The FDA has approved a new biweekly dosing regimen of 500 mg/m2 as a 120-minute intravenous infusion for cetuximab (Erbitux) for patients with KRAS wild-type, EGFR-expressing colorectal cancer (CRC) or squamous cell carcinoma of the head and neck (SCCHN).

With this regulatory decision, a biweekly dosing option is now available in addition to the weekly dosage regimen that had previously been approved for all approved indications when the agent is used either as a monotherapy or it is combined with chemotherapy.

The approval was based on findings from population pharmacokinetic modeling analyses that compared the predicted exposures of cetuximab delivered at a biweekly dose of 500 mg vs observed exposures in patients who received the agent at a weekly dose of 250 mg.

The application was also supported by data from pooled analyses of overall response rates, progression-free survival, and overall survival (OS) from published literature of cetuximab in patients with CRC and SCCHN. OS analyses that comprised real-world findings in patients with metastatic CRC who received either the weekly or biweekly dosing regimens was also used to support the decision.

In these exploratory analyses, the efficacy data proved to be consistent across dosage regimens examined and served to further support the data reported in the population pharmacokinetic modeling analyses.

The most common frequently reported toxicities with cetuximab include cutaneous adverse reactions such as rash, pruritus, and nail changes. Other adverse effects experienced with the agent include headache, diarrhea, and infection.

FDA approves new dosing regimen for cetuximab. News release. FDA. April 6, 2021. Accessed April 6, 2021. https://bit.ly/3mpj2Qj

Articles

The FDA has approved a new biweekly dosing regimen of 500 mg/m2 as a 120-minute intravenous infusion for cetuximab (Erbitux) for patients with KRAS wild-type, EGFR-expressing colorectal cancer or squamous cell carcinoma of the head and neck.

FDA Approves Additional Cetuximab Dose for KRAS Wild-Type, EGFR-Expressing CRC, Head and Neck Cancer

Tipifarnib showed promising clinical activity in patients with recurrent and/or metastatic, 

-mutant head and neck squamous cell carcinoma (HNSCC) whose disease had progressed after prior therapy, according to results from a phase 2, open-label, single-arm KO-TIP-001 trial (NCT02383927) published in the 

Among the 20 response-evaluable patients with a variant allele frequency (VAF) of 20% or higher (high VAF) treated on study, 11 met RECIST v1.1 criteria for confirmed partial response (PR), which translated to an objective response rate (ORR) of 55% (95% CI, 31.5%-76.9%). Tipifarnib resulted in a significant improvement in median progression-free survival (PFS) over last prior therapy received, at 5.6 months (95% CI, 3.6-16.4) and 3.6 months (95% CI, 1.3-5.2), respectively. Moreover, the median overall survival (OS) with tipifarnib was 15.4 months (95% CI, 7.0-29.7).

“We are encouraged by the compelling efficacy and safety profile of tipifarnib in patients with recurrent or metastatic 

-mutant HNSCC,” Alan Ho, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center and principal investigator of this trial, stated in a press release.

 “Importantly, these patients experienced limited benefit on prior therapies, including immunotherapies, which demonstrates the high unmet need for this disease. These data also reinforce the relevance of genomic testing for 

 mutations to identify patients who could potentially benefit from tipifarnib treatment.”

Despite recent advances in immunotherapy, the prognosis for patients with advanced HNSCC remains poor, and the development of biomarker-directed therapies in the recurrent and metastatic settings has been limited. Tipifarnib is a farnesyltransferase inhibitor that disrupts 

 function and has demonstrated durable anticancer activity in previous studies. In February 2021, the FDA granted a breakthrough therapy designation to tipifarnib for use in patients with recurrent or metastatic 

-mutated HNSCC with high VAF based on data from this trial that were presented during the 2020 ASCO Virtual Scientific Program.

This trial enrolled patients with incurable solid tumors that harbored missense 

 mutations; it was divided into 2 stages. The first stage was comprised of 3 cohorts, patients with thyroid cancer, those with non-thyroid solid tumors, and those with squamous cell carcinoma other than HNSCC. The second stage of the trial included those in cohort 2 who had HNSCC only; the cohort was expanded to further characterize safety and tolerability indications of interest.

A total of 31 patients were split into 2 subsets: those with 

 VAF of 20% or greater and serum albumin level of 3.5 g/dL or greater or 

 of 35% or greater (n = 22), and those with a 

 VAF of 20% or less or 20% to 35% with a serum albumin of 3.5 g/dL or less (n = 9).

To be eligible for enrollment on the trial, patients had to have 

-mutant disease with a VAF greater than 20%, measurable disease per RECIST v1.1 criteria that was relapsed/refractory to prior therapy, as well as an ECOG performance status of 0 or 1. Patients who had previously been treated with a farnesyltransferase inhibitor, who had a history of coronary heart disease, or who had uncontrolled brain, leptomeningeal, or epidural metastases were excluded.

Initially, oral tipifarnib was given to patients with HNSCC at a twice-daily dose of 900 mg on days 1 through 7 and 15 through 21 of 28-day cycles, based on data from 2 prior trials that established the safety of this schedule. However, of the first 15 patients dosed, 9 needed a dose reduction to manage adverse effects (AEs). As such, the median dose of tipifarnib by cycle 2 day 1 was 600 mg, given twice daily. The trial protocol was then amended to begin the agent at 600 mg twice daily to improve tolerability of tipifarnib and allow patients to continue on treatment for a longer period of time.

The primary end point of the trial was investigator-assessed ORR, while secondary end points included safety and tolerability. PFS, duration of response (DOR), overall survival, and feasibility of molecular analyses using next-generation sequencing were also evaluated as exploratory end points.

Among the 22 patients with high-VAF HNSCC, the median age was 63 years (range, 20-89), and the majority were male (68.2%). The primary location of the tumor was the oral cavity in 45.5% of patients (n = 10), and patients received a median of 2 prior treatments, which included platinum-based chemotherapy (90.9%), immunotherapy (63.9%), and cetuximab (Erbitux; 50%).

Additional results revealed that the ORR for the intent-to-treat population (n = 22) was 50% (95% CI, 30.7%-69.3%). Among the 20 evaluable high-VAF patients, those with a VAF of greater than 35% had an ORR of 58.3% vs 50% of t hose with a VAF that was less than 35%. Three of 12 patients with a VAF greater than 35% had an albumin of less than 3.5 g/dL with 1 (33.3%) experiencing response to the agent. Notably, responses were rapid, with 8 of 11 patients who met PR criteria experiencing response at the time of their first tumor assessment.

Moreover, 7 of 11 patients who achieved PRs ended up discontinuing treatment because of disease progression. Of the 9 patients who did not respond to tipifarnib, all achieved a best response of stable disease and 6 experienced minor tumor regression. Three of 9 patients who had disease stability received treatment for about 7 months, while 7 patients with PR continued treatment for at least 6 months.

Of the 11 patients who received immunotherapy as their last prior line of treatment, 7 experienced a PR and 4 achieved disease stability with tipifarnib. In the 8 patients who had a prior line of treatment that was not immunotherapy, 3 experienced PRs and 4 had stable disease.

The PFS benefit with tipifarnib proved to be greater in the patients who experienced a PR vs those who achieved stable disease, at 9.5 months (95% CI, 5.5-NA) vs 4.0 months (95% CI, 1.9-NA), respectively.

Safety was evaluated in 30 patients who were treated with tipifarnib. The most commonly reported treatment-emergent AEs (TEAEs) of any grade, irrespective of VAF or albumin cutoff, were hematologic, and included anemia, neutropenia, leukopenia, and lymphopenia. Gastrointestinal effects, such as nausea, were also reported.

Three patients reported TEAEs that led to discontinuation of tipifarnib: 2 patients had laryngeal obstruction and 1 had respiratory failure; however, these effects were not determined to be related to the study treatment. No treatment-related deaths were reported, and at data cutoff, no high-VAF participants had discontinued treatment due to AEs.

Tipifarnib will continue to be evaluated in the phase 2 AIM-HN/SEQ-HN trial (NCT03719690) in patients with 

"We are pleased to see our data from the phase 2 RUN-HN trial of tipifarnib published in the Journal of Clinical Oncology for review by the broader clinical community,” Troy Wilson, PhD, JD, president and chief executive officer of Kura Oncology, added in the release. "The highlighted data from the RUN-HN trial comes on the heels of our breakthrough therapy designation from the FDA and we continue to advance the ongoing AIM-HN registration-directed trial in patients with 

-mutant HNSCC, for whom there is an urgent unmet need.”

Ho AL, Brana I, Haddad R, et al. Tipifarnib in head and neck squamous cell carcinoma with 

. Published online March 22, 2021. doi:10.1200/JCO.20.02903

Kura Oncology announces publication of tipifarnib phase 2 data in Journal of Clinical Oncology. News release. Kura Oncology, Inc. March 22, 2021. Accessed March 24, 2021. 

Phase II study of tipifarnib in squamous head and neck cancer with HRAS mutations. ClinicalTrials.gov. Updated June 23, 2020. Accessed March 24, 2021. 

https://www.clinicaltrials.gov/ct2/show/NCT02383927

This article was originally published on OncLive as, "

Tipifarnib Showcases Encouraging Efficacy in Relapsed or Metastatic HRAS-Mutant HNSCC

Tipifarnib showed promising clinical activity in patients with recurrent and/or metastatic, HRAS-mutant head and neck squamous cell carcinoma whose disease had progressed after prior therapy.

Tipifarnib Promising in Relapsed/Metastatic HRAS-Mutant HNSCC

The FDA has granted a breakthrough therapy designation to tipifarnib for use in patients with recurrent or metastatic 

-mutated head and neck squamous cell carcinoma (HNSCC) with variant allele frequency (VAF) of 20% or higher following progressive disease on platinum-based chemotherapy.1

The decision is based on findings from the phase 2 RUN-HN trial (KO-TIP-001; NCT023383927) presented during the 2020 ASCO Virtual Scientific Program, in which tipifarnib elicited an objective response rate (ORR) of 50.0% (95% CI, 26.0%-74.0%) in response-evaluable patients with 

“We are very pleased that the FDA has awarded breakthrough therapy designation to tipifarnib, and we appreciate the agency’s affirmation of its potential to treat this devastating disease,” Troy Wilson, PhD, JD, president and chief executive officer of Kura Oncology, stated in a press release. “We remain focused on conducting our AIM-HN registration-directed trial and look forward to working closely with the FDA to bring this therapy to patients as soon as possible.”

The trial enrolled patients with solid tumors that harbored 

 mutations. The first stage of the trial comprised 2 cohorts: patients with thyroid cancer (n = 13) and patients with a solid tumor other than thyroid cancer (n = 13).

For the second stage of the trial, those in cohort 2 who had HNSCC moved into a HNSCC extension cohort, which could enroll up to 30 patients. Cohort 3 was also added, and this would enroll up to 20 patients with tumors other than HNSCC. Here, patients had to have a 35% or higher 

 VAF with serum albumin of 3.5 g/dL or higher.

To be eligible for enrollment, patients could not have any curative therapeutic option available to them, they had to have a tumor harboring a 

 mutation, measurable disease per RECIST v1.1 criteria, and an ECOG performance status of either 0 or 1.

In the second stage of the trial, patients were given oral tipifarnib at a twice-daily dose of 600 mg on days 1 through 7 and days 15 through 21 as part of 28-day treatment cycles.

The primary end point of the trial was ORR achieved with tipifarnib, while the secondary end point was safety and tolerability. Investigators examined progression-free survival (PFS) and duration of response (DOR) as exploratory end points.

A total of 21 patients were enrolled to the trial at the time of the presentation and 20 of them received treatment. Eighteen patients were determined to be evaluable for efficacy. The median age of study participants was 64 years, 66.7% were male, and in 52.4%, the primary tumor location was the oral cavity. Patients received a median of 2 previous anticancer regimens, and these treatments included platinum-based chemotherapy (90.5%), immunotherapy (61.9%), and cetuximab (Erbitux; 52.4%). Approximately 30% of patients were positive for human papillomavirus.

Additional results revealed that the median DOR with tipifarnib was 14.7 months. Moreover, the median PFS with the agent was 5.9 months (95% CI, 3.5-19.2), and the last previous line of treatment was 2.8 months (95% CI, 1.1-5.2). The median overall survival reported with tipifarnib was 15.4 months (95% CI, 7.0-46.4).

Tipifarnib is also under examination in the international, multicenter, open-label, 

 (KO-TIP-007; NCT33719690) in patients with 

-mutated HNSCC. Investigators seek to determine the ORR of tipifarnib in these patients; they will also retrospectively evaluate how the ORR to frontline treatment compares between the accrued patients with 

-mutated disease and matched-case control patients with 

The agent is also examination in patients with 

-mutated urothelial carcinoma (IST-01; NCT025335650).

Kura Oncology receives FDA breakthrough therapy designation for tipifarnib in head and neck squamous cell carcinoma. News release. Kura Oncology, Inc. February 24, 2021. Accessed February 24, 2021. 

Ho AL, Hanna GJ, Scholz CR, et al. Preliminary activity of tipifarnib in tumors of the head and neck, salivary gland and urothelial tract with HRAS mutations. 

. 2020;38(suppl 15):6504. doi:10.1200/JCO.2020.38.15_suppl.6504

FDA Grants Breakthrough Therapy Designation to Tipifarnib for HRAS-Mutated HNSCC

The FDA has granted a breakthrough therapy designation to tipifarnib for use in patients with recurrent or metastatic HRAS-mutated head and neck squamous cell carcinoma with variant allele frequency of 20% or higher following progressive disease on platinum-based chemotherapy.

Tipifarnib Gets Breakthrough Therapy Designation for HRAS-Mutated HNSCC

Nivolumab (Opdivo) in combination with chemotherapy as a frontline treatment demonstrated a significant survival benefit in patients with metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma, according to findings from the phase 3 CheckMate-649 trial (NCT02872116).

When compared with chemotherapy alone, the nivolumab combination met both primary end points of overall survival (OS) at a prespecified interim analysis of the trial, as well as progression-free survival at the time of the final analysis in patients whose tumors had PD-L1 expression with a combined positive score (CPS) of 5 or greater. Notably, the OS benefit achieved with the combination was also reported in the all-randomized patient population.

According to Bristol Myers Squibb (BMS), the developer of the agent, nivolumab is the first PD-1 inhibitor to show superior OS and PFS when used in combination with chemotherapy versus just chemotherapy alone in these patient populations. Moreover, the safety profiles observed with both nivolumab and chemotherapy in the trial were found to correlate with what has previously been reported with both approaches in the frontline treatment setting.

“There is an urgent need to improve therapeutic options for patients with esophageal and stomach cancer. Responses to the current standard chemotherapy in patients are short lived, and less than 6% of patients with metastatic disease survive beyond 5 years,” Yelena Y. Janjigian, MD, principal investigator and chief of Gastrointestinal Oncology at Memorial Sloan Kettering Cancer Center, stated in a press release. “Immunotherapy helped transform how we care for our patients across different tumor types, and the encouraging results from CheckMate-649 represent a new opportunity to improve survival for patients beyond standard chemotherapy.”

For patients with metastatic gastric or GEJ cancer, the frontline standard of care is a combination comprised of platinum and fluoropyrimidine, and the median OS achieved with this approach ranges from 8 months to 14 months.

Investigators hypothesized that nivolumab plus chemotherapy or ipilimumab (Yervoy) would result in stronger outcomes for patients with advanced or metastatic gastric/GEJ cancer over chemotherapy alone.

The goal of the multicenter, open-label, phase 3 trial was to compare the OS benefit achieved with nivolumab plus chemotherapy or nivolumab plus ipilimumab versus that of standard-of-care chemotherapy comprised of oxaliplatin and fluoropyrimidine in treatment-naïve patients with advanced or metastatic gastric/GEJ cancer and PD-L1&shy;—positive tumors.

To be eligible for participation, patients had to be 18 years of age or older and have advanced or metastatic gastric/GEJ cancer determined to be inoperable and predominant adenocarcinoma that was histologically confirmed.

 Patients also could not have received previous systemic treatment for advanced or metastatic disease and could not have had neoadjuvant or adjuvant treatment within the past 6 months. Moreover, to participate, they had to have an ECOG performance status ranging from 0 to 1 and they had to agree to provide a tissue sample so that investigators could determine their PD-L1 status.

Patients with known, untreated central nervous metastases, with active known or suspected autoimmune disease, grade 1 or higher peripheral neuropathy, HER2 positivity, a history of human immunodeficiency virus, or hepatitis B or C indicative of acute or chronic infection, were not permitted.

The primary end point of the trial was OS in participants with PD-L1—positive tumors, while key secondary end points included OS in all patients who underwent randomization, PFS in those whose tumors had PD-L1 positivity as well as all randomized patients, and time to symptom deterioration, which was evaluated via a GaCs questionnaire in both patients with PD-L1–positive tumors and all randomized patients.

For the trial, previously untreated patients with gastric/GEJ cancer were randomized to 1 of 3 treatment arms: 4 doses of nivolumab plus ipilimumab followed by nivolumab alone, nivolumab plus chemotherapy, either XELOX or FOLFOX, or XELOX or FOLFOX. All patients underwent post-treatment follow-up.

“The results from CheckMate-649, the largest study of gastric and esophageal cancers conducted to date, indicate the potential for [nivolumab] plus chemotherapy to change practice in the first-line setting and become a new standard of care for certain patients with gastric cancer, GEJ cancer, or esophageal adenocarcinoma,” Ian M. Waxman, MD, development lead of Gastrointestinal Cancers at BMS, added in the release. “We look forward to engaging health authorities worldwide with the goal of bringing this immunotherapy-based treatment option to patients as soon as possible.”

The pharmaceutical company plans to finish a full evaluation of the available data from the phase 3 trial, to work with investigators to present these data at an upcoming medical meeting, and to discuss the findings further with health authorities.

The company remains blinded to the data yielded in the nivolumab/ipilimumab arm and the trial will continue follow-up as planned to allow for the data to mature, according to BMS.

1. CheckMate-649, a phase 3 trial evaluating Opdivo (nivolumab) plus chemotherapy vs. chemotherapy, meets primary endpoints demonstrating superior overall survival and progression-free survival in first-line treatment of gastric and esophageal cancers. News release. Bristol Myers Squibb. August 11, 2020. Accessed August 11, 2020. https://bit.ly/3aompB2.

2. Chau I, Cleary JM, Feeney K, et al. CheckMate 649: a randomized, multicenter, open-label, phase III study of nivolumab (NIVO) + ipilimumab (IPI) or nivo + chemotherapy (CTX) versus CTX alone in patients with previously untreated advanced (Adv) gastric (G) or gastroesphageal junction (GEJ) cancer. J Clin Oncol. 2018;36(suppl 4):TPS192. doi: 10.1200/JCO.2018.36.4_suppl.TPS192

3. Efficacy study of nivolumab plus ipilimumab or nivolumab plus chemotherapy against chemotherapy in stomach cancer or stomach/esophagus junction cancer (CheckMate649). ClinicalTrials.gov. Updated June 17, 2020. Accessed August 11, 2020. https://clinicaltrials.gov/ct2/show/NCT02872116

This article was originally posted on OncLive as, "

Nivolumab Plus Chemotherapy Shows Significant Survival Benefit in Gastric and Esophageal Cancers

Nivolumab in combination with chemotherapy as a frontline treatment demonstrated a significant survival benefit in patients with metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

Nivolumab Plus Chemotherapy Improves Survival Outcomes in Gastric and Esophageal Cancers

On Friday, the FDA expanded the approval for Gardasil 9 for the prevention of oropharyngeal and other head and neck cancers caused by human papillomavirus (HPV) types 16,18,31, 33, 45, 52, and 58, according to Merck, the manufacturer of the vaccine.

According to the CDC, the majority (80%) of sexually active adults in the United States contract HPV within their lifetime. For most people, the virus clears up on its own, but for others, it can become cancerous — making vaccines like Gardasil 9 important.

While both men and women can contract HPV-related oropharyngeal cancer, the disease affects men 5 times more than women. Oropharyngeal cancer — the most prevalent type of HPV-related cancer in the United States – can be caused by an HPV infection in the oropharynx, which includes the soft palate, side and back wall of the throat, tonsils, and back third of the tongue.

“At Merck, working to help prevent certain HPV-related cancers has been a priority for more than two decades,” Alain Luxembourg, MD, director, clinical research, Merck Research Laboratories, said in a press release.

Gardasil 9 is already approved to prevent HPV-related cervical, vulvar, vaginal, and anal cancers, as well as dysplastic lesions and genital warts in females between the ages of 9 and 45. It is also approved for males between the ages of 9 and 45 to prevent HPV-related anal cancer or dysplastic lesions and genital warts.

Most common adverse events (AEs) in females (occurring in 10% or more of patients) were injection-site pain, swelling, erythema, and headache. For males, common AEs were injection-site pain, swelling, and erythema.

“Today’s approval for the prevention of HPV-related oropharyngeal and other head and neck cancers represents an important step in Merck’s mission to help reduce the number of men and women affected by certain HPV-related cancers,” Luxembourg said.

FDA Expands Gardasil 9 Approval for HPV-Related Cancers

Targeted therapy approvals in the last 10 years have changed the way oncology professionals treat patients with thyroid cancer, according to Marcia Brose, MD, PhD.

Brose, an associate professor of medicine and director of the Thyroid Cancer Therapeutics program at Penn Medicine at the University of Pennsylvania, had the chance to speak with 

, on the important updates in thyroid cancer. Brose also discussed the different treatment options in thyroid cancer after the use of targeted therapies.   

It's been an amazing last 10 years for thyroid cancer because we've had basically multiple FDA approvals, mostly with targeted therapies. So, after that, we also needed additional therapies because when those stopped working patients need other options. The big story in thyroid cancer is also a big story in other cancers.

And the first is the fact that track inhibitors actually play a role in thyroid cancer, maybe more significant than other cancers, because track fusion cancers are found anywhere up to 5 or maybe even a little bit more of differentiated thyroid cancer patients who are refractory to radioactive iodine. When that got approved, that's actually been a big positive thing for our patients because now we actually have options where patients have good therapeutic responses with very, very little side effects. A really good side effect profile.

Videos

The past 10 years have shown significant updates for treatment of patients with thyroid cancer, beyond just targeted therapies. 

Expert Discusses Updates in Thyroid Cancer

The FDA approved the use of single-agent pembrolizumab (Keytruda) for the treatment of recurrent, locally advanced or metastatic squamous cell carcinoma of the esophagus. Tumors must express PD-L1 (CPS 10 or higher) and have progressed after 1 or more lines of therapy, according to Merck, the manufacturer of the immunotherapy agent.

As new agents are approved in this space, the role of the oncology nurse will become increasingly important, according to Sarbajit Mukerjee, MD, MD, an assistant professor in the department of Medicine - GI Medical Oncology at Roswell Park Comprehensive Cancer Center. 

"Nurses always play a key role in the care of patients with squamous esophageal cancers, mostly related to teaching patients about their disease and symptom management related to the cancer and the treatments. With regards to pembrolizumab, there are some needed tests to establish whether these patients will be candidates for this therapy and there are some symptom and lab monitoring management issues associated with pembrolizumb therapy. For example we need to educate patients about and monitor their thyroid function as this can be impacted by pembrolizumab treatment," he said. 

The approval was based off the KEYNOTE-181 trial, a multicenter, randomized, open-label, active-controlled trial that showed that patients given pembrolizumab experienced improved overall survival (OS) compared to those on the chemotherapy arm.

“Historically, patients with advanced esophageal cancer have had limited treatment options, particularly after their disease has progressed,” said Jonathan Cheng, MD, vice president, oncology clinical research, Merck Research Laboratories, in a release.

The trial included 628 patients with recurrent or locally advanced or metastatic esophageal cancer who progressed on at least 1 other line of systemic therapy. Participants whose disease was HER2/neutral positive received treatment with an approved HER2/neu targeted therapy.

All patients on the trial had to have tumor specimens for PD-L1 testing, which was determined using the PD-L1 IHC 22C3 pharmDx kit. Patients were randomized by tumor histology — esophageal squamous cell carcinoma or esophageal adenocarcinoma/Siewert type I EAC of the gastroesophageal function – and geographic region.

In KEYNOTE-181, patients were randomized to receive either 200 mg of pembrolizumab every 3 weeks or investigators’ choice of any of the following intravenous chemotherapy regimens:

80-100 mg/m2 of paclitaxel on days 1, 8, and 15 of every 4-week cycle

Median OS on the pembrolizumab arm was 10.3 months compared to 6.7 months on the chemotherapy arm. Average progression-free survival (PFS) was 3.2 months (range, 2.1-4.4 months) for pembrolizumab and 2.3 months (range, 2.1-3.4) on the chemotherapy arm.

Pembrolizumab had an overall response rate (ORR) of 22%, a complete response rate (CRR) of 5%, and a partial response rate (PR) of 18%. All 3 of these numbers bested the chemotherapy arm, which had an ORR of 7%, CRR of 1%, and PR of 6%. Median duration of response was 9.3 months and 7.7 months for patients receiving pembrolizumab and chemotherapy, respectively.

Those given pembrolizumab who did not have disease progression could be treated for up to 2 years. Pembrolizumab treatment continued until disease progression or unacceptable toxicity. Severe or potentially fatal immune-related adverse events include: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis/renal dysfunction, skin reactions, solid organ transplant rejection, and complications with allogenic hematopoietic stem cell transplant. Practitioners should analyze the severity of reactions and decide if discontinuation of treatment or the administration of corticosteroids is most appropriate.

Findings from the KEYNOTE-180 trial also contributed to the FDA’s approval. This multicenter, non-randomized, open-label trial included 121 patients with locally advanced or metastatic esophageal cancer who progressed on 2 or more systemic therapies for their advanced disease. All other enrollment criteria were identical to KEYNOTE-181.

ORR in KEYNOTE-180 was 20% for patients with esophageal squamous cell carcinoma who had PD-L1 expression (CPS 10 or higher). Seven patients total responded to treatment. Among them, duration of response ranged from 4.2 to 25.1 months or more. Seventy-one percent (5 patients) had responses that lasted 6 months or longer, and 57% (3 patients) had responses that lasted 12 months or longer.

“With this approval, Keytruda is now the first anti-PD-1 therapy approved for the treatment of previously-treated patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10), providing an important new monotherapy option for physicians and patients in the United States,” Cheng said.

The FDA approved pembrolizumab to treat certain patients with recurrent, locally advanced or metastatic squamous cell carcinoma of the esophagus.

FDA Approves Pembrolizumab for Esophageal Cancer Subgroup

The role of the oncology nurse is vital when it comes to treating patients with head and neck cancer, explained Michael G. Moore, MD, director of head and neck surgery at Indiana University Health and president of the 

The nurses' role is critical. They're the ones who are literally right beside the patient the whole way through, not only with regard to talking to them about their treatment and administering it, but really supporting them along the way. Many people outside of just the physician take care of people, and nurses are one of the primary groups of people that really help support people, hold their hands, and also really provide them with the second-to-second and minute-to-minute advice and support along the way of their treatment. 

Nurses are there for patients every step of the way.

Oncology Nurses Are Key in Head and Neck Cancer Care

The FDA approved pembrolizumab (Keytruda) alone or in combination with platinum 5-fluorouacil (5-FU) chemotherapy for the frontline treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors are PD-L1 positive with a combined positive score (CPS) ≥1 according to Merck, the manufacturer of the immunotherapy agent.  

The approval was based off findings from the phase III KEYNOTE-048 trial, where single-agent pembrolizumab led to a significant improvement in overall survival (OS) compared to standard chemotherapy for patients whose tumors were PD-L1 positive with a CPS ≥20 and CPS ≥1. The immunotherapy agent also improved OS in the general population, too.

“This approval is a very exciting milestone in the treatment of head and neck cancer and has the potential to transform the way we treat patients with this debilitating disease by offering important new therapeutic options,” said Barbara Burtness, MD, professor of medicine, Yale School of Medicine and co-director, Development Therapeutics Research Program, Yale Cancer Center, in a statement. “Metastatic or recurrent head and neck cancer has been an area of significant unmet need, so it is encouraging to have immunotherapy regimens available for patients in the first-line setting.”

In the trial, single-agent pembrolizumab led to a 22% reduction in the risk of disease progression or death compared with the standard EXTREME regimen, which comprises cetuximab (Erbitux) with carboplatin or cisplatin plus 5-FU, in patients with PD-L1—positive tumors (HR, 0.78; 95% CI, 0.64-0.96; 

 = .0171). When in combination with chemotherapy in the overall KEYNOTE-048 population, the PD-1 inhibitor led to a 23% reduction in the risk of disease progression or death (HR, 0.77; 95% CI, 0.63-0.93; 

Patients enrolled on KEYNOTE-048 had squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. They did not have prior chemotherapy or systemic therapy, had a good ECOG performance status and tissue available for PD-L1 testing. Participants were stratified by PD-L1 expression, p16 status, and ECOG performance status.

Each patient was randomized to one of the following arms:

200 mg of pembrolizumab every 3 weeks, and carboplatin AUC 5 mg/mL/min every 3 weeks or 100 mg/m

 of FU a day as a continuous IV infusion over 96 hours every 3 weeks; or

/day of cetuximab as the initial dose, then 250 mg/m

once weekly, carboplatin AUC 5mg/mL/min IV every 3 weeks or 100 mg/m

/day of FU as a continuous intravenous infusion over 96 hours every three weeks (maximum of six cycles of platinum and FU)

Overall, pembrolizumab was well tolerated. The combination of pembrolizumab and chemotherapy had a comparable safety profile to EXTREME. The rates of grade 3 to 5 treatment-related adverse events (TRAEs) were 17% for those treated with pembrolizumab monotherapy and 69% for patients who received standard treatment. In the pembrolizumab/chemotherapy group, the rate of grade 3 to 5 TRAEs was 71%.

“Head and neck squamous cell carcinoma has historically presented many challenges to physicians and patients, including limited treatment options and physical and functional issues caused by the disease and its treatment,” said Jonathan Cheng, MD, vice president, clinical research, Merck Research Laboratories. “This approval is an important advance in the management of this devastating cancer. The results of KEYNOTE-048, which support this approval, demonstrated that Keytruda monotherapy for patients whose tumors expressed PD-L1 CPS greater than or equal to one and Keytruda in combination with chemotherapy regardless of PD-L1 expression significantly prolonged survival for patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma in the first-line setting.”

FDA Approves Alpelisib for Metastatic Breast Cancer

The FDA approved pembrolizumab alone or in combination with 5-FU to treat recurrent or metastatic head and neck squamous cell carcinoma.

FDA Approves Pembrolizumab Regimens for HNSCC

A patient's gender should not influence whether they are appropriate candidates for immunotherapy, according to study findings published in 

“When otherwise indicated, immunotherapy is likely to benefit men and women equally,” Christopher J. D. Wallis, MD, PhD, division of urology, University of Toronto, said in an interview with 

An earlier meta-analysis of randomized clinical trials showed that men derived 

 from immune checkpoint inhibitors compared with women, the researchers explained. To examine whether women have less advantage of this type of therapy, researchers investigated data from 23 different clinical trials that included 13,721 patients—9,322 (67.9%) men and 4,399 (32.1%) women&mdash;and most were in their 70s who had previously failed therapy.

 for metastatic cancers with other systemic treatment regimens, such as chemotherapy-based and targeted therapy, as well as immunotherapy-chemotherapy combinations compared with chemotherapy alone. The following cancer types were analyzed: non-small cell lung cancer (48%); melanoma (17%); clear cell renal cell carcinoma or small cell lung cancer (9%) each; and urothelial carcinoma, head and neck squamous carcinoma, mesothelioma, and gastric or gastroesophageal carcinoma (4%) each.

Overall survival in the first-line setting was evaluated in 11 of the trials. Most of the trials included therapy with a PD-1 or PD-L1 inhibitor and 6 trials (26%) used a CTLA-4 inhibitor, such as ipilimumab (Yervoy). The majority of the study designs included immunotherapy versus standard of care (SOC) and 6 trials included immunotherapy and SOC versus SOC alone.

No significant difference in treatment efficacy or overall survival between men and women were found, the researchers explained. “The study supports the use of immunotherapy for both men and women equally, when other was indicated,” Wallis said. “In contrast to prior hypothesis, it rejects the notion that women are less likely to benefit from immunotherapy.”

However, Wallis added that further exploration is needed based on the known differential autoimmune disease prevalence in women and men and in understanding how the immune system of men and women may respond to cancer and cancer therapies differently.

“There are many barriers to delivery of appropriate and efficacious health care,” Wallis said. “There was initially a suggestion that women may not benefit as much from immunotherapy as compared to men. Countering this message with data that women are likely to derive just as large a benefit should prevent any additional, gender-based barriers to immunotherapies which have proven, in many conditions, to be more effective than standard systemic therapies.”

Healthcare providers should not base cancer care with immune checkpoint inhibitors on gender, according to recent study findings.

Head and Neck Cancers