NCCN guideline preview: 5 upcoming changes every oncologist should know
Industry Buzz
The emergence of novel targeted therapies for NSCLC reiterates the importance of biomarker testing, particularly in patients with advanced/metastatic NSCLC, to help clinicians identify the most appropriate treatment options for patients.
—Tejas Patil, MD, to OncLive
The National Comprehensive Cancer Network (NCCN) is a key player in today’s cancer care, developing cutting-edge, evidence-based recommendations on everything from screening and diagnosis to treatment and supportive care.
Recently updated guidelines (or anticipated updates) make it clear that cancer care is shifting toward personalized, biomarker-driven treatment, where tumors are tested early, and therapies are based on specific mutations rather than a one-size-fits-all approach. Ahead: What may be changing in clinical practice.
There’s also a focus on smarter drug combinations, better sequencing, and greater attention to mental health.[] Here are some of the hottest topics today.
Non–small-cell lung cancer (NSCLC)
The 2026 NCCN updates in NSCLC show a clear shift toward targeted drugs, biomarker testing, and smarter sequencing. For example, the guidelines recommend datopotamab deruxtecan (Dato-DXd)—an antibody-drug conjugate (ADC)—as a preferred second-line treatment. Dato-DXd is also a preferred third-line treatment as well as a subsequent therapy option for patients with certain mutations.
Combination therapies are getting major attention here, too. Osimertinib plus chemotherapy, or amivantamab plus lazertinib, are recommended as top options for patients with EGFR mutations detected early.
Patients will now have the option to try combination therapy out of the gate—but that means clinicians will need to identify EGFR mutations early on.
"The emergence of novel targeted therapies for NSCLC reiterates the importance of biomarker testing, particularly in patients with advanced/metastatic NSCLC, to help clinicians identify the most appropriate treatment options for patients," Tejas Patil, MD, member of the NCCN Clinical Practice Guidelines in Oncology Panel for NSCLC, told OncLive.[]
Gastrointestinal malignancies
Gastrointestinal malignancies are seeing major updates as well—with immunotherapy and combination treatments designed to work earlier.
For example, the guidelines now recommend that in patients with rectal cancer, chemotherapy with FOLFIRINOX be used prior to surgery in certain patients (e.g., those who are mismatch repair–proficient, and who don’t respond to immunotherapy) whose cancer can still be removed and has only spread to the liver and/or lungs.
The guidelines are also now recommending that all patients with gastric cancer get PD-L1 testing early on, which can help clinicians know whether immunotherapy will be beneficial. Patients who are PD-L1 negative tend to be less responsive to immunotherapy. Once again, testing early guides the treatment approach.
Multiple myeloma
Treatment options for multiple myeloma (MM) are broadening and getting more aggressive, with a focus on combination therapies. In patients under 80 who will not be receiving a hematopoietic stem cell transplant (HSCT), daratumumab plus bortezomib, lenalidomide, and dexamethasone was added as a preferred regimen.
Newer treatments such as CAR T-cell therapies and bispecific antibodies are now recommended for MM. For example, linvoseltamab, a bispecific antibody immunotherapy drug, was added as an option for patients with pretreated disease after four lines of therapy.
Additionally, idecabtagene vicleucel (ide‐cel) and ciltacabtagene autoleucel (cilta‐cel) are emerging CAR‐T therapies for patients with relapsed/refractory MM.[]
Breast cancer
This year’s NCCN’s guidelines are all about targeting specific mutations in breast cancer.
A notable guideline update recommends imlunestrant, a selective estrogen receptor degrader (SERD) approved in 2025 for first- or later-line therapy for recurrent unresectable or stage IV hormone receptor (HR)-positive, HER2-negative disease with an ESR1 mutation.
Another example: Erdafitinib was recommended as “useful in certain circumstances” for patients with stage IV (M1) disease with FGFR1, FGFR2, or FGFR3 fusions or mutations.
Mental health
Beyond the physical, new NCCN guidelines also tackle the mental health effects of dealing with cancer that patients experience.
The guidelines recommend that providers offer cancer-related distress (CRD) screenings and treatment to every patient. The new guidelines also remove words like “problem” in referring to CRD, and replace them with more neutral words like “concern.”
The intention behind the revised language is to encourage patients to share their psychosocial difficulties more openly, as this can support accurate assessment and facilitate referral to neuropsychology, occupational therapy, or rehabilitation services.[] []
Related: ADCs in practice: How new approvals are changing cancer care