Houranieh J

Background: Therapeutic options for men with metastatic castrate-resistant prostate cancer (mCRPC) have expanded significantly over the past 5 years with several new agents demonstrating improved survival, including 2 oral agents. Abiraterone acetate (AA), a CYP-17 androgen synthesis inhibitor, obtained initial FDA approval in 2011 for post-docetaxel (DXT) use and gained expanded approval in 2012 for pre-DXT use. Enzalutamide (ENZ), an androgen receptor signaling inhibitor, also gained FDA approval in 2012 (post-DXT) and indication was expanded in 2014 (pre-DXT).

Purpose: The objective is to provide insight into the uptake of novel therapeutics and its impact on treatment for patients with mCRPC.

Methods: For this observational study, Veterans Affairs (VA) healthcare system data (including hospitalizations, outpatient visits, and pharmacy) were used to identify male veterans who received treatment for mCRPC between fiscal years 2008 and 2014. Sequencing patterns and treatment duration were assessed. Descriptive statistics were employed.

Results: During the study period, 8,774 patients initiated advanced lines of therapy associated with mCRPC. AA, DXT, and ketoconazole (KCZ) were the most commonly used firstlines of advanced therapies (24.6%, 24.8%, 47.0%, respectively). Between 2008 and 2013, the proportion of mCRPC patients treated with first-line DXT or KCZ dropped from 98% to 38% (P < .0001) while the proportion who received first-line AA increased to 58% (P < .0001). Furthermore, among the 4,169 patients treated with AA between 2011 and 2014, the proportion treated pre-DXT increased from 32% to 80% (P < .0001). AA was also the most common second-line treatment received. Between 2012 and 2013, ENZ use was low but increased dramatically. Among patients who initiated DXT, KCZ, or AA as first-line treatment in 2011/2012, median time on initial treatment was 5.9, 9.1, 11.5 months, respectively.

Conclusions: The FDA approval of AA and ENZ had a significant impact on treatment patterns for men with mCRPC within VA and was associated with decreased use of KCZ and delayed use of chemotherapy. Further information regarding patient and disease characteristics is needed. The rapid uptake of these novel agents has significant implications for disease-related outcomes.

Background: Therapeutic options for men with metastatic castrate-resistant prostate cancer (mCRPC) have expanded significantly over the past 5 years with several new agents demonstrating improved survival, including 2 oral agents. Abiraterone acetate (AA), a CYP-17 androgen synthesis inhibitor, obtained initial FDA approval in 2011 for post-docetaxel (DXT) use and gained expanded approval in 2012 for pre-DXT use. Enzalutamide (ENZ), an androgen receptor signaling inhibitor, also gained FDA approval in 2012 (post-DXT) and indication was expanded in 2014 (pre-DXT).

Purpose: The objective is to provide insight into the uptake of novel therapeutics and its impact on treatment for patients with mCRPC.

Methods: For this observational study, Veterans Affairs (VA) healthcare system data (including hospitalizations, outpatient visits, and pharmacy) were used to identify male veterans who received treatment for mCRPC between fiscal years 2008 and 2014. Sequencing patterns and treatment duration were assessed. Descriptive statistics were employed.

Results: During the study period, 8,774 patients initiated advanced lines of therapy associated with mCRPC. AA, DXT, and ketoconazole (KCZ) were the most commonly used firstlines of advanced therapies (24.6%, 24.8%, 47.0%, respectively). Between 2008 and 2013, the proportion of mCRPC patients treated with first-line DXT or KCZ dropped from 98% to 38% (P < .0001) while the proportion who received first-line AA increased to 58% (P < .0001). Furthermore, among the 4,169 patients treated with AA between 2011 and 2014, the proportion treated pre-DXT increased from 32% to 80% (P < .0001). AA was also the most common second-line treatment received. Between 2012 and 2013, ENZ use was low but increased dramatically. Among patients who initiated DXT, KCZ, or AA as first-line treatment in 2011/2012, median time on initial treatment was 5.9, 9.1, 11.5 months, respectively.

Conclusions: The FDA approval of AA and ENZ had a significant impact on treatment patterns for men with mCRPC within VA and was associated with decreased use of KCZ and delayed use of chemotherapy. Further information regarding patient and disease characteristics is needed. The rapid uptake of these novel agents has significant implications for disease-related outcomes.

Background: Therapeutic options for men with metastatic castrate-resistant prostate cancer (mCRPC) have expanded significantly over the past 5 years with several new agents demonstrating improved survival, including 2 oral agents. Abiraterone acetate (AA), a CYP-17 androgen synthesis inhibitor, obtained initial FDA approval in 2011 for post-docetaxel (DXT) use and gained expanded approval in 2012 for pre-DXT use. Enzalutamide (ENZ), an androgen receptor signaling inhibitor, also gained FDA approval in 2012 (post-DXT) and indication was expanded in 2014 (pre-DXT).

Purpose: The objective is to provide insight into the uptake of novel therapeutics and its impact on treatment for patients with mCRPC.

Methods: For this observational study, Veterans Affairs (VA) healthcare system data (including hospitalizations, outpatient visits, and pharmacy) were used to identify male veterans who received treatment for mCRPC between fiscal years 2008 and 2014. Sequencing patterns and treatment duration were assessed. Descriptive statistics were employed.

Results: During the study period, 8,774 patients initiated advanced lines of therapy associated with mCRPC. AA, DXT, and ketoconazole (KCZ) were the most commonly used firstlines of advanced therapies (24.6%, 24.8%, 47.0%, respectively). Between 2008 and 2013, the proportion of mCRPC patients treated with first-line DXT or KCZ dropped from 98% to 38% (P < .0001) while the proportion who received first-line AA increased to 58% (P < .0001). Furthermore, among the 4,169 patients treated with AA between 2011 and 2014, the proportion treated pre-DXT increased from 32% to 80% (P < .0001). AA was also the most common second-line treatment received. Between 2012 and 2013, ENZ use was low but increased dramatically. Among patients who initiated DXT, KCZ, or AA as first-line treatment in 2011/2012, median time on initial treatment was 5.9, 9.1, 11.5 months, respectively.

Conclusions: The FDA approval of AA and ENZ had a significant impact on treatment patterns for men with mCRPC within VA and was associated with decreased use of KCZ and delayed use of chemotherapy. Further information regarding patient and disease characteristics is needed. The rapid uptake of these novel agents has significant implications for disease-related outcomes.

In contrast to traditional chemotherapy, patients responding to biological or targeted therapies often are treated indefinitely until progression or toxicity. This therapeutic model, however, increases treatment costs, may induce greater toxicity and theoretically could select for earlier emergence of drug resistance. Moreover, little data are available regarding the outcomes of patients who discontinue targeted therapies after achieving remission. In this regard, we report 2 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who chose to stop therapy unrelated to toxicity or disease status after the induction of remission by the BTK inhibitor ibrutinib.

Patient A started ibrutinib for progressive CLL at an absolute lymphocyte count (ALC) of 137,000 mm3 and recurrent hemolytic anemia. After 5 months, the hemolysis had resolved (Hgb 15.6 g/dL), while the ALC had declined to 9,200 mm3. Treatment was then interrupted due to patient preference. One month after drug discontinuation, the ALC was in the normal range at 1,400 mm3 and remained within or near the normal range for a total of 12 months. Two months later, the ALC was again markedly elevated at 68,000 mm3 and anemia recurred. The patient then agreed to restart ibrutinib. After 4 months of re-treatment, he has had prompt resolution of the anemia and achieved a partial remission thus far.

Patient B was started on ibrutinib for a rising ALC (26,000 mm3) and severe hemolytic anemia. After 9 months of treatment, the hemoglobin was 13 g/dL and the ALC was in the normal range at 3,300 mm3. Due to unrelated medical problems, ibrutinib therapy was stopped. Currently, 6 months since drug discontinuation, the ALC remains in the normal range, and no other signs of CLL are present.

These clinical observations suggest that interruption of ibrutinib may be feasible in at least some CLL patients who achieve remission. Even if flow cytometry were performed at monthly intervals to detect early recurrence and ensure prompt re-institution of therapy, the cost savings would still be considerable. Of course, clinical trials will be necessary to confirm equivalent long-term efficacy and overall survival for intermittent versus continuous ibrutinib therapy in CLL.

In contrast to traditional chemotherapy, patients responding to biological or targeted therapies often are treated indefinitely until progression or toxicity. This therapeutic model, however, increases treatment costs, may induce greater toxicity and theoretically could select for earlier emergence of drug resistance. Moreover, little data are available regarding the outcomes of patients who discontinue targeted therapies after achieving remission. In this regard, we report 2 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who chose to stop therapy unrelated to toxicity or disease status after the induction of remission by the BTK inhibitor ibrutinib.

Patient A started ibrutinib for progressive CLL at an absolute lymphocyte count (ALC) of 137,000 mm3 and recurrent hemolytic anemia. After 5 months, the hemolysis had resolved (Hgb 15.6 g/dL), while the ALC had declined to 9,200 mm3. Treatment was then interrupted due to patient preference. One month after drug discontinuation, the ALC was in the normal range at 1,400 mm3 and remained within or near the normal range for a total of 12 months. Two months later, the ALC was again markedly elevated at 68,000 mm3 and anemia recurred. The patient then agreed to restart ibrutinib. After 4 months of re-treatment, he has had prompt resolution of the anemia and achieved a partial remission thus far.

Patient B was started on ibrutinib for a rising ALC (26,000 mm3) and severe hemolytic anemia. After 9 months of treatment, the hemoglobin was 13 g/dL and the ALC was in the normal range at 3,300 mm3. Due to unrelated medical problems, ibrutinib therapy was stopped. Currently, 6 months since drug discontinuation, the ALC remains in the normal range, and no other signs of CLL are present.

These clinical observations suggest that interruption of ibrutinib may be feasible in at least some CLL patients who achieve remission. Even if flow cytometry were performed at monthly intervals to detect early recurrence and ensure prompt re-institution of therapy, the cost savings would still be considerable. Of course, clinical trials will be necessary to confirm equivalent long-term efficacy and overall survival for intermittent versus continuous ibrutinib therapy in CLL.

In contrast to traditional chemotherapy, patients responding to biological or targeted therapies often are treated indefinitely until progression or toxicity. This therapeutic model, however, increases treatment costs, may induce greater toxicity and theoretically could select for earlier emergence of drug resistance. Moreover, little data are available regarding the outcomes of patients who discontinue targeted therapies after achieving remission. In this regard, we report 2 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who chose to stop therapy unrelated to toxicity or disease status after the induction of remission by the BTK inhibitor ibrutinib.

Patient A started ibrutinib for progressive CLL at an absolute lymphocyte count (ALC) of 137,000 mm3 and recurrent hemolytic anemia. After 5 months, the hemolysis had resolved (Hgb 15.6 g/dL), while the ALC had declined to 9,200 mm3. Treatment was then interrupted due to patient preference. One month after drug discontinuation, the ALC was in the normal range at 1,400 mm3 and remained within or near the normal range for a total of 12 months. Two months later, the ALC was again markedly elevated at 68,000 mm3 and anemia recurred. The patient then agreed to restart ibrutinib. After 4 months of re-treatment, he has had prompt resolution of the anemia and achieved a partial remission thus far.

Patient B was started on ibrutinib for a rising ALC (26,000 mm3) and severe hemolytic anemia. After 9 months of treatment, the hemoglobin was 13 g/dL and the ALC was in the normal range at 3,300 mm3. Due to unrelated medical problems, ibrutinib therapy was stopped. Currently, 6 months since drug discontinuation, the ALC remains in the normal range, and no other signs of CLL are present.

These clinical observations suggest that interruption of ibrutinib may be feasible in at least some CLL patients who achieve remission. Even if flow cytometry were performed at monthly intervals to detect early recurrence and ensure prompt re-institution of therapy, the cost savings would still be considerable. Of course, clinical trials will be necessary to confirm equivalent long-term efficacy and overall survival for intermittent versus continuous ibrutinib therapy in CLL.