Lani
05-09-2013, 01:57 PM
Got info on this in my email inbox-- called 5 minute journal club-- Apparently post SABCS--I haven't had time to access yet== apparently Includes that the most recent results at that time -- past week confirming that 1 yr of herceptin is apparently better than 6mos. and two years is no better than one year
Key Papers on Adjuvant and Neoadjuvant Treatment of HER2-Positive Breast Cancer
Research To Practice
Key Papers on Adjuvant and Neoadjuvant Treatment of HER2-Positive Breast Cancer
To go directly to slides and commentary for this issue, click here.
It’s now coming up on 8 years since that warm May day in Orlando when Dr George Sledge chaired the historic ASCO session during which the very first Phase III data sets confirming the benefit of adjuvant trastuzumab (T) with chemotherapy were unveiled. In San Antonio this past December we witnessed perhaps the final meaningful remnants of that generation of landmark studies while also getting a peek at the next set of relevant issues currently being addressed in ongoing trials. So to close out this year’s SABCS highlights series we look at several of the most intriguing presentations focused on the management of early HER2-positive disease.
1. Duration of adjuvant trastuzumab: HERA and PHARE trials
During a CME symposium our group hosted on the first night of the conference, the ever-mirthful Dr Sledge was tasked with reviewing this pragmatic topic, and to get things started the first slide he showed was a beautiful photo of the earth orbiting the sun. Of course, Dr Sledge’s visual metaphor related to the conclusion that he and most investigators had come to accept following the presentations of the HERA and PHARE data sets last October at the 2012 European Society for Medical Oncology Congress in Vienna — that 1 year of adjuvant T remains the optimal duration.
Both of these studies were updated in San Antonio. HERA, presented by Dr Martine Piccart-Gebhart, provided a definitive answer that 2 years of T is not better than 1. On the other hand, the French PHARE trial attempted to build on the signal observed in the underpowered but encouraging FinHer study of 9 weeks of T and compared 6 months to 12 months. During the presentation at San Antonio I got lost in terms like “failed to prove lack of inferiority,” but just looking at the numbers, 6 months didn’t look quite as efficacious as 12, and the collective sentiment appears to be that we’ve done the right thing all along by following Dr Sledge’s orbital concept.
2. Long-term impact of adjuvant trastuzumab
In a brilliant and detailed analysis presented to the FDA in early 2005, the late NSABP statistician Dr John Bryant proposed that combining the data from 2 ongoing simultaneous adjuvant T trials (NSABP-B-31 and NCCTG-N9831) not only was feasible but also would help to obtain a quicker answer for patients, particularly as clinicians in practice grew increasingly uncomfortable holding the line at not using this relatively nontoxic agent with such a great likelihood of success. The FDA agreed with this premise, and later that year I had the pleasure of interviewing the NSABP’s Dr Edward Romond just moments after his presentation to the ASCO multitudes of this combined data set. During this memorable conversation Dr Romond’s voice was tremulous with emotion as he recounted for our audio audience the amazing history leading to that moment.
Dr Romond was again center stage in San Antonio, presenting the 10-year survival data from that landmark combined effort. The data reveal that the effects of treatment were similar regardless of ER status (this was also seen in HERA) and the survival benefit was still maintained although somewhat attenuated due to crossover to T once the data were released (20% crossover in the NSABP/NCCTG data and an unprecedented 52% in HERA). However, the profound impact of this advance can be understood from a different perspective when we consider the final numbers from this analysis of 4,046 patients: 391 vs 227 patients with distant recurrence; 381 vs 234 deaths from breast cancer; 206 vs 137 deaths among patients with ER and/or PR-positive tumors; 212 vs 149 deaths among patients with ER and PR-negative tumors.
3. The way forward? Initial evidence suggesting a potential future role for immune checkpoint inhibitors combined with anti-HER2 agents
As this first adjuvant HER2 chapter closes, others on the horizon will soon open, and when one asks investigators which current study or concept seems most promising, the first response is quite frequently the classically straightforward but immensely interesting APHINITY trial comparing adjuvant chemotherapy/T with or without the HER2 dimerization inhibitor pertuzumab. The enthusiasm for this compelling concept is partially related to prior data from the Phase II NeoSphere trial presented by Dr Luca Gianni, which demonstrated a marked increase in pathologic CRs when pertuzumab was added to chemotherapy/T in the neoadjuvant setting.
As in many contemporary neoadjuvant trials, a critical component of NeoSphere was the collection and analysis of tumor tissue, and at San Antonio Dr Gianni presented thought-provoking findings that expression of immune-based biomarkers, including PD-1, PD-L1, CTLA-4 and others, may predict benefit from HER2-directed therapies. These hypothesis-generating data may open the door to a new frontier in which anti-HER2 therapy is combined with the immune modulators that are offering so much hope in melanoma, renal cell carcinoma, lung cancer and other challenging neoplasms. It will be fascinating to compare the NeoSphere translational findings to those about to be presented with the very first oral breast cancer paper at the upcoming ASCO meeting by Dr Lisa Carey from a major CALGB neoadjuvant HER2 study that also includes extensive tissue correlates.
This concludes our annual San Antonio wrap-up. Keep an eye out for our upcoming pre-ASCO email/video program with highlights from a recent breast cancer clinical investigator Think Tank with more on these and other new data sets and trial concepts.
Neil Love, MD
Research To Practice
Miami, Florida
Would someone please attach a link?
Thanks!
Key Papers on Adjuvant and Neoadjuvant Treatment of HER2-Positive Breast Cancer
Research To Practice
Key Papers on Adjuvant and Neoadjuvant Treatment of HER2-Positive Breast Cancer
To go directly to slides and commentary for this issue, click here.
It’s now coming up on 8 years since that warm May day in Orlando when Dr George Sledge chaired the historic ASCO session during which the very first Phase III data sets confirming the benefit of adjuvant trastuzumab (T) with chemotherapy were unveiled. In San Antonio this past December we witnessed perhaps the final meaningful remnants of that generation of landmark studies while also getting a peek at the next set of relevant issues currently being addressed in ongoing trials. So to close out this year’s SABCS highlights series we look at several of the most intriguing presentations focused on the management of early HER2-positive disease.
1. Duration of adjuvant trastuzumab: HERA and PHARE trials
During a CME symposium our group hosted on the first night of the conference, the ever-mirthful Dr Sledge was tasked with reviewing this pragmatic topic, and to get things started the first slide he showed was a beautiful photo of the earth orbiting the sun. Of course, Dr Sledge’s visual metaphor related to the conclusion that he and most investigators had come to accept following the presentations of the HERA and PHARE data sets last October at the 2012 European Society for Medical Oncology Congress in Vienna — that 1 year of adjuvant T remains the optimal duration.
Both of these studies were updated in San Antonio. HERA, presented by Dr Martine Piccart-Gebhart, provided a definitive answer that 2 years of T is not better than 1. On the other hand, the French PHARE trial attempted to build on the signal observed in the underpowered but encouraging FinHer study of 9 weeks of T and compared 6 months to 12 months. During the presentation at San Antonio I got lost in terms like “failed to prove lack of inferiority,” but just looking at the numbers, 6 months didn’t look quite as efficacious as 12, and the collective sentiment appears to be that we’ve done the right thing all along by following Dr Sledge’s orbital concept.
2. Long-term impact of adjuvant trastuzumab
In a brilliant and detailed analysis presented to the FDA in early 2005, the late NSABP statistician Dr John Bryant proposed that combining the data from 2 ongoing simultaneous adjuvant T trials (NSABP-B-31 and NCCTG-N9831) not only was feasible but also would help to obtain a quicker answer for patients, particularly as clinicians in practice grew increasingly uncomfortable holding the line at not using this relatively nontoxic agent with such a great likelihood of success. The FDA agreed with this premise, and later that year I had the pleasure of interviewing the NSABP’s Dr Edward Romond just moments after his presentation to the ASCO multitudes of this combined data set. During this memorable conversation Dr Romond’s voice was tremulous with emotion as he recounted for our audio audience the amazing history leading to that moment.
Dr Romond was again center stage in San Antonio, presenting the 10-year survival data from that landmark combined effort. The data reveal that the effects of treatment were similar regardless of ER status (this was also seen in HERA) and the survival benefit was still maintained although somewhat attenuated due to crossover to T once the data were released (20% crossover in the NSABP/NCCTG data and an unprecedented 52% in HERA). However, the profound impact of this advance can be understood from a different perspective when we consider the final numbers from this analysis of 4,046 patients: 391 vs 227 patients with distant recurrence; 381 vs 234 deaths from breast cancer; 206 vs 137 deaths among patients with ER and/or PR-positive tumors; 212 vs 149 deaths among patients with ER and PR-negative tumors.
3. The way forward? Initial evidence suggesting a potential future role for immune checkpoint inhibitors combined with anti-HER2 agents
As this first adjuvant HER2 chapter closes, others on the horizon will soon open, and when one asks investigators which current study or concept seems most promising, the first response is quite frequently the classically straightforward but immensely interesting APHINITY trial comparing adjuvant chemotherapy/T with or without the HER2 dimerization inhibitor pertuzumab. The enthusiasm for this compelling concept is partially related to prior data from the Phase II NeoSphere trial presented by Dr Luca Gianni, which demonstrated a marked increase in pathologic CRs when pertuzumab was added to chemotherapy/T in the neoadjuvant setting.
As in many contemporary neoadjuvant trials, a critical component of NeoSphere was the collection and analysis of tumor tissue, and at San Antonio Dr Gianni presented thought-provoking findings that expression of immune-based biomarkers, including PD-1, PD-L1, CTLA-4 and others, may predict benefit from HER2-directed therapies. These hypothesis-generating data may open the door to a new frontier in which anti-HER2 therapy is combined with the immune modulators that are offering so much hope in melanoma, renal cell carcinoma, lung cancer and other challenging neoplasms. It will be fascinating to compare the NeoSphere translational findings to those about to be presented with the very first oral breast cancer paper at the upcoming ASCO meeting by Dr Lisa Carey from a major CALGB neoadjuvant HER2 study that also includes extensive tissue correlates.
This concludes our annual San Antonio wrap-up. Keep an eye out for our upcoming pre-ASCO email/video program with highlights from a recent breast cancer clinical investigator Think Tank with more on these and other new data sets and trial concepts.
Neil Love, MD
Research To Practice
Miami, Florida
Would someone please attach a link?
Thanks!