Advances in cancer treatment have led to a growing number of survivors. At least 40% of those survivors live with chronic pain and need pain control medication. This coincides with an epidemic of opioid misuse and overdose deaths, resulting in restrictive practices that can impact patients who experience severe pain. Oncologists and other healthcare professionals who treat patients with cancer need to balance considerations of opioid misuse with effective pain control and become better educated about risk factors and management of opioids in cancer survivors.
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Anthony J. Olszanski
According to Dr. Anthony J. Olszanski, the most significant updates to the treatment of cutaneous melanoma include the recently published results of MSLT-II, which demonstrated that ultrasound-guided follow-up can be performed rather than a complete lymph node dissection, improving morbidity in patients with sentinel node metastases while not adversely affecting survival. In the adjuvant setting, the PD-1 inhibitors nivolumab and pembrolizumab are now FDA-approved, in addition to dabrafenib and trametinib, for patients with BRAF mutations.
Featured Updates to the NCCN Guidelines
Patrick A. Brown, Matthew Wieduwilt, Aaron Logan, Daniel J. DeAngelo, Eunice S. Wang, Amir Fathi, Ryan D. Cassaday, Mark Litzow, Anjali Advani, Patricia Aoun, Bhavana Bhatnagar, Michael W. Boyer, Teresa Bryan, Patrick W. Burke, Peter F. Coccia, Steven E. Coutre, Nitin Jain, Suzanne Kirby, Arthur Liu, Stephanie Massaro, Ryan J. Mattison, Olalekan Oluwole, Nikolaos Papadantonakis, Jae Park, Jeffrey E. Rubnitz, Geoffrey L. Uy, Kristina M. Gregory, Ndiya Ogba and Bijal Shah
Survival outcomes for older adults with acute lymphoblastic leukemia (ALL) are poor and optimal management is challenging due to higher-risk leukemia genetics, comorbidities, and lower tolerance to intensive therapy. A critical understanding of these factors guides the selection of frontline therapies and subsequent treatment strategies. In addition, there have been recent developments in minimal/measurable residual disease (MRD) testing and blinatumomab use in the context of MRD-positive disease after therapy. These NCCN Guidelines Insights discuss recent updates to the NCCN Guidelines for ALL regarding upfront therapy in older adults and MRD monitoring/testing in response to ALL treatment.
Melinda L. Telli, William J. Gradishar and John H. Ward
Advances in molecular testing have ushered in the new era of precision medicine. The 2018 publication of the TAILORx trial helped refine the use of genetic expression assays, specifically the 21-gene recurrence score, in assigning patients to endocrine therapy alone or with chemotherapy. The NCCN Guidelines for Breast Cancer explore the clinical applications of this study. The algorithm for managing the axilla in early breast cancer has been further refined, based on the presence or absence of clinical evidence of lymph node involvement. Ovarian suppression has been validated as the optimal approach in higher risk premenopausal women, based on updated analysis of the SOFT and TEXT pivotal trials. In the metastatic setting, the NCCN Guidelines further reinforce the benefit of the CDK4/6 inhibitors, extending the “preferred” recommendation to all the available agents in metastatic disease. Options in triple-negative breast cancer now include, for the first time, an immunotherapeutic agent.
Neil P. Shah
The NCCN Guidelines for Chronic Myeloid Leukemia (CML) criteria for discontinuation of tyrosine kinase inhibitor (TKI) therapy have not seen significant updates in the past year, but the current guidelines reinforce the safety of treatment discontinuation in appropriate and consenting patients with CML in the chronic phase who have achieved and maintained a deep molecular response. According to Dr. Neil Shah, who presented the current data, some clinicians are still unaware that treatment discontinuation is an option. Patients who wish to stop TKI therapy should consult with a CML specialty center to confirm that discontinuation is safe and appropriate; they also should be counseled on all potential benefits and risks of stopping therapy, including TKI withdrawal syndrome. In patients with CML who experience relapse after discontinuing TKI therapy, a second TKI discontinuation can be successful among those who regained a deep molecular response after TKI rechallenge, although experience to date with second discontinuation attempts is very limited. Second-generation TKIs have also demonstrated improvement in rates of deep molecular remission, making treatment discontinuation possible for a larger proportion of patients.
Wells A. Messersmith
In the last year, several impactful updates have been added to the NCCN Guidelines for Colorectal Cancer (CRC) for the management of metastatic disease, including additional options for BRAF-mutated advanced CRC and the inclusion of combination immunotherapy (PD-1 and CTLA-4) for deficient mismatch repair/microsatellite instability (MSI)–high advanced CRC. According to Dr. Wells A. Messersmith, targeted therapies (ie, VEGFR, EGFR, multitargeted tyrosine kinase inhibitors) play an important role in CRC management, but none of them have been successful in the adjuvant setting (although checkpoint inhibition is now being tested in MSI-high stage III CRC). Reliable predictive biomarkers for most agents are still greatly lacking, highlighting the importance of investing in CRC biomarker studies.
The NCCN Guidelines for Kidney Cancer have undergone a major shift in the risk categorization used for designating “preferred” and “other recommended” or “useful under certain circumstances” first-line treatments. In the most recent version of the guidelines, “favorable risk” is now its own risk category and “intermediate risk” and “poor risk” are combined into one category. The treatment recommendations for clear cell renal cell carcinoma are continually revised and more new options are anticipated based on encouraging results from pivotal trials. In his presentation at the NCCN 2019 Annual Conference, Dr. Jonasch described these promising findings.
Thomas W. Flaig
The treatment landscape of bladder cancer has changed rapidly over the past several years. The 2019 version of the NCCN Guidelines has integrated changes to tumor staging that reflect an updated understanding of the natural history of the disease and will affect how patients are treated. Further, 5 PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are approved for the treatment of bladder cancer. The FDA has limited use of ICIs as monotherapy in the first-line treatment of metastatic and advanced disease for patients who are platinum-ineligible or are cisplatin-ineligible with high PD-L1 expression and are candidates for ICIs. Ongoing predictive biomarker development and validation are needed in bladder cancer; the development of better biomarkers will be key in patient selections for therapy going forward.
James L. Mohler and Emmanuel S. Antonarakis
Updates to the NCCN Guidelines for Prostate Cancer include further refinements in taking a family history, new recommendations for germline and somatic testing, use of androgen receptor blockers for nonmetastatic castration-resistant prostate cancer, advice regarding intermittent versus continuous androgen deprivation therapy, and consideration of whether to treat the primary tumor in men diagnosed with de novo metastatic prostate cancer.