Moving Ahead In Cancer Care: 2016 ASCO Annual Meeting

Some 30,000 professionals from around the world will attend the 2016 ASCO Annual Meeting in Chicago, IL. The theme of the meeting is Collective Wisdom: The Future of Patient-Centered Care and Research.

Five studies selected from the 5,200 abstracts submitted to ASCO were featured at a pre-meeting press cast. The topics covered by these abstracts included the:

  • Impact of tumor site on treatment for metastatic colorectal cancer
  • Long-term follow-up of immunotherapy for melanoma
  • Precision medicine based on grouping patients according to biomarkers rather than tumor type
  • Family caregiver outcomes
  • Whether upfront stem cell transplant is superior to induction therapy with novel agents in multiple myeloma

Treatment for Metastatic Colorectal Cancer

A retrospective analysis of the phase 3 CALGB/SWOG 80405 (Alliance trial) showed that colorectal cancer tumors arising in the right side of the colon (cecum and ascending colon) behave differently than those that arise from the left side (the descending colon, sigmoid colon, and rectum).

These differences have treatment implications.

Patients whose primary tumors that arise on the left side have significantly improved survival compared with right-sided primary tumors (the cecum and ascending colon): median overall survival (OS) was 33.3 months vs 19.4 months, respectively. This analysis was based on tumors with wild-type KRAS.

“While previous studies had suggested that tumor location may impact colorectal cancer outcomes, the effect we observed in this analysis appears to be far greater than we expected. These findings will likely change the way we approach colorectal cancer treatment and research, even as we seek to understand the biology driving the differences in outcomes between right- and left-sided tumors,” said lead author Alan Venook, MD, University of California, San Francisco.

An exploratory analysis suggested that OS and PFS were prolonged with cetuximab and with bevacizumab in left-sided tumors. For patients treated with cetuximab, median OS was 36 months for left-sided tumors vs 16.7 months for right-sided tumors; for those who received bevacizumab, median OS was 31.4 months and 24.2 months, respectively.

Delving more deeply into this exploratory analysis, bevacizumab was associated with longer survival for right-sided patients (24.2 months vs 16.7 months, respectively), while cetuximab was associated with somewhat longer survival among patients with left-sided tumors (36 months vs 31.4 months, respectively).

“These data suggest that right-sided tumors get no benefit from cetuximab. Colorectal cancer on the right side of the colon should be treated differently those on the left side. The data suggest that bevacizumab should be included in first-line treatment for metastatic colorectal cancer patients with right-sided primary tumors regardless of KRAS status,” said Dr. Venook.

Pembrolizumab in Advanced Melanoma

Pembrolizumab achieved encouraging survival in patients with advanced melanoma who were pretreated with ipilimumab as well as those who were not, according to results of the phase 1b KEYNOTE-001 trial.

At 36 months, 40% of patients treated with pembrolizumab were alive.

Three different schedules of pembrolizumab were used in the study:

  • 24-month OS ranged from 49% to 52%
  • 36-month OS ranged from 38% to 43%
  • Best results were observed with pembrolizumab 10 mg/kg every 2 weeks, which was deemed the optimal dose by the investigators

Ninety-one study patients (15%) experienced complete remissions (CR), according to immune-response criteria, and of these, 97% are still in remission. Of these, 61 (64%) went off treatment after a median duration of 23.4 months; only 2 have had disease progression. One of the 2 has been re-started on pembrolizumab, but it is too early to evaluate response.

Median OS was 24.4 months, which is double that for advanced melanoma prior to the introduction of ipilimumab.

“Advanced melanoma is still a very challenging cancer, which it is why it is so remarkable that such a large proportion of patients see a long-term benefit from this therapy. These data confirm the use of pembrolizumab as one of the new standards of care in patients with advanced melanoma regardless of prior treatment,” stated Caroline Robert, MD, PhD, Head of the Dermatology Unit at the Institut Gustave-Roussy, Paris, France.

“These data are incredibly exciting and are the longest follow-up of an anti-PD-1 agent,” said Don Dizon, MD, ASCO spokesperson. “We see response and durable response, and this could represent a potential cure.”

Biomarker-Based Selection of Patients

A meta-analysis that included 346 phase 1 published trials of single agents involving more than 13,000 patients compared studies that used a biomarker-based selection strategy versus those that did not. The studies were published between 2011 and 2013.

The studies that employed a biomarker-based strategy had significantly improved tumor shrinkage rates: 30.6% vs 4.9%, respectively (P<.0001) and improved median PFS (5.7 months vs 2.95 months, respectively (P=.0002).

A personalized strategy was an independent predictor of improved RR and PFS. In a sub-analysis within targeted arms of these trials, studies that were not guided by biomarker-driven selection criteria had negligible RR.

A sub-analysis of 57 trials of therapies targeted to specific genes or proteins showed that treatment arms based on biomarker selection had tumor shrinkage rates of 31.1% compared with 5.1% for those that did not.

Additionally, matching patients to therapy based on genomic biomarkers achieved higher tumor shrinkage rates compared with protein biomarkers: 42% compared with 22.4%, respectively.

Lead author Maria Clemence Schwaederle, PharmD, Center for Personalized Cancer Therapy and Division of Hematology, University of California, San Diego, said: “Our study suggests that with a precision medicine approach, we can use a patient’s individual tumor biomarkers to determine whether that patient is likely to benefit from a particular therapy, even when therapy is at the earliest stage of clinical development.”

“Targeted therapies by themselves are not effective. They need to be given to the right patient,” she noted. “These were highly refractory patients,” she added.

Results suggest that phase 1 studies, which usually focus on safety, can provide important insights into optimal treatment selection. The author suggested incorporating survival endpoints into phase 1 trials.

“This is a large dataset of more than 13,000 patients. It shows the importance of precision medicine, and that using the genomic and protein biomarkers from the patient’s own tumors improves outcomes compared to approaches used in the past,” said Dr. Dizon.

Family Caregiver Outcomes

Patient-reported outcomes in clinical trials have received increased attention over the past few years. A new study looked at outcomes among family caregivers (FC) of patients with incurable lung and gastrointestinal cancers.

The study found that early integration of palliative care along with oncology care improved depression and aspects of quality of life in FC, including vitality and social functioning.

The study enrolled 350 patients and 275 potentially eligible FC: 137 patients were randomized to an intervention that included at least monthly patient visits with integrated palliative care (FC were not required to attend these visits, although 50% did) and 138 in the control group.

“This work demonstrates that the benefits of early, integrated palliative care models in oncology care extend beyond patient outcomes and positively impact the experience of family caregivers,” said lead author Areej El-Jawahri, MD, Massachusetts General Hospital, Boston, MA.

“Incorporating early palliative care creates a powerful feedback loop in families facing cancer and may make it easier for caregivers to care for their loved ones.”

Transplant for Multiple Myeloma in Era of Modern Therapy

The availability of potent novel therapies for multiple myeloma raises the question of whether autologous stem cell transplant (ASCT) should remain the standard of care for upfront treatment in patients younger than age 65.

An international, multicenter, randomized phase 3 study looked at this question by comparing ASCT versus chemotherapy using novel agents, and found that ASCT should still be considered standard of care for younger newly diagnosed patients.

The first stage of the study compared 4 cycles of bortezomib-melphalan-prednisone (VMP) versus high-dose melphalan (HDM) and single or double ASCT as intensification therapy following induction therapy with bortezomib-cyclophosphamide-dexamethasone and subsequent collection of peripheral blood stem cells.

Results of the first prespecified interim analysis included 1,266 patients who were randomized in a 1:1 ratio to VMP or HDM plus single or tandem ASCT. At 24 months, superior PFS was reported in those randomized to the transplant arm (P=.010), with a benefit across all prespecified subgroups, including high-risk cytogenetics.

A second stage randomized patients in both groups to consolidation therapy with bortezomib/lenalidomid/dexamethasone or no consolidation therapy. Analysis of this stage was not reported at the press cast.

Among patients who had not yet experienced disease progression, those randomized to ASCT had a 24% lower risk of disease progression at any future time point compared with those who did not receive transplant.

In patients with advanced disease, ASCT conferred a 48% lower likelihood of disease progression compared with the VMP group, and those with high-risk cytogenetics, ASCT was associated with a 28% lower risk of progression at any future time compared with the group that did not have transplant.

Additionally, higher rates of very good partial response (VGPR) were observed with the transplant arm: 84% versus 74% for VMP (P<.0001). A Cox regression analysis found that randomization to HDM plus ASCT was an independent predictor of prolonged PFS. Overall survival data are not yet mature, with no apparent difference between the two treatment arms.

“This study shows the superiority of upfront ASCT versus chemotherapy alone in newly diagnosed fit patients. This is further supported by the significant improvement in the rate of VGPR or higher quality response.

“Upfront ASCT still remains the preferred treatment for younger newly diagnosed multiple myeloma patients, even in the novel agent era. Further follow-up of the study is needed,” said lead author Michele Cavo, MD, Head of the Seragnoli Institute of Hematology at the University of Bologna, Italy.

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