The FDA approved nivolumab (Opdivo) for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy, according to Bristol Meyers Squibb — the agent’s manufacturer.

The agency based the priority review and approval on results from the multicenter, randomized, active-controlled, open-label global phase 3 ATTRACTION-3 trial — designed to evaluate nivolumab (n = 210), compared with taxane chemotherapy (docetaxel or paclitaxel; n = 209). The trial included patients regardless of tumor PD-L1 status.

Researchers randomized patients to receive either 240 mg IV nivolumab over 30 minutes every 2 weeks or investigator’s choice of taxane chemotherapy (either 75 mg/m2 IV docetaxel every 3 weeks [n = 65] or 100 mg/m2 paclitaxel once a week for 6 weeks followed by 1 week off [n = 144]). Patients were treated until disease progression or unacceptable toxicity.

Overall survival (OS) served as the primary end point. Secondary end points included investigator-assessed overall response rate (ORR) and progression-free survival (PFS), and duration of response (DOR).

In the trial, patients treated with Opdivo demonstrated superior median OS, compared with chemotherapy (10.9 months versus 8.4 months).

Researchers found no statistically significant difference in ORR (19.3% [95% CI, 13.7-26.0] vs 21.5% [95% CI, 15.4-28.8]; 

 = .6323) between the 2 arms. Among patients treated with nivolumab, 0.6% experienced a complete response and 18.7% with a partial response, compared with those treated with chemotherapy (1.3% and 20.3%, respectively).

Median PFD was 1.7 months (95% CI, 1.5-2.7) in the Opdivo arm, compared with 3.4 months (95% CI. 3.0-4.2) in the investigator’s choice chemotherapy arm (HR, 1.1; 95% CI, 0.9-1.3).

Safety was evaluated in 209 patients. Serious adverse events (AEs) occurred in 38% of patients given nivolumab, including pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. Fatal AEs consisted of interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

Treatment was discontinued in 3% of patients and was delayed in 27% of patients due to AEs.

The most common AEs, occurring in 20% or more of patients treated with nivolumab, included rash (22%) and decreased appetite (21%).

“Many cases of esophageal cancer are diagnosed at the advanced stage, when the disease could have a significant impact on a patient’s health. Treatment options can be limited once patients with advanced esophageal squamous cell carcinoma progress,” Adam Lenkowsky, general manager and head of US oncology, immunology and cardiovascular at Bristol Myers Squibb, said in a press release.

“The approval of Opdivo as a new treatment option for previously treated patients with advanced esophageal squamous cell carcinoma, regardless of PD-L1 expression, highlights our commitment to providing new options to address the unmet needs of patients and brings us another step closer to understanding the full potential of immunotherapy for gastrointestinal cancers,” he added.

Bristol Meyers Squibb. U.S. Food and Drug Administration Approves Opdivo® (nivolumab) for the Treatment of Patients with Advanced Esophageal Squamous Cell Carcinoma (ESCC) After Prior Fluoropyrimidine- and Platinum-based Chemotherapy. Published June 10, 2020. 

https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-approves-opdivo-nivolumab-trea

Articles

FDA Approves Nivolumab to Treat Advanced Esophageal Squamous Cell Carcinoma

 sat down with Brian Rini, MD, from the Vanderbilt-Ingram Cancer Center (VICC), to discuss results from the phase III TIVO03 trial, and its potential impact on patients with relapsed or refractory renal cell carcinoma.

As you know, there are several VEGF TKIs that are approved. So, the biggest advantage to tivozanib (Fotivda) is tolerability. It’s a very clean drug, hits VEGF pretty much, and has a very good tolerability profile in terms of side effects and need for dose interruption or reduction — which is very minimal. One thing where my mindset has changed now that we have immune therapy combinations that can be curative, is that when we are using single agent TKIs, we’re really just trying to control disease. Because we’re not curing those patients, and they can be on (TKI therapy) for many months or years, tolerability is really the key thing. I don’t think there are huge efficacy differences among TKIs. There are some – tivozanib was better than sorafenib in the TIVO-3 trial – but at the end of the day, in my opinion, it’s really more about tolerability.

Patients, appropriately, always want more options. I’ve never met a patient who doesn’t look down the road a little bit and say, “Gee doc, if this one doesn’t work, is there something else?” I totally get it. So, I think even though we on the physician side might say, “Do we really need another TKI?” From a patient standpoint, they absolutely want more options. Having a tolerable options, especially in this late line setting, is a potential advantage to patients. I often describe to patients that we’re just trying to get as many shots on goal as possible. You never know when one drug might work wonderfully or not at all. Even among the VEGF TKIs, they work differently in different patients for reasons I don’t think we understand. So, I think it adds to our weapons in this disease.

Videos

Oncology Nursing News sat down with Brian Rini, MD, from the Vanderbilt-Ingram Cancer Center (VICC), to discuss results from the phase III TIVO03 trial, and its potential impact on patients with relapsed or refractory renal cell carcinoma.

Tivozanib Tolerability Shows Potential Advantage for Patients with Advanced RCC

Integration of a comprehensive geriatric assessment with geriatrician-led management care improved health-related quality of life (HRQOL), unplanned hospital admissions, and treatment discontinuation among older adults undergoing systemic therapy for their cancer, according to results from the INTEGERATE study presented during a 2020 ASCO Virtual Scientific Program press briefing.

Of note, this is the first randomized study involving both geriatricians and oncologists for the care of older adults with cancer, according to the researchers.

“We found that oncogeriatric care in older people with cancer about to receive anti-cancer therapy led to significant improvements in health outcomes — at the patient level, quality of life, as well as the system level’s outcomes, such as hospital utilization and treatment delivery,” lead author Wee-Kheng Soo, MBBS, FRACP, a geriatrician and medical oncologist at Eastern Health in Melbourne, Australia, said during a pre-recorded presentation. “These findings suggest that those aged 70 or older with cancer should receive a geriatric clinical assessment to optimize their care and health outcomes.”

In the prospective, randomized, parallel-group, open-label study, those who received the intervention — which is a detailed systematic evaluation identifying medical, psychosocial, and functional limitations – had improved Elderly Functional Index (ELFI) scores, compared with those who received usual care across all follow-up points. However, the maximal difference in scores was seen at week 18 (estimated marginal mean ELFI score, 72.0 vs 58.7; 95% CI, 5.5-21.2; P = 0.001), but this was reduced by week 24 (estimated marginal mean ELFI score, 73.1 vs 64.6; 95% CI, 0.5-16.5; P = 0.037).

The intervention group also experienced improvements in functioning, mobility, burden of illness, and future worries, which persisted to the end of the study.

Moreover, the researchers saw an average of 1.3 fewer emergency room visits (39%) and 1.2 fewer unplanned hospital admissions per person per year (43%; P < .001), as well as a reduction in early treatment discontinuations (32.9% vs 53.2%; P = 0.01) among those who received intervention versus those who did not. Soo attributed the decline to be driven by reduced treatment-related toxicity and pointed out this could potentially be cost saving. Lastly, the number of overnight stays geriatric patients with cancer had decreased by 7 days per person per year (24%).

The trial included 154 patients aged >70 years with cancer planned for chemotherapy, targeted therapy, or immunotherapy. Patients were randomized 1:1 to receive either geriatrician-led comprehensive geriatric assessment and management integrated with usual care (n = 76) or usual care alone (n = 78).

HRQOL — the primary end point – consisted of physical, role and social functioning; mobility, burden of illness and future worries, and was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-ELD14 at 0, 12, 18, and 24 weeks. Secondary end points included function, mood, nutrition, health utility, treatment delivery, healthcare utilization, and survival.

The assessment was conducted through self-reported questionnaires and a comprehensive assessment by a geriatrician.

Thirteen patients died by week 12 and 130 (92.2% of the remaining patients) completed at least two primary outcome assessments.

“Currently, a person with cancer is typically referred to a geriatrician only in the later stages of their illness when they experience significant problems with completing everyday tasks,” the ASCO-issued release stated. “However, an integrated approach involving comprehensive geriatric assessment and early geriatrician involvement (also known as ‘integrated oncogeriatric care’) can help create a coordinated plan to optimize the older person with cancer.”

The researchers intend to implement the integrated comprehensive geriatric assessment in a large, multicenter implementation study comparing different care models in geriatric oncology and different cancer settings.

“The number of people worldwide over the age of 65 is expected to continue to grow, making the need for more rigorous research to help optimize the quality of care we provide to older patients an urgent priority. This study shows that geriatric assessments lead to clear improvements in quality of life and better care planning for older patients with cancer,” Howard A. Burris III, MD, FACP, FASCO, ASCO president, said in the release.

Soo WK. Integrated geriatric assessment and treatment (INTEGERATE) in older people with cancer planned for systemic anticancer therapy. Presented at: 2020 ASCO Virtual Scientific Program; May 12, 2020. Abstract 1201

ASCO press release. Integrating Geriatric Assessment and Management Into Cancer Care Improves Quality of Life, Reduces Hospital Admissions for Older Patients. Available from: https://www.asco.org/about-asco/press-center/news-releases/integrating-geriatric-assessment-and-management-cancer-care. Published May 13, 2020. Accessed May 13, 2020.

This article originally appeared on OncLive, titled “

Integrated Geriatric Assessment Optimizes Care for Older Adults with Cancer.

By integrating a comprehensive geriatric assessment with geriatrician-led management care researchers found an improved quality of life for older adults with cancer.
 

Integrated Geriatric Assessment Optimizes Care for Older Adults with Cancer

The FDA approved the combination use of encorafenib (Braftovi) and cetuximab (Erbitux) for the treatment of adult patients with 

-positive metastatic colorectal cancer (mCRC), as detected by an FDA-approved test, after prior therapy, according to Pfizer.

 mutations are estimated to occur in up to 15% of people with metastatic colorectal cancer and represent a poor prognosis for these patients,” lead study investigator Scott Kopetz, MD, PhD, FACP, associate professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, said in a press release. “As the first-and-only targeted regimen for people with BRAF

-mutant metastatic CRC who have received prior therapy, Braftovi in combination with cetuximab is a much-needed new treatment option for these patients.”

The approval is based on findings from the international open-label phase III BEACON CRC study, which were published in 2019 in the New England Journal of Medicine.

 The trial evaluated encorafenib plus cetuximab with or without binimetinib (Mektovi) in 665 patients with 

-positive mCRC whose disease had progressed after 1 or 2 prior regimens.

Patients were randomly assigned in a 1:1:1 ratio to the targeted therapy triplet of encorafenib, binimetinib, and cetuximab; the targeted therapy doublet of encorafenib and cetuximab; or the investigators’ choice of either cetuximab and irinotecan or cetuximab and FOLFIRI (folinic acid, fluorouracil, and irinotecan).

Results showed that the doublet demonstrated an improvement in overall survival (8.4 months [95% CI, 7.5-11.0] vs 5.4 months [95% CI, 4.8-6.6]; HR, 0.60; 95% CI, 0.45-0.79); 

 = .0003) objective response rates (20.0% [95% CI, 13.0%-29.0%] vs 2.0% [95% CI, 0.0%-7.0%]; 

 < .0001), and median progression-free survival (4.2 months [95% CI, 3.7-5.4] vs 1.5 months [95% CI, 1.4-1.7]; HR, 0.40; 95% CI, 0.31-0.52; 

 < .0001), compared with cetuximab plus irinotecan-containing regimens.

The most common adverse events (AEs; ≥ 25%) seen in patients treated with encorafenib in combination with cetuximab were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia and rash.

“We are pleased by the FDA’s approval of Braftovi in combination with cetuximab, as we are committed to developing targeted medicines that can help people living with certain mutation-driven cancers,” Chris Boshoff, MD, PhD, chief development officer of oncology at Pfizer Global Product Development, said in the release. “We are grateful to the patients and study investigators who participated in the phase III BEACON CRC trial and are proud to now be able to offer a targeted treatment option for people with BRAF

-mutant metastatic CRC who have received prior therapy. Looking ahead, we’re committed to continuing to investigate this treatment regimen across earlier lines of therapy.”

The FDA previously granted the triplet regimen a breakthrough therapy designation for the treatment of patients with BRAF

-mutant mCRC as detected by an FDA-approved test, following failure of 1 or 2 prior lines of treatment. Additionally, the triplet regimen has been included as a category 2A treatment for patients with BRAF

-mutant mCRC, following failure of 1 or 2 prior lines of therapy in National Comprehensive Cancer Network guidelines for colon and rectal cancers in the United States.

The ongoing phase II ANCHOR-CRC study (NCT03693170) is investigating the triplet as frontline treatment for patients with BRAF

1. U.S. FDA APPROVES BRAFTOVI® (ENCORAFENIB) IN COMBINATION WITH CETUXIMAB FOR THE TREATMENT OF BRAFV600E-MUTANT METASTATIC COLORECTAL CANCER (CRC) AFTER PRIOR THERAPY. Published April 8, 2020. https://www.pfizer.com/news/press-release/press-release-detail/u_s_fda_approves_braftovi_encorafenib_in_combination_with_cetuximab_for_the_treatment_of_brafv600e_mutant_metastatic_colorectal_cancer_crc_after_prior_therapy. Accessed April 8, 2020.

2. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. 

The FDA approved the combination use of encorafenib and cetuximab for the treatment of adult patients with BRAFV600E-positive metastatic colorectal cancer.
 

FDA Approves Encorafenib Plus Cetuximab for Metastatic CRC with BRAF V600E Mutation

The FDA granted full approval to pemetrexed (Pemfexy), a liquid injection and branded alternative to Alimta, for the treatment of patients with nonsquamous non-small cell lung cancer (NSCLC), according to Eagle Pharmaceuticals.

The injection is a ready-to-dilute formulation indicated for the following:

locally advanced or metastatic nonsquamous NSCLC in combination with cisplatin

locally advanced or metastatic nonsquamous NSCLC whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy, as maintenance treatment

locally advanced or metastatic nonsquamous NSCLC after prior chemotherapy as a single agent

malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery in combination with cisplatin

This conversion from tentative approval—granted in 2017, but at the time was not eligible for marketing in the U.S. because of existing patent protections&mdash;to final approval is followed by the company’s settlement agreement with Eli Lilly and Company, which allowed for the initial entry of pemetrexed for injection into the market on February 1, 2022, and a subsequent uncapped entry on April 1, 2022.

“We are pleased to receive final approval from (the) FDA and look forward to making Pemfexy available to the patients who can benefit. Our initial market exclusivity for PEMFEXY represents a significant opportunity for Eagle and builds on the successes of our expanding presence in the oncology space,” Scott Tarriff, chief executive officer of Eagle Pharmaceuticals, said in a press release.

With full approval, Eagle Pharmaceuticals has exclusive rights to commercialize the product for 4 months beginning February 1, 2022.

The agency granted full approval to pemetrexed for injection (Pemfexy), a liquid injection and branded alternative to Alimta, for nonsquamous NSCLC.
 

FDA Approves Pemetrexed for Injection for Nonsquamous Non-Small Cell Lung Cancer

The FDA granted a priority review to belantamab mafodotin for the treatment of heavily pre-treated patients with relapsed or refractory multiple myeloma, according to GlaxoSmithKline.

With this, belantamab mafodotin has potential to be the first anti-BCMA treatment available to patients.

The company based is biologics license application on data from the pivotal, open-label, two-arm, phase 2 DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study — designed to evaluate belantamab mafodotin in 293 patients with relapsed or refractory multiple myeloma with disease progression after 3 or more lines of therapy and who were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant (or both) to an anti-CD38 monoclonal antibody.

Patients demonstrated an overall response rate of 31% (97.5% CI, 20.8—42.6), with 30 of 97 patients experiencing a response to therapy. Of these responders, 18 achieved a very good partial response or better, including three patients with stringent complete or complete responses.

The median duration of response and overall survival have not been reached at 6 months of follow-up.

No new safety signals were seen. The safety and tolerability profile was consistent with previously reported data on belantamab mafodotin, with the 3 most commonly reported grade 3 or 4 edverse events including keratopathy (27%), thrombocytopenia (20%), and anemia (20%).

“Each day in my practice, I see patients who would benefit from additional therapeutic options because their disease has advanced and is no longer responding to available treatments,” principal investigator of the study, Sagar Lonial, MD, who is also chief medical officer at Winship Cancer Institute of Emory University and chair of the Emory Department of Hematology and Medical Oncology, said in a press release.

“In recent years, (B-cell maturation antigen [BCMA]) has become one of the most promising targets in multiple myeloma research,” he added. “The data…from DREAMM-2 not only reinforce the significance of BCMA as a potentially viable target, but also underscore the potential of belantamab mafodotin, if approved, as a practical treatment option in this patient population.”

1. GlaxoSmithKline. US Food and Drug Administration (FDA) grants priority review of belantamab mafodotin for patients with relapsed or refractory multiple myeloma. Available from: 

https://www.prnewswire.com/news-releases/us-food-and-drug-administration-fda-grants-priority-review-of-belantamab-mafodotin-for-patients-with-relapsed-or-refractory-multiple-myeloma-300990248.html?tc=eml_cleartime

2. Lonial S, Lee HC, Badros A. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. 

3. GlaxoSmithKline. Pivotal DREAMM-2 study demonstrated a clinically meaningful overall response rate with belantamab mafodotin (GSK2857916) for patients with relapsed/refractory multiple myeloma. Available from: 

https://www.gsk.com/en-gb/media/press-releases/pivotal-dreamm-2-study-demonstrated-a-clinically-meaningful-overall-response-rate-with-belantamab-mafodotin-gsk2857916-for-patients-with-relapsedrefractory-multiple-myeloma

The agency granted the immunoconjugate targeting B-cell maturation antigen priority review to belantamab mafodotin for the treatment of heavily pre-treated patients with relapsed or refractory multiple myeloma.
 

FDA Grants Priority Review to Belantamab Mafodotin for Relapsed/Refractory Myeloma

Oncoprex in combination with osimertinib (Tagrisso) received fast track designation from the FDA to treat patients with non-small cell lung cancer (NSCLC) with 

 mutations that progressed after treatment with osimertinib alone, according to Genprex, Inc., the immunogene therapy’s manufacturer.

"Genprex is excited to receive this important FDA designation," Rodney Varner, chairman and chief executive officer of Genprex, said in a press release. "In addition to potentially facilitating and expediting our pathway to approval, we believe that this FDA designation validates our plan to commercialize Oncoprex immunogene therapy in combination with 

 inhibitors for the treatment of lung cancer.”

Fast track designation is granted if the agency has determined that the drug demonstrates the potential to address unmet medical needs for a serious or life-threatening disease, with a goal of expediting drugs for these serious conditions. To received fast track designation, drugs must show an advantage over other available therapies. For example, the drug could be more efficacious in treating a particular patient population, or it could significantly reduce the side effects that patients are experiencing from treatment — ultimately improving diagnosis and outcomes.

With a fast track designation, Oncoprex is eligible for accelerated approval or rolling review of its biologics license application, and is also eligible for priority review if supported by clinical data at the time of the biologics license application submission.

“We hope that fast track designation helps us bring our gene therapy to patients more rapidly and that our unique gene therapy platform is more widely recognized for its potential in cancer treatment,” Varner added.

Genprex plans to initiate a phase I/II trial to evaluate the agent in combination with osimertinib, as well as a phase I trial to investigate Oncoprex plus a checkpoint inhibitor.

“Lung cancer is the world’s leading cause of cancer death, taking more lives each year than colon, breast and prostate cancers combined,” according to the release. “Each year, there are more than 2 million new lung cancer cases and 1.7 million deaths from lung cancer worldwide. In the United States, there are more than 228,000 new cases of lung cancer and more than 142,000 deaths from lung cancer each year. NSCLC represents 84% of all lung cancers, and the 5-year relative survival rate for metastatic lung cancer is less than 5%.”

Yahoo Finance. Genprex Receives U.S. FDA Fast Track Designation for Gene Therapy that Targets Lung Cancer. Available from: 

https://finance.yahoo.com/news/genprex-receives-u-fda-fast-130000971.html

Oncoprex in combination with osimertinib received fast track designation from the FDA to treat patients with non-small cell lung cancer.
 

FDA Grants Fast Track Designation to Oncoprex Combination for NSCLC

The FDA granted priority review to rucaparib (Rubraca) for the treatment of adult patients with 

-mutant recurrent, metastatic castration-resistant prostate cancer (mCRPC), according to Clovis Oncology, the drug’s manufacturer.

The agency set a Prescription Drug User Fee Act (PDUFA) date of May 15, 2020.

The application is based on findings from the ongoing, international, multicenter, open-label phase II TRITON2 trial that enrolled male patients with mCRPC associated with 1 of 13 homologous recombination repair (HRR) gene alterations.

Patients were treated with rucaparib at 600 mg twice daily until radiographic progression or treatment discontinuation.

The primary endpoints of the trial include confirmed ORR per RECIST/Prostate Cancer Clinical Trials Working Group 3 criteria in patients with measurable disease at baseline and PSA response in patients with no measurable disease at baseline.

Patients treated with the PARP inhibitor induced a 43.9% confirmed objective response rate (ORR; 95% CI, 24.4%-65.1%) by investigator assessment in 57 RECIST—evaluable patients with 

-mutant mCRPC. Among those with BRCA1/2 alterations, 51.1% had a confirmed PSA response to rucaparib. All 11 investigator-assessed radiographic responses in the patients with 

-mutated tumors were partial responses (PRs); 9 patients (36.0%) had stable disease. The median duration of response had not been reached.

The most common any-grade treatment-emergent adverse events occurring in >20% of patients were asthenia/fatigue (55.3%), nausea (49.5%), anemia/decreased hemoglobin (37.9%), decreased appetite (27.9%), transient increased aspartate transaminase/alanine aminotransferase (24.7%), constipation (24.7%), vomiting (22.1%), and diarrhea (21.1%).

Updated findings from the trial were presented at the 2019 ESMO Congress in September.

“Recently presented data suggests that Rubraca may play a meaningful role in the treatment of patients with 

-mutant recurrent, metastatic castrate-resistant prostate cancer, and this filing represents an important milestone for Clovis as it brings us one step closer to potentially making this valuable therapy available,” Patrick J. Mahaffy, president and CEO of Clovis Oncology, said in a press release. “We are encouraged by the FDA’s decision to grant priority review to the Rubraca application, which focuses on eligible patients with advanced prostate cancer, for whom new treatment options are very much needed.”

1. Clovis Oncology’s Rubraca (rucaparib) granted FDA priority review for advanced prostate cancer [news release]: Boulder, CO. Clovis Oncology, Inc. Published January 15, 2020. 

https://ir.clovisoncology.com/investors-and-news/news-releases/press-release-details/2020/Clovis-Oncologys-Rubraca-rucaparib-Granted-FDA-Priority-Review-for-Advanced-Prostate-Cancer/default.aspx

2. Clovis Oncology highlights Rubraca (rucaparib) updated data from the ongoing TRITON2 clinical trial in patients with mCRPC and exploratory and integrated analyses in recurrent ovarian cancer at the ESMO Congress 2019 [news release]: Boulder, CO. Clovis Oncology, Inc. Published September 29, 2019. 

https://ir.clovisoncology.com/investors-and-news/news-releases/press-release-details/2019/Clovis-Oncology-Highlights-Rubraca-rucaparib-Updated-Data-from-the-Ongoing-TRITON2-Clinical-Trial-in-Patients-with-mCRPC-and-Exploratory-and-Integrated-Analyses-in-Recurrent-Ovarian-Cancer-at-the-ESMO-Congress-2019/default.aspx

The FDA granted priority review to rucaparib for the treatment of adult patients with BRCA1/2-mutant recurrent, metastatic castration-resistant prostate cancer.
 

FDA Grants Priority Review to Rucaparib for BRCA1/2-Positive mCRPC

The FDA accepted and granted priority review to the supplemental biologics license application for nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of patients with metastatic or recurrent non-small cell lung cancer (NSCLC) with no 

genomic tumor aberrations, according to Bristol-Myers Squibb (BMS).

The agency set a Prescription Drug User Fee Act (PDUFA) goal date of May 15, 2020.

BMS based its supplemental biologics license application on data from part 1 of the multi-part, open-label phase III CheckMate -227 trial, designed to evaluate nivolumab in combination with ipilimumab, compared with chemotherapy, in patients with previously untreated NSCLC. In part 1, the researchers are evaluating 2 arms:

Nivolumab plus low-dose ipilimumab or nivolumab monotherapy versus chemotherapy in patients whose tumors express PD-L1 (part 1a)

Nivolumab plus low-dose ipilimumab or nivolumab plus chemotherapy versus chemotherapy in patients whose tumors express PD-L1 (part 1b)

In addition, part 2 of the study is evaluating nivolumab plus chemotherapy versus chemotherapy, regardless of PD-L1 status.

The co-primary endpoints in part 1 of the study were overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in part 1a) and progression-free survival (PFS) in patients with TMB ≥10 mut/Mb across the PD-L1 spectrum (assessed in patients enrolled across parts 1a and 1b).

The combination demonstrated significant improvement in OS versus chemotherapy alone. Moreover, the safety profile of the regimen was consistent with previously reported studies and no new safety signals were observed.

Part 2 did not meet its primary endpoint for OS for nivolumab plus chemotherapy versus chemotherapy alone, in patients with non-squamous NSCLC.

“The FDA’s acceptance of our application for Opdivo plus Yervoy represents an important milestone for patients with lung cancer in the United States, where, despite recent treatment advances, lung cancer remains the cause of more than 150,000 deaths each year,” Sabine Maier, MD, development lead of thoracic cancers at Bristol-Myers Squibb, said in a press release. “Lung cancer is the third tumor type where the combination of Opdivo and Yervoy has demonstrated significant long-term overall survival benefit in a randomized phase III trial, which further validates the immunologic rationale for dual immuno-oncology therapy.”

Bristol-Myers Squibb. U.S. Food and Drug Administration Accepts for Priority Review Bristol-Myers Squibb’s Application for Opdivo (nivolumab) Plus Yervoy (ipilimumab) in First-Line Non-Small Cell Lung Cancer. Available from: 

https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-accepts-priority-review-bris-1

The FDA accepted and granted priority review to the supplemental biologics license application for nivolumab in combination with ipilimumab for the first-line treatment of patients with metastatic or recurrent non-small cell lung cancer.
 

FDA Grants Priority Review to Frontline Nivolumab-Ipilimumab Combo for NSCLC

Trastuzumab deruxtecan (T-DXd; DS-8201) induced a confirmed objective response rate (ORR) of almost 61% and a durable benefit in heavily pretreated patients with advanced HER2-positive breast cancer, according to results from the phase II DESTINY-Breast01 trial presented at the San Antonio Breast Cancer Symposium, held December 10-14, in San Antonio, Texas.

ORR per independent central review (ICR) was 60.9% (95% CI, 53.4-68.0), including 11 complete responses (CRs; 6.0%), 101 partial responses (PRs; 54.9%), 67 with stable disease (SD; 36.4%), and 3 with progressive disease (PD; 1.6%). Two patients were not evaluable. ORRs were consistent across subgroups, including those with prior treatment with pertuzumab (Perjeta; 64%) and those with ≥ 3 prior regimens (59%).

These data present the potential of trastuzumab deruxtecan to establish a new standard of care for patients with advanced HER2 positive breast cancer,” Ian Krop MD, PhD, associate chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, said during a press briefing held at the meeting.

Moreover, the investigational HER2-targeted antibody-drug conjugate yielded a median duration of response (DOR) of 14.8 months (95% CI, 13.8-16.9), and a disease control rate (DCR) of 97.3% (95% CI, 93.8-99.1). Clinical benefit ratio at 6 months was 76.1% (95% CI, 69.3%-82.1%), and median time to response was 1.6 months (95% CI, 1.4-2.6 months). Activity of T-DXd across all major subgroups appeared consistent.

After a median follow-up of 11.1 months (range, 0.7-19.9 months), median progression-free survival (PFS) of 16.4 months (95% CI, 12.7-NE). Median PFS in the 24 patients with brain metastases was 18.1 months (95% CI, 6.7-18.1 months). Median overall survival was not reached (95% CI, NE-NE).

In the open-label, international, multicenter phase II registration study, investigators enrolled 253 patients with HER2-positive breast cancer who were heavily pretreated, including with T-DM1 (Kadcyla) and other HER2-targeted treatments. The trial consisted of part 1 to evaluate pharmacokinetics (n= 65) and to determine recommended dose (RP2D; n = 54) for part 2 (n = 134): 5.4 mg/kg T-DXd. Data from this study were published simultaneously in the New England Journal of Medicine.

ORR per ICR served as the primary endpoint. Secondary endpoints included DCR, DOR, and PFS.

Inclusion criteria included ≥18 years of age, unresectable and/or metastatic breast cancer, HER2-positive (centrally confirmed on archival tissue), prior T-DM1 therapy. Patients with a history of significant interstitial lung disease (ILD) were excluded. Those with stable, treated brain metastases were allowed.

All patients were female, the majority were white (55%), and 38% were Asian. Median age was 55 years (range, 28-96 years). Fifty-three percent were hormone receptor (HR)-positive and 45% were HR-negative. At baseline, the median number of prior treatment regimens was 6 (range, 2-27), including trastuzumab (Herceptin; 100%), T-DM1 (100%), pertuzumab (65.8%), and other HER2-targeted regimens (54.3%). The reported best response to T-DM1 before enrollment on the study were a CR and PR rate of 22%, 21% of patients with SD, and 36% with PD. Twenty-one percent were not evaluable.

As of the data cutoff (August 1, 2019), 79 patients (42.9%) are still on treatment, while 105 patients (57.1%) discontinued treatment, primarily for progressive disease (28.8%). In total, 184 patients enrolled on the study have received 5.4 mg/kg T-DXd for a median treatment duration of 6.9 months (range, 0.7-16 months).

Treatment-emergent adverse events (TEAE) occurred in 99% of patients, 51% being grade ≥ 3. The most common any-grade TEAEs were nausea (77%), alopecia (48%), fatigue (48%), vomiting (45%), constipation (34%), decreased neutrophil count (31%), decreased appetite (29%), diarrhea (27%), and anemia (26%). The most common grade ≥ 3 AEs were decreased neutrophil count (in 31% of the patients), nausea (7.6%), and anemia (in 26%).

Of note, 25 patients (13.6%) experienced ILD related to T-DXd by an independent adjudication committee. However, ILD was primarily grade 1 (2.7%) or 2 (8.2%). Median time to investigator-reported onset of ILD was 193 days (range, 42-535 days), and 13 of the 20 patients with grade ≥2 ILD received corticosteroids. Overall, 7 patients recovered, 2 were recovering at data cutoff, 12 were either outcome unknown or not followed until resolution, and 4 died. Of the 4 fatal cases, onset was from 63 to 148 days, of which 3 received steroids as part of their treatment, and death occurred 9 to 60 days after ILD diagnosis.

“(An independent) expert panel, after looking over this data (noted that in) future studies of trastuzumab deruxtecan patients (should) be monitored closely for symptoms of ILD, that trastuzumab deruxtecan be held, and the steroids started as soon as ILD is suspected,” Krop said.

T-DXd is a novel antibody drug conjugate that is comprised of 3 components: a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab; a topoisomerase I inhibitor payload, an exatecan derivative; and a tetrapeptide-based cleavable linker.

Phase I data, previously published in The Lancet Oncology, showed that T-DXd demonstrated an ORR of 59.5% (95% CI, 49.7-68.7) in patients with advanced HER-2 positive breast cancer previously treated with T-DM1.3 The FDA granted priority review to the agent in October.

“This is a fantastic result in heavily pretreated patients. If we move this treatment to earlier stage disease, I suspect the impact could be greater in these patients. This is great news for patients with HER2-positive breast cancer, concluded SABCS co-director and press briefing moderator Carlos Arteaga, MD, AACR past president and director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center.

1. Krop IE, Saura C, Yamashita T, et al. [Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) in subjects with HER2-positive metastatic breast cancer previouslytreated with T-DM1: A phase 2, multicenter, open-label study (DESTINY-Breast01). Presented at: the San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. Abstract GS1-03.      

2. Modi S, Saura C, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. NEJM. doi:10.1056/NEJMoa1914510.

3. Tamura K, Tsurutani J, Takahashi S, et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study

This article originally appeared on OncLive as, "

T-DXd Shows Potential to Establish New Standard of Care in Advanced HER2+ Breast Cancer

Trastuzumab deruxtecan had an ORR rate of nearly 61% for patients with advanced HER2-positive breast cancer.

Kristie L. Kahl