FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA-Mutated Metastatic Castrate-Resistant Prostate Cancer.

The U.S. Food and Drug Administration (FDA) granted accelerated approval to rucaparib in May 2020 for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castrate-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane. This approval was based on data from the ongoing multicenter, open-label single-arm trial TRITON2. The primary endpoint, confirmed objective response rate, in the 62 patients who met the above criteria, was 44% (95% confidence interval [CI]: 31%-57%). The median duration of response was not estimable (95% CI: 6.4 to not estimable). Fifty-six percent of patients had a response duration of >6 months and 15% >12 months. The safety profile of rucaparib was generally consistent with that of the class of poly-(ADP-ribose) polymerase enzyme inhibitors and other trials of rucaparib in the treatment of ovarian cancer. Deaths due to adverse events (AEs) occurred in 1.7% of patients, and 8% discontinued rucaparib because of an AE. Grade 3-4 AEs occurred in 59% of patients. No patients with prostate cancer developed myelodysplastic syndrome or acute myeloid leukemia. The trial TRITON3 in patients with mCRPC is ongoing and is planned to verify the clinical benefit of rucaparib in mCRPC. This article summarizes the FDA thought process and data supporting this accelerated approval. IMPLICATIONS FOR PRACTICE: The accelerated approval of rucaparib for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castrate-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane represents the first approved therapy for this selected patient population. This approval was based on a single-arm trial demonstrating a confirmed objective response rate greater than that of available therapy with a favorable duration of response and an acceptable toxicity profile. The ongoing trial TRITON3 is verifying the clinical benefit of this drug.

Self-assessment of communication skills preparedness: adult versus pediatric skills.

PURPOSE: To characterize and compare incoming residents' self-reported 1) amount and sufficiency of medical school training in clinical communication for patients of different ages, and 2) training experience and anticipated comfort level when breaking news of serious diagnoses with patients of different ages. METHOD: A self-assessment tool was voluntarily completed by residents entering Brown- and Dartmouth-affiliated residencies. Descriptive statistics were generated and 2-tailed t tests were used to compare mean responses for patient age categories within each area of questioning. RESULTS: A total of 143 (78%) of 184 residents completed self-assessments. Estimates of training time with adult patients were greater than any other patient age category and were rated most sufficient. Twelve percent and 11% of respondents reported no formal training in pediatric and adolescent skills, respectively, and more than half reported that they had never observed a pediatric or adolescent "bad news" interaction. Half of the respondents had personally informed a patient or family of a serious diagnosis, most often concerning middle-aged or elderly patients. Respondents anticipated greatest discomfort discussing serious illness in younger patients and least discomfort discussing serious illness in adult and elderly patients. CONCLUSIONS: Residents feel less prepared for and receive less training in general communication skills, particularly skills required for delivering bad news, in pediatric clinical interactions as compared with interactions with adult patients. Additional formalized training in communication skills and strategies for breaking bad news to pediatric and adolescent patients may be warranted.

Teaching the testicular exam: a model curriculum from "A" to "Zack".

BACKGROUND AND OBJECTIVES: The testicular exam was not explicitly taught at our medical schools before 2002. In this article, we explore different phases of curriculum development, implementation, and evaluation of a method for teaching the testicular exam. METHODS: Medical students participated in surveys and focus groups, and male patients participated in focus groups. From the results of the focus groups, we developed a comprehensive testicular exam module that includes (1) a PowerPoint lecture, (2) a video, (3) reading materials, and (4) an artificial male model ("Zack"). These materials were then incorporated into family medicine clerkships. Students and faculty have evaluated the project. RESULTS: Initially, students expressed discomfort discussing sexual issues with patients, especially those of the opposite gender, and knew little about testicular cancer. Male patients had limited knowledge of the testicular self-exam and felt that their physical exam training had not been ideal. Faculty and students agreed that a lecture on the testicular exam and practice with Zack were useful in improving their exam skills, while the video and readings were less so. CONCLUSIONS: To address curricular deficits, a self-contained module on the testicular exam has been successfully incorporated into family medicine clerkships at two different medical schools. This module is easily adaptable to other settings and institutions.

Infant gender differences regarding acute established pain.

The purpose of this study was to ascertain if any gender differences existed in the behaviors of infants experiencing different levels of acute established pain and different levels of arousal within each level of pain. To do this, the behaviors of 152 two-week- to 12-month-old infants were videotaped and compared. Levels of pain were assessed by a panel of expert pediatric nurses. Results indicated that female 2-week- to 6-month-old infants performed more generally broadcast crying than did males and that the cries of female 7- to 12-month-old infants were of higher pitch than those of males. There was no gender difference in any facial or other bodily behavior. One cannot interpolate from these results that there are any gender differences in pain thresholds, only that there seem to be gender differences in behavioral responses to acute established pain.

Confounding factors in infant pain assessment during recovery from anesthesia.

ISSUES AND PURPOSE: To investigate in what ways infant pain assessments differed between outpatient surgical recovery areas (OPSRA) and other clinical settings that included inpatient postsurgical recovery areas. METHODS: Using a qualitative descriptive design, 8 nurse participants working in OPSRA and 7 nurse participants working in other clinical settings were interviewed. RESULTS: The assessments of participants in the OPSRA differed from those of other participants and were confounded by effects of a short-acting anesthetic, lower expectations of pain, and several extraneous factors. PRACTICE IMPLICATIONS: Recognizing infant pain in OPSRA is complex. Nurses working in OPSRA may need to assume leadership to address issues relating to accurate identification of infant pain and alleviating extraneous factors that may influence adequate treatment of pain.

Community involvement in developing policies for genetic testing: assessing the interests and experiences of individuals affected by genetic conditions.

Because the introduction of genetic testing into clinical medicine and public health creates concerns for the welfare of individuals affected with genetic conditions, those individuals should have a role in policy decisions about testing. Mechanisms for promoting participation range from membership on advisory committees to community dialogues to surveys that provide evidence for supporting practice guidelines. Surveys can assess the attitudes and the experiences of members of an affected group and thus inform discussions about that community's concerns regarding the appropriate use of a genetic test. Results of a survey of individuals affected with inherited dwarfism show how data can be used in policy and clinical-practice contexts. Future research of affected communities' interests should be pursued so that underrepresented voices can be heard.

Men's experiences of physical exams and cancer screening tests: a qualitative study.

BACKGROUND: American men have lower overall rates of cancer screening than women. This study was designed to elicit men's health care experiences and knowledge of testicular, prostate, and colorectal cancer (CRC) screening. METHODS: Fifty-three men participated in eight physician-led semistructured focus groups in Rhode Island and New Hampshire. Four groups (ages 18-35; N = 20) discussed testicular cancer screening. Four groups of older men (ages 40-79; N = 33) discussed prostate and colorectal cancer screening. RESULTS: Men in this study prefer physicians who establish interpersonal relationships with male patients. Lack of explanations during physical exams resulted in negative experiences. Men were eager to learn more about their health, but commonly complained that they received neither appropriate cancer screening nor sufficient explanations from their physicians. When PSA screening was offered, discussion was often inadequate. Although men expressed interest in participating in the PSA decision, sole responsibility for this complex decision was seen as undesirable. These men desired more discussion and better sources of health information during medical encounters. CONCLUSIONS: Clinician attention to communication, relationship building, patient education, and consideration for patient privacy and modesty are important for the care of male patients especially with sensitive exams and topics important to men's cancer screening.

A qualitative study of communication skills for male cancer screening discussions.

BACKGROUND: Cancer screening guidelines acknowledge the need for physician-patient discussions on appropriate tests. This study examined expert clinician communication practices associated with prostate and colorectal cancer screening and testicular cancer early detection for male patients. METHODS: Recorded observation and qualitative analysis of transcripts from 38 standardized patient interactions. RESULTS: Most effective communication practices were elicited from the data and incorporated into a model for male cancer screening discussions. CONCLUSIONS: Qualitative analysis of expert clinician interactions can identify best communication practices leading to the development of a communication model used in medical student teaching.

Perceptions of genetic discrimination among at-risk relatives of colorectal cancer patients.

PURPOSE: To explore the concerns of at-risk relatives of colorectal cancer patients about genetic discrimination and their awareness of current legislative protections. METHODS: A questionnaire was sent to unaffected individuals with a family history of colorectal cancer who had enrolled in the Johns Hopkins Hereditary Colorectal Cancer Registry (N = 777). RESULTS: Of the 470 respondents, approximately half rated their level of concern about genetic discrimination as high. The majority of respondents, 79%, learned about genetic discrimination from at least one media source (television, newspapers, magazines, and radio). If they were to pursue genetic testing, respondents with a higher level of concern about genetic discrimination would be significantly more likely to pay out of pocket, use an alias, or ask for test results to be excluded from their medical record. Awareness and understanding of legislation regarding genetic discrimination was found to be minimal. CONCLUSION: Findings from this study demonstrate the negative effect of concerns about genetic discrimination on decisions about utilization of genetic services. Stronger legislative protections against genetic discrimination and increased public education through the scientific community and media sources are needed.