patients treated with Jevtana experienced an improvement in rPFS in all pre-specified subgroups, irrespective of the timing of the previous alternative AR-targeted agent, before or after docetaxel. Jevtana also significantly improved a key secondary endpoint, OS (median 13.6 vs 11.0 months; HR=0.64; 95% CI, 0.46–0.89; p=0.0078), reducing the risk of death from any cause by 36% compared with abiraterone or enzalutamide.

Other key secondary endpoints all favored Jevtana: progression free survival (median 4.4 vs 2.7 months; p<0.0001); confirmed prostate specific antigen (35.7% vs 13.5%; p=0.0002) and tumor responses (36.5% vs 11.5%; p=0.004). Pain response (45.0% vs 19.3%; p<0.0001) and time to symptomatic skeletal events (not reached vs 16.7 months; p=0.0499) were also significantly improved with Jevtana treatment.


TAILORx: New data on cohort with recurrence score 26-100 shows high cancer-free rate at five years

Estimated rate of freedom from recurrence of breast cancer at a distant site was 93% at five years, an outcome much better than expected with endocrine therapy alone, data from the TAILORx trial show.

TAILORx is the largest ever breast cancer treatment trial. The data reveal clinical outcomes with chemotherapy and includes a subset of 1,389 women with a high recurrence score of 26-100. The data, which were similar to outcomes in the B20 trial (Paik et al, JCO, 2006), were published in JAMA Oncology Sept. 30 and presented at ESMO.

The finding adds to the limited data on outcomes of patients with a high RS of 26-100, treated with taxane and/or anthracycline-containing chemotherapy regimens plus hormone therapy. It adds to the evidence base supporting the use of the Recurrence Score, a 21-tumor gene expression assay, to guide the use of adjuvant chemotherapy in early breast cancer.

TAILORx was designed and conducted by the ECOG-ACRIN Cancer Research Group with primary funding from the NCI.

“The initial results of TAILORx gave clinicians high-quality data to inform personalized treatment recommendations for women,” lead author, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System, and vice chair of the ECOG-ACRIN Cancer Research Group, Joseph A. Sparano, said in a statement.

“This new analysis provides the largest data set on outcomes in patients with early breast cancer and high recurrence score results. It confirms the importance of using the test to identify the minority of patients who will receive a significant benefit from adding adjuvant chemotherapy to endocrine therapy,” Sparano said.

Between 2006 and 2010, the TAILORx trial enrolled 10,273 women with hormone-sensitive, HER2-negative, axillary node-negative breast cancer at 1,182 sites in the United States, Australia, Canada, Ireland, New Zealand and Peru. Patients’ tumors were analyzed using the 21-tumor gene expression test and assigned a risk score (on a scale of 0-100) for cancer recurrence.

This analysis pertains to patients enrolled in TAILORx who had a score in the high-risk range (26 and above). These women were assigned to receive chemotherapy and hormone therapy following surgery. High-risk women were given the option to voluntarily join a prospective registry. Sufficient baseline and follow up information was available on 80% of these women (1,389 of 1,737) for inclusion in this analysis. There was a high adherence to chemotherapy assignment (94%).

Physicians were able to select one of several commonly used chemotherapy regimens. The majority of the patients (84%) received taxane and/or anthracycline-containing chemotherapy regimens. The most common regimens were docetaxel/cyclophosphamide (42%), anthracycline without taxane (24%), and anthracycline and taxane (18%). No chemotherapy was administered in 6% (non-adherence) and the regimen containing cyclophosphamide, methotrexate and 5-fluoruracil (CMF) was administered in 4%.

Clinical outcomes in TAILORx with chemotherapy and a high RS of 26-100 ranged by type of chemotherapy. Distant recurrence-free interval rates ranged from 92-96% at five years in patients treated with taxane and/or anthracycline therapy. The regimen containing cyclophosphamide, methotrexate and 5-fluoruracil had a DRFI rate of 89%.

The expected rates in TAILORx were based on the treatment effect of chemotherapy observed in B20: 79% at five years and 65% at nine years.

The genomic assay used in the trial was the Oncotype DX Breast Recurrence Score test from Genomic Health Inc.


Verzenio significantly extends life in HR+, HER2- advanced breast cancer patients

Verzenio (abemaciclib) in combination with fulvestrant significantly extended life by a median of 9.4 months in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer previously treated with endocrine therapy.

Lives were extended by a median of 46.7 months vs. median of 37.3 months with placebo plus fulvestrant; HR: 0.757; 95% CI: 0.606, 0.945; P = 0.0137. Eli Lilly and Company sponsors Verzenio.

Results from the phase III MONARCH 2 clinical trial, which included both pre/peri- and postmenopausal women, were consistent across subgroups. Researchers presented the results, simultaneously published in JAMA Oncology, Sept. 29 at ESMO.

In patients previously treated with endocrine therapy whose cancer quickly returned or spread to other parts of the body, or primary endocrine resistance, the results were consistent with the intent-to-treat population (HR: 0.686; 95% CI: 0.451, 1.043). Similar results were observed in women whose cancer spread to their organs, such as liver or lungs (also known as visceral disease; HR: 0.675; 95% CI: 0.511, 0.891).

Both of these analyses were pre-defined and results are consistent with ITT results from the MONARCH 2 study that had previously demonstrated a statistically significant improvement in the primary endpoint of progression-free survival, with overall survival as a secondary endpoint.

In addition to extending life, an exploratory analysis of these data has shown Verzenio in combination with fulvestrant delayed time to chemotherapy, with a median time to chemotherapy of 50.2 months versus 22.1 months in the placebo arm (HR: 0.625; 95% CI: 0.501, 0.779). In this exploratory analysis, patients who died before receiving chemotherapy were included up until the date of death. This finding may be an important treatment consideration in advanced breast cancer as physicians aim to postpone the use of chemotherapy for as long as possible.

“While CDK4 and 6 inhibitors have changed the way oncologists treat HR+, HER2- advanced breast cancer in the past few years, we are just beginning to understand which of these therapies meet the enormously important goal of significantly extending life in patients with advanced breast cancer,” Professor of medicine and breast oncology in the division of hematology/oncology at the University of Vermont Cancer Center, and MONARCH 2 study investigator Peter A. Kaufman, said in a statement.

“These important new findings from MONARCH 2 demonstrate further the benefits of Verzenio, and arm oncologists with additional information as they aim to optimize treatment for patients, including those whose cancer progressed following endocrine therapy,” Kaufman said in a statement.

The safety profile was consistent with primary analysis of MONARCH 2. No new safety signals were observed with long term follow-up (median of 47.7 months). At the time of analysis, 17% of patients in the Verzenio arm continued treatment versus 4% in the placebo arm.

These positive results demonstrated that Verzenio plus fulvestrant reached statistical significance at a pre-planned interim analysis. Lilly will continue to monitor patients enrolled in the trial. Any additional analyses will be considered post-hoc.

Lilly said it plans to submit overall survival data to global regulatory authorities. Verzenio in combination with fulvestrant is approved in more than 50 countries worldwide.

Additional data for investigational use of Verzenio presented at ESMO include positive results from the monarcHER trial, the first randomized clinical trial of a CDK4 & 6 inhibitor in combination with endocrine therapy versus standard-of-care chemotherapy for HR+, HER2+ patients, and positive results from MONARCH plus, the first trial of a CDK4 & 6 inhibitor in a predominantly Chinese population of women with HR+, HER2- advanced breast cancer.


Prospective trial uses blood-based NGS to identify those for treatment using Alecensa

The efficacy of Alecensa (alectinib) in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer, who were identified using liquid biopsy in the phase II/III BFAST study, is consistent with efficacy in those identified by tissue analysis in the phase III ALEX study.

Genentech, a member of the Roche Group, sponsors the BFAST trial. The BFAST trial was the first prospective study to use only blood-based next generation sequencing to detect specific fusions with the aim of selecting treatment for people with NSCLC, without the need for tissue biopsy. The positive results came from a single-arm cohort.

Results from the ALK cohort were presented at ESMO Sept. 30. 

“Obtaining tumor tissue for biomarker testing can be a challenge in many people with cancer and, as a result, some may not receive optimal treatment for their disease,” Sandra Horning, Chief Medical Officer and head of Global Product Development at Roche/Genentech, said in a statement. “BFAST is the first trial to show that by using a blood-based next-generation diagnostic, it is possible to identify the ALK mutation in people with non-small cell lung cancer using a blood draw alone, which means that more people could potentially benefit from Alecensa.”

Foundation Medicine partnered with Roche/Genentech on the study.

“Validated and comprehensive liquid biopsy tests are critical to help physicians find the best possible treatment approach for patients with advanced cancer and for whom tissue testing isn’t feasible,” Chief Medical Officer of Foundation Medicine, Brian Alexander, said in a statement. “Identifying ALK fusions can be particularly challenging and these data demonstrate that FoundationOne Liquid can accurately predict which patients can respond to therapy.”

The BFAST study used FoundationOne Liquid, Foundation Medicine’s liquid biopsy test, which detects the four main classes of genomic alterations, microsatellite instability and select fusions including ALK in circulating tumor DNA from a blood draw.

These data demonstrate that the FoundationOne Liquid assay can help test and identify a broader population of people with advanced NSCLC who may benefit from Alecensa, for whom current diagnostic tests are not suitable, such as for those who cannot provide tissue samples due to insufficient or absent tumor tissue, or where tissue diagnostics are not available, and validate the clinical utility of blood-based NGS as an additional method to inform clinical decision-making in ALK-positive NSCLC.

In the study, 87.4% (95% CI: 78.5-93.5) of people with advanced NSCLC who were identified by the FoundationOne Liquid biopsy assay to have ALK fusions had a confirmed response to treatment with Alecensa (overall response rate; ORR) as measured by the investigator per RECIST v1.1. This is consistent with the ORR for Alecensa observed in the pivotal phase III ALEX trial, which identified people using tissue-based testing.

When measured using an Independent Review Facility per RECIST v1.1, the confirmed ORR was numerically higher at 92.0% (95% CI: 84.1-96.7). Median progression free-survival and duration of response were not reached after a median follow-up of 12.6 months. The safety profile of Alecensa was consistent with prior clinical trials and post-marketing experience, with no new safety signals observed.


Tecentriq + platinum-based chemo improves PFS in untreated advanced bladder cancer

Tecentriq plus chemotherapy showed a statistically significant improvement in progression-free survival compared with platinum-based chemotherapy alone for the first-line initial treatment of patients with previously untreated locally advanced or metastatic urothelial carcinoma (mUC) eligible and ineligible for cisplatin chemotherapy.

Genentech, a member of the Roche Group, sponsored the phase III IMvigor130 study.

The median PFS of Tecentriq plus chemotherapy compared with platinum-based chemotherapy alone was 8.2 versus 6.3 months; [HR]=0.82, 95% CI: 0.70-0.96; p=0.007.

Encouraging overall survival results were observed for Tecentriq plus chemotherapy compared with chemotherapy alone in the intention-to-treat population, however these data did not reach statistical significance at this interim analysis (median OS=16.0 versus 13.4 months; HR=0.83, 95% CI: 0.69-1.00).

Safety in the Tecentriq plus chemotherapy arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.

“There remains a high unmet need for people with advanced bladder cancer, where chemotherapy alone is the current standard of care. These results reinforce the role of immunotherapy in treating this aggressive disease,” Chief Medical Officer and head of Global Product Development at Roche/Genentech, Sandra Horning, said in a statement.

Additional data from the Tecentriq monotherapy arm were also presented in the ITT population and people with different levels of PD-L1 expression. Encouraging OS results were observed with Tecentriq monotherapy in people with high PD-L1 expression (IC2/3), however these data were not formally tested per the hierarchical design of the trial. Follow-up will continue until the next analysis.

These data were presented at ESMO Sept. 30.

Tecentriq was the first cancer immunotherapy approved in advanced bladder cancer. Tecentriq has accelerated approval from tFood and Drug Administration for treatment of adults with locally advanced or mUC, including those who are not eligible for cisplatin-containing chemotherapy and whose tumors express high levels of PD-L1 (PD-L1–stained tumor-infiltrating immune cells covering ≥5% of the tumor area) as determined by an FDA-approved test or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

The accelerated approval also includes the treatment of adults with locally advanced or mUC whose disease had progressed during or following platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). These accelerated approvals are based on tumor response rate and durability of response. Continued approval in these types of bladder cancer may be contingent upon verification and description of clinical benefit in a confirmatory trial.

There are four ongoing phase III studies evaluating Tecentriq alone and in combination with other medicines in early and advanced bladder cancer. Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies, across lung, genitourinary, skin, breast, gastrointestinal, gynecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.


Pfizer reports positive data from late-stage BEACON CRC trial

Results from the phase III BEACON CRC trial show significant improvements in overall survival and objective response rates for the BRAFTOVI Triplet and BRAFTOVI Doublet combination (BRAFTOVI and cetuximab), compared to cetuximab plus irinotecan-containing regimens (Control), and provide analysis of the efficacy and safety of the BRAFTOVI Triplet compared to the BRAFTOVI Doublet.

The trial evaluates the combination of Braftovi (encorafenib), Mektovi (binimetinib), and cetuximab (Braftovi Triplet), in patients with advanced BRAFV600E-mutant metastatic colorectal cancer, following one or two lines of therapy.

Pfizer sponsors the trial.

BRAFTOVI Triplet showed a median OS of 9.0 months, compared to 5.4 months for Control. An improved ORR of 26% was observed in BRAFTOVI Triplet compared to 2% for Control.

These data were presented Sept. 30 at ESMO.

The company expects to submit the results of the trial for marketing approval in the United States in Q4 2019.


X4 reports positive data from phase IIa study of Mavorixafor + Axitinib in advanced clear cell RCC

Combination therapy with mavorixafor and axitinib (Inlyta) demonstrated clinical improvement with encouraging median progression free survival in a heavily pretreated advanced  clear cell renal cell carcinoma patient population.

The results come from the phase IIa portion of X4 Pharmaceuticals Inc.’s open-label phase I/II clinical trial of mavorixafor (X4P-001) in combination with approved tyrosine kinase inhibitor axitinib in patients with ccRCC.

Axitinib was generally well tolerated with a manageable safety profile. Of the 65 patients in the trial, 49 patients (or 75%) received mavorixafor + axitinib as a third- to ninth-line therapy, having received between two and eight prior therapies with a TKI, immuno-oncology agent, or other systemic therapy. Fifty-seven of the 65 patients in the trial (or 88%) had an intermediate or poor prognosis.

Data were presented Sept. 30 at ESMO.

Overall mPFS across clinically evaluable patients receiving mavorixafor + axitinib (n=62) was 7.4 months. Predefined subpopulations examined patients with immediate prior TKI and IO treatment. Patients treated in the subgroup with immediate prior TKI therapy (n=34) demonstrated an objective response rate (ORR) of 18% and an increased mPFS of 7.4 months.

This is a greater than 50% improvement from the 4.8-month historical mPFS with axitinib alone. Patients treated with mavorixafor + axitinib in the subgroup with immediate prior IO therapy (n=18) had an ORR of 61% and an increased mPFS of 11.6 months. In addition, eight of the 65 patients remain on the combination therapy today, with durations of treatment of 17 months or longer. Results suggest mavorixafor may enhance clinical response to axitinib and other TKIs that target tumor angiogenesis, as well as immunotherapy agents.

“In recent years a growing number of vascular endothelial growth factor (VEGF) TKI-based therapies (e.g., axitinib + pembrolizumab), have improved outcomes for patients with ccRCC. Despite these advances, most patients eventually develop resistance to therapy, and new treatment options are necessary to meet this unmet medical need,” lead investigator David F. McDermott, of Beth Israel Deaconess Medical Center, Harvard Medical School, said in a comment. “In this trial of mavorixafor, a novel CXCR4 pathway inhibitor, and axitinib in patients with metastatic ccRCC who had failed prior therapy, the combination was well tolerated and the anti-tumor activity was encouraging. We look forward to confirming the efficacy of mavorixafor in a randomized trial.”

This phase I/II, multi-center, open-label trial of mavorixafor in combination with axitinib included 65 patients with histologically confirmed advanced ccRCC, all of whom received at least one prior systemic therapy. The safety analyses included 65 patients from phases I/II who were treated with 400 mg mavorixafor (200 mg twice daily or 400 mg once daily) + 5 mg axitinib twice daily. Treatment responses were assessed using RECIST v1.1 (a validated set of criteria to assess changes in tumor burden), every eight weeks from day one for 80 weeks, and then every 12 weeks thereafter, by blinded, independent central review.


Half of cancer patients who enter tobacco treatment program quit smoking, study shows

Comprehensive tobacco treatment can help cancer patients quit and abstain from smoking, according to a study from MD Anderson Cancer Center.

The prospective study analyzed 3,245 smokers treated in MD Anderson’s Tobacco Treatment Program between 2006 and 2015. At three, six and nine-month follow-ups, smoking abstinence rates averaged 45%, 46% and 44%, respectively.

The study, described as the largest smoking cessation study of cancer patients to date, was published in JAMA Network Open Sept. 27.

Based on these findings, the authors advocate for full integration of comprehensive tobacco treatment into the oncological setting.

While the study was not designed as a randomized clinical trial and did not compare different types of smoking cessation programs, past studies have shown quitlines or other minimal interventions have abstinence rates of 20% or less. As with quitlines, abstinence rates for the Tobacco Treatment Program were self-reported and were not regularly biochemically verified.

“Patients deserve the absolute best opportunity we can give them to quit smoking,” lead author, Behavioral Science Chair and Director of the Tobacco Treatment Program Paul Cinciripini, said in a statement. “Based on our data, we recommend offering comprehensive smoking cessation to cancer patients as a clinical standard of care.”

MD Anderson’s program provides personalized tobacco treatment to nearly 1,200 new patients every year. Since 2013, patients have been automatically referred to the program through an electronic questionnaire used in all institutional clinics.

Program staff contact every new patient who self identifies as a smoker. Most patients who agree to participate in the comprehensive program receive both intensive counseling and proactive medication management.

“We tailor nicotine replacement therapy recommendations to each individual and provide support through behavioral counseling sessions over eight to 12 weeks following their initial consultation,” Professor of Behavioral Science and Medical Director of the Tobacco Treatment Program, Maher Karam-Hage, said in a statement. “Through this combined approach, we’ve seen effective results in cessation and abstinence.”

Cinciripini and Karam-Hage received grant support and medication (Chantix) from Pfizer to conduct smoking cessation trials, and have participated in two multisite trials sponsored by Pfizer.

Average cost per quit ranges from $1,900 to $2,500 at MD Anderson. Participants receive treatment services for free, as the Tobacco Treatment Program is funded primarily through Texas Tobacco Settlement Funds awarded through the Tobacco Master Settlement. The authors note this funding arrangement is progressive and could serve as a model for other states.

The MD Anderson program is open to employees as well. The study did not find a difference in abstinence rates between cancer patients and non-patients. For cancer patients, smoking also negatively impacts survival and treatment.

“Quitting at time of diagnosis increases the chance of survival by 30% to 40%. Patients also have less chance of a recurrence or secondary cancer if they quit. They will have fewer side effects and their treatments will be more effective. Longer term, they will enjoy a better quality of life,” said Assistant Professor of Behavioral Science Diane Beneventi.

This study received funding support from the State of Texas Tobacco Settlement funds and from MD Anderson’s Cancer Center Support Grant (CA016672).


Lynparza meets primary goal in late-stage study

Lynparza (olaparib) demonstrated statistically significant and clinically meaningful improvement in the primary endpoint of radiographic progression-free survival in certain tumors.

Lynparza reduced the risk of disease progression or death in the phase III PROfound clinical trial results by a median of 7.4 months versus 3.6 months for those receiving abiraterone or enzalutamide; Lynparza reduced the risk of disease progression or death by 66% for these men.

The drug is being developed by AstraZeneca and Merck.

The trial also met key secondary endpoint of rPFS in overall HRRm population, where Lynparza reduced the risk of disease progression or death by 51% and improved rPFS to a median of 5.8 months versus 3.5 months for those receiving abirateron or enzalutamide.

Secondary endpoint of median time to pain progression was not reached.

PROfound showed a confirmed overall response rate, a key secondary endpoint of 33.3% for Lynparza versus 2.3% for abiratone or enzalutammide in patients with BRCA1/2 or ATM mutations.

Safety and tolerability profile of Lynparza in the PROfound trial was in line with that observed in prior clinical trials.

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