This document summarizes the results of a clinical trial investigating the efficacy and safety of pembrolizumab (anti-PD-1 antibody) in patients with advanced melanoma that progressed after treatment with ipilimumab. The overall response rate was 26% in the 2 mg/kg group and 10% in the 10 mg/kg group, with responses ongoing after 1 year. Pembrolizumab demonstrated a manageable safety profile, with grade 3-4 drug-related adverse events occurring in 12% of patients. This trial provides evidence that pembrolizumab is an effective treatment option for patients with advanced melanoma who have progressed on ipilimumab.
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Poly-ADP-ribose polymerase inhibitors (PARPis) are the most active and interesting therapies approved for the treatment of epithelial ovarian cancer. They have changed the clinical management of a disease characterized, in almost half of cases, by extreme genetic complexity and alteration of DNA damage repair pathways, particularly homologous recombination (HR) deficiency. It is causing a paradigm shift in the first-line treatment of patients with advanced ovarian cancer
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Join Dr. Kara Long Roche, Associate Director of the Gynecologic Oncology Fellowship Program at Memorial Sloan Kettering Cancer Center, as she breaks down new advancements in ovarian cancer research and treatment.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
What are the latest treatment advances for HER2-positive metastatic breast cancer? Eric Winer, MD, director of the Breast Cancer Program in the Susan F. Smith Center for Women's Cancers, discusses some of the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Join Dr. Kara Long Roche, Associate Director of the Gynecologic Oncology Fellowship Program at Memorial Sloan Kettering Cancer Center, as she breaks down new advancements in ovarian cancer research and treatment.
Report Back from San Antonio Breast Cancer Symposium (SABCS 2022)bkling
Curious about the latest developments in Early-Stage Breast Cancer and Metastatic Breast Cancer Research? Join us as Dr. Anne Blaes, the Division Director of Hematology/Oncology/Transplantation and Professor in Hematology/Oncology at the University of Minnesota, breaks down the most recent developments released at the annual San Antonio Breast Cancer Symposium regarding early-stage and metastatic breast cancer research.
Dr. Patrick Hwu presents the latest information on immunotherapies for melanoma at the MRF's Patient Symposium at MD Anderson Cancer Center on January 31, 2015.
Dana-Farber dermatologist Jennifer Lin, MD, discusses the latest research and treatment for melanoma.
This presentation was originally given as part of Dana-Farber's Tuesday Talks speaker series. In this talk, Lin provides an overview of melanoma, including recent research, progress and future goals.
Ballint syndrome : Q world Neurology Notes by Tanmay mehtaDr. Akruti Mehta
Ballint syndrome : Q world Neurology Notes by Tanmay mehta for PG medical Entrace exams like AIPGMEE , AIIMS , DNB , PGI and USMLE
Facebook.com/qworld.co.in
Neoadjuvant or adjuvant immunotherapy in melanoma stage iiiSameer Rastogi
The advent of neoadjuvant therapy in malignant melanoma might prove to be practice changing. Though still in research yet OPACIN and Neo OPACIN trials have unraveled the potential of neoadjuvant immunotherapy in malignant melanoma
ASCO 2015 Melanoma Immunotherapy
Thomas Olencki, DO Division of Medical Oncology Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus, Ohio
Edward B. Garon, MD, MS, Jamie E. Chaft, MD, and Matthew D. Hellmann, MD, prepared useful Practice Aids pertaining to lung cancer management for this CME/MOC/CE activity titled "Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Cancer Continuum: State of the Science and Implications for Practice." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2ATq0qp. CME/MOC/CE credit will be available until November 21, 2019.
Transitioning Survival from Months to Years in Advanced Non-Small Cell Lung C...H. Jack West
Dr. Jack West reviews the evolution of new treatment options for advanced NSCLC that have steadily improved survival. This progress has been incremental but now means that an ever-growing proportion of patients with advanced NSCLC have a realistic promise of potentially living several years after their diagnosis and the start of treatment. Note that this presentation does not address advances in immunotherapy, which were covered in a separate talk at the same conference at which Dr. West delivered this presentation.
Similar to Pembrolizumab in advanced melanoma (20)
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
Explore our infographic on 'Essential Metrics for Palliative Care Management' which highlights key performance indicators crucial for enhancing the quality and efficiency of palliative care services.
This visual guide breaks down important metrics across four categories: Patient-Centered Metrics, Care Efficiency Metrics, Quality of Life Metrics, and Staff Metrics. Each section is designed to help healthcare professionals monitor and improve care delivery for patients facing serious illnesses. Understand how to implement these metrics in your palliative care practices for better outcomes and higher satisfaction levels.
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
Join us as we delve into the crucial realm of quality reporting for MSSP (Medicare Shared Savings Program) Accountable Care Organizations (ACOs).
In this session, we will explore how a robust quality management solution can empower your organization to meet regulatory requirements and improve processes for MIPS reporting and internal quality programs. Learn how our MeasureAble application enables compliance and fosters continuous improvement.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
According to TechSci Research report, "India Clinical Trials Market- By Region, Competition, Forecast & Opportunities, 2030F," the India Clinical Trials Market was valued at USD 2.05 billion in 2024 and is projected to grow at a compound annual growth rate (CAGR) of 8.64% through 2030. The market is driven by a variety of factors, making India an attractive destination for pharmaceutical companies and researchers. India's vast and diverse patient population, cost-effective operational environment, and a large pool of skilled medical professionals contribute significantly to the market's growth. Additionally, increasing government support in streamlining regulations and the growing prevalence of lifestyle diseases further propel the clinical trials market.
Growing Prevalence of Lifestyle Diseases
The rising incidence of lifestyle diseases such as diabetes, cardiovascular diseases, and cancer is a major trend driving the clinical trials market in India. These conditions necessitate the development and testing of new treatment methods, creating a robust demand for clinical trials. The increasing burden of these diseases highlights the need for innovative therapies and underscores the importance of India as a key player in global clinical research.
1. Journal Club
Ranjita Pallavi
Fellow 1
Department of Hematology/Oncology
Westchester Medical Center
2. Introduction
• Despite recent advances such as the anti-cytotoxic T-lymphocyte-associated-
antigen-4 (CTLA-4) antibody ipilimumab and the mitogen-activated
protein kinase pathway inhibitors vemurafenib, dabrafenib,
and trametinib, melanoma treatment remains a challenge because
there are few effective treatment options for patients who relapse or
do not respond to these therapies.
3. Introduction
• Response has been reported in about 25% and 50% of patients
treated with MEK and BRAF inhibitors, respectively, and these agents
are associated with a survival advantage compared with
chemotherapy.
• However, their use is restricted to the roughly 50% of patients
with BRAF V600-mutant melanoma, and the median duration of
response is about 6–7 months.
• Combination therapy with BRAF and MEK inhibitors results in an
objective response rate of 76% and extends progression-free survival
(PFS), but most patients develop resistance to these inhibitors.
4. Introduction
• Thus, there was an urgent need to develop effective treatment
options for patients who progress on these agents.
• The distinct mechanism of action of anti-programmed-death-receptor-
1 (PD-1) antibodies, which increase tumour cell killing
peripherally by cytotoxic T lymphocytes, might have activity in
patients with ipilimumab-refractory melanoma.
• The programmed death 1 (PD-1) receptor is a negative regulator of T-cell
effector mechanisms that limits immune responses against
cancer.
5. Anti PD-1 Mechanism of action
Nat Immunol. 2013 Dec;14(12):1212-8.
A rheostat for immune responses: the unique properties of PD-
1 and their advantages for clinical application.
Okazaki T et al.
6. Anti PD-1/CTLA4 Mechanism of action
Nat Immunol. 2013 Dec;14(12):1212-8.
A rheostat for immune responses: the unique properties of PD-1 and
their advantages for clinical application.
Okazaki T et al.
7. Anti PD-1 Mechanism of action
• PD-1 is expressed on antigen-stimulated T cells and induces
downstream signaling that inhibits T-cell proliferation, cytokine
release, and cytotoxicity.
• Many tumors, including melanoma, suppress cytotoxic T-cell
activity by expressing PD-1 ligand (PD-L1) on the cell surface.
• Anti-PD-1 and PD-L1 antibodies can reverse this T-cell suppression
and induce long-lasting antitumor responses in patients with
advanced solid tumors, including advanced melanoma.
8. Anti PD-1 (Pembrolizumab)
• Pembrolizumab (MK-3475, previously known as lambrolizumab) is a
highly selective, humanized monoclonal IgG4-kappa isotype antibody
against PD-1 that has shown robust clinical activity with an acceptable
safety profile.
• In 135 patients with advanced melanoma who were enrolled in non-randomized
cohorts of the large, phase 1 study KEYNOTE 001,
pembrolizumab resulted in long-lasting objective responses in 31–
51% of patients treated with doses ranging from 2 mg/kg every 3
weeks to 10 mg/kg every 2 weeks, and 81% of patients survived for at
least 1 year after starting treatment.
9. Anti PD-1 (Pembrolizumab)
• Of note, promising antitumor activity and acceptable safety were
noted in the 48 patients previously treated with ipilimumab.
• However, the sample size was insufficient to assess clinical benefit
accurately, and lack of randomization between doses and schedules
restricted the ability to assess a dose-response relation.
• In this study, an expansion cohort of KEYNOTE-001, were assessed
further for the clinical benefit of pembrolizumab in patients whose
advanced melanoma progressed after ipilimumab and who were
previously treated with a BRAF or MEK inhibitor, or both, a clinical
scenario for which there is no effective treatment.
10. Anti PD-1 (Pembrolizumab)
• The study was done to compare the efficacy and safety of
pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in
patients with ipilimumab-refractory advanced melanoma.
11. Methods
• This trial was a multicentre, international (Australia, Canada, France,
and the USA), randomized expansion cohort of the phase 1 KEYNOTE-
001 study.
12. Inclusion Criteria
• Patients aged 18 years or older.
• Patients with progressive, measurable and unresectable melanoma
that was previously treated with at least two doses of ipilimumab 3
mg/kg or higher administered every 3 weeks.
• Those who had confirmed disease progression using immune-related
response criteria within 24 weeks of the last dose of ipilimumab
• Patients who had adequate performance status and organ function.
• Resolution of all ipilimumab-related adverse events to grade 0 to 1
was required.
13. Inclusion Criteria
• Previous treatment with approved BRAF or MEK inhibitors, or both,
was required for patients with BRAF -mutant melanoma.
• There were no limitations on the number of previous treatments.
• Patients were not screened for brain metastases at baseline, and
those with previously treated brain metastases were eligible if there
was no evidence of CNS progression for 8 weeks.
14. Exclusion Criteria
• Previous treatment with a PD-1 or PD-L1 blocking agent.
• Use of current systemic immunosuppressive therapy.
• Active infection.
• Autoimmune disease.
• Patients with a history of grade 4 immune-related adverse events
requiring steroid treatment or grade 3 immune-related adverse
events requiring steroid treatment with prednisone at doses greater
than 10 mg/day or equivalent for more than 12 weeks.
15. Methods
• Primary endpoint was overall response rate (ORR) assessed with the
Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) by
independent central review.
• ORR was also assessed according to immune-related response
criteria by the investigator.
• The definition of ORR was the percentage of patients who achieved a
best overall response of confirmed complete or partial response.
16. Methods
• Secondary endpoints were response duration (ie, time from best
overall response of partial or complete response to time of first
documented disease progression), PFS (ie, time from treatment
initiation to time of first documented disease progression or death
due to any cause), and overall survival (ie, time from treatment
initiation to death due to any cause).
17. Methods
• Tumor response was assessed every 12 weeks after pembrolizumab
initiation, with patients managed according to immune-related
response criteria per investigator.
• Adverse events were assessed continuously and were graded
according to the National Cancer Institute Common Terminology
Criteria for Adverse Events.
18. Methods
• A mandatory baseline biopsy specimen was obtained from each
patient for biomarker assessment.
• Peak and trough blood samples were obtained from patients at
treatment initiation for pharmacokinetic analysis.
• Additional trough samples were gathered roughly every 12 weeks for
the first 12 months on the study and every 6 months thereafter.
• Pembrolizumab serum concentrations were quantified with a
validated electrochemiluminescent assay (lower limit of
quantification 10 ng/mL).
20. Baseline Characteristics
• Patients were heavily pretreated, with
125 (72%) receiving at least two and
60 (35%) receiving at least three
previous treatments including
ipilimumab.
21. Results
• The mean interval between the last dose of ipilimumab and the first
dose of pembrolizumab was 33·4 weeks (range 4·0–173·0) in the
pembrolizumab 2 mg/kg group and 34·1 weeks (6·0–248·0) in the
pembrolizumab 10 mg/kg group.
• Median follow-up was 8 months with all patients having at least 6
months of follow-up.
• At analysis, 73 (42%) of 173 patients were still on treatment.
• The most common reason for discontinuation of treatment was
disease progression (59 [34%] of 173).
22. Results
• ORR was 26% in the pembrolizumab 2 mg/kg (21 of 81 patients) and
10 mg/kg groups (20 of 76 patients; p=0·96).
• 59 (73%) patients in the pembrolizumab 2 mg/kg group and 52 (68%)
in the 10 mg/kg group had a reduction from baseline in target lesion
size.
23. Results
• Median response duration was not reached in either dose group at
the time of analysis (range >6 weeks to >37 weeks), with 36 (88%) of
41 responders alive with no other anticancer treatment and with non-progressive
disease by independent central review.
• Analysis of time to response indicates that although most responses
to pembrolizumab occurred by week 12, responses might also occur
late in the course of treatment, with responses noted as late as 36
weeks after treatment initiation.
24. Results
• Exploratory analysis showed that response rates were mostly similar
in the major subgroups.
• ORR in the BRAF -wild-type subgroup of 131 patients (28%, 95% CI
20–36) was higher than in the BRAF -mutant subgroup of 26 patients
(19%, 7–39). Of note, the 95% CIs for these subgroups overlapped.
26. Results
• The survival analysis was
updated in May, 2014.
• The HR for the difference
in overall survival
between the treatment
groups was 1·09 (95% CI
0·68–1·75).
• The Kaplan-Meier
estimated overall survival
at 1 year (proportion of
patients alive at 1 year)
was 58% (95% CI 47–68)
in the pembrolizumab 2
mg/kg group and 63%
(51–72) in the
pembrolizumab 10 mg/kg
group.
27.
28. Results
• Pembrolizumab was generally well tolerated.
• Overall, the safety profiles were similar between the pembrolizumab 2 mg/kg and 10 mg/kg
groups.
• Drug-related adverse events occurred in 73 (82%) patients in the pembrolizumab 2 mg/kg group
and 69 (82%) in the pembrolizumab 10 mg/kg group.
• However, drug-related grade 3 or 4 adverse events occurred in only 20 (12%) patients, and the
only drug-related grade 3 to 4 adverse event that occurred in more than one patient was fatigue
(five [3%]).
• The most common drug-related adverse events of any grade were fatigue, pruritus, and rash.
• Grade 3 or 4 immune-mediated adverse events occurred in only three patients: autoimmune
hepatitis, maculopapular rash, and pancreatitis.
• Potentially immune-mediated adverse events were generally manageable with treatment
interruption and corticosteroid treatment, with only four patients discontinuing because of
adverse events that were immune related.
29. Discussion
• The anti-PD-1 antibody pembrolizumab at doses of 2 mg/kg and 10
mg/kg every 3 weeks had similar and substantial anticancer activity
and an acceptable safety profile in patients with advanced melanoma
whose disease had progressed on ipilimumab, and in those
with BRAF -mutant disease, who were previously treated with BRAF
or MEK inhibitors, or both.
• This study is the largest reported of anti-PD-1 therapy in patients with
melanoma and the first reported randomized comparison of an anti-
PD-1 agent.
30. Discussion
• Clinical benefit provided by pembrolizumab is long lasting.
• With a median follow-up of 8 months (minimum of 6 months), 88% of
responses were ongoing at the time of analysis.
• This response duration is consistent with data previously reported for
patients with pembrolizumab-treated melanoma, whereby after a
median follow-up of 15 months, 88% of responses were ongoing and
the median duration of response was not reached.
31. Discussion
• A high percentage of patients were progression free at 24 weeks.
• The finding of delayed response also suggests that additional
objective responses will occur with longer follow-up.
• According to previously reported data for a mixed population of
ipilimumab-treated and ipilimumab-naive patients, initial responses
occurred as late as 11 months after initiation of pembrolizumab, with
complete responses occurring as late as 16 months.
32. Discussion
• This prolonged time to complete response might partly explain why
the percentage of patients with complete response in this study after
a median follow-up of 8 months was only 1%.
• With additional follow-up, it is possible that there will be more
complete responses.
33. Discussion
• Previously reported data for pembrolizumab were from a
heterogeneous, non-randomized cohort in which 31% of
patients were treatment naive, 64% were ipilimumab naive,
36% received previous ipilimumab (confirmed progression not
required), and BRAF or MEK inhibitor, or both, treatment was
not required for BRAF -mutant melanoma.
• By comparison, the current randomized cohort enrolled was a
more homogeneous and heavily pretreated population because
all patients had disease that progressed on previous ipilimumab
(confirmed with two tumor assessments), 72% received at least
two previous systemic therapies, and treatment with a BRAF or
MEK inhibitor, or both, was required for all patients with BRAF -
mutant melanoma.
34. Discussion
• These factors might explain the lower percentages of patients with
complete response (1% vs 9%), any response (26% vs 41%), 24-week
PFS (37% and 45% vs 54%), and overall survival at 1 year (58% and
63% vs 81%) in the present cohort.
• It is important to note that the pattern and duration of response are
consistent with those reported previously.
• The complete response rate and ORR with pembrolizumab are also
generally consistent with those reported for nivolumab in patients
with melanoma previously treated with at least three previous doses
of ipilimumab (20% ORR, 3% complete response rate).
35. Discussion
• The safety data corroborate previously published data
showing that anti-PD-1 therapy is generally well tolerated
and safe in patients previously treated with ipilimumab,
with a safety profile similar to that reported for ipilimumab-naive
patients.
• Most drug-related adverse events in the current study were
of grade 1 or 2 severity and were reversible.
• Although uncommon, severe adverse events of potential
immune cause were successfully managed with treatment
interruption or immunosuppressive therapy, or both.
• The overall safety profile was similar in the 2 mg/kg and the
10 mg/kg groups, and no deaths due to drug-related
adverse events were reported.
36. Discussion
• There were a small number of patients with BRAF -mutant melanoma
enrolled in this study relative to the frequency of BRAF mutation
generally noted in patients with advanced melanoma.
• In the current study, previous BRAF or MEK inhibitor therapy, or both,
was required for patients with BRAF -mutant melanoma.
• Thus, it is possible that the small BRAF -mutant population enrolled is
a result of a more aggressive disease that occurs after progression on
a BRAF inhibitor, which could have led to patients not having
sufficient performance status to permit their enrolment in this study.
37. Discussion
• Generally, the response rate associated with immunotherapy in
patients with melanoma does not differ by BRAF mutation status.
• In this study, there was a trend towards a lower response in
the BRAF -mutant population.
• However, the small number of patients with BRAF mutation and BRAF
or MEK inhibitor, or both, pretreatment makes it difficult to identify
the various factors that might have contributed to response in this
important patient group.
38. Discussion
• In view of the small sample size, exploratory analysis, and overlapping
95% CIs compared with the overall and BRAF-wild type populations,
these findings should be interpreted with caution.
• Data from the ongoing, randomized, controlled KEYNOTE-002 study,
which is in progress in a similarly defined population but with a larger
sample size (n=540), are expected to be more definitive about the
activity of pembrolizumab in patients with BRAF -mutant melanoma.
39. Conclusion
• Pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every 3 weeks
could be an effective treatment option for patients with ipilimumab-refractory
advanced melanoma, a population for whom there are few
effective treatment options.