Precision Drugs Meet Payer Realities

Asked what comes to mind when they think about the oncology pipeline, attendees at the Academy of Managed Care Pharmacy (AMCP) Nexus 2026 meeting, held in San Diego October 26-29, answered with terms like expensive, overwhelming, and complicated, Kaelyn C. Boss, PharmD, did not disagree. “Overwhelming, complicated. All true,” she said.

Boss, a clinical consultant pharmacist and team lead for ForHealth Consulting at UMass Chan Medical School, kicked off the final session of the conference with Sita Bhatt, PharmD, BCOP, clinical coordinator—hematology/oncology, Boston Medical Center, Boston University, School of Medicine. Pamala A. Pawloski, PharmD, principal research scientist at the AMCP Research Institute, moderated the discussion. Boss covered breast, ovarian, gastrointestinal, bladder, skin, and benign cancers, and Batt covered non–small cell, small cell, multiple myeloma, B-cell lymphomas, acute leukemia, and transplant complications.

Three payer concerns recurred throughout the discussion, “Oncology Pipeline 2026: Advances, Trends, and Impact”: crowded markets, costs of combination regimens, and accelerated approvals that depend on confirmatory trials.¹ Global oncology spending hit $291 billion in 2025, up $39 billion in just 1 year, and is currently estimated to hit $441 billion by 2029. New agents launched in 2024 carried a median annual cost of $411,855, and cell and gene therapies, antibody-drug conjugates, and multispecific antibodies accounted for 33% of oncology trial starts in 2025.^2,3 Biosimilar and generic uptake offers some savings, Boss said, but is unlikely to offset rising costs.

The FDA has kept pace. There were 35 oncology approvals as of September 11 compared with 48 for all of 2025 and 55 for 2024. Boss noted that 9 more arrived in the 6 weeks after she gathered her data.

Breast Cancer: Switching Before Progression

The most notable shift in breast cancer has been timing. Camizestrant (Etcamah; AstraZeneca), an oral selective estrogen receptor degrader (SERD), is approved with a CDK4/6 inhibitor when an ESR1 mutation is detected during aromatase inhibitor and CDK4/6 inhibitor therapy, before the disease progresses.^1,4 Thirty percent of patients may develop the mutation. Median progression-free survival (PFS) was 16.0 months vs 9.2 months, for a 56% reduced risk of disease progression or death (HR, 0.44; 95% CI, 0.31-0.60; P < .00001).⁵

“Traditionally, we look at switching after progression,” Boss said, “but this would allow for switching before even disease progression.”

Camizestrant carries a boxed warning for arrhythmia with QTc-prolonging drugs, and its first line trial missed its primary end point.⁶ Vepdegestrant (Veppanu; Rigel Pharmaceuticals), the first oral PROteolysis-TArgeting Chimera (PROTAC) estrogen receptor degrader, is priced at parity with elacestrant and imlunestrant ($352,800/year), so these medications are likely to compete.⁷ Giredestrant, under FDA review, could become the first oral SERD in the adjuvant setting; 3-year invasive disease-free survival was 92.4% vs 89.6% with standard treatment.⁸

Gedatolisib (Revtorpyk; Celcuity), a PI3K/mTOR inhibitor, is a preferred category 1 second-line option with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative disease without a PIK3CA mutation, a group that comprises close to 60% of these patients.^9,10 The median PFS was 9.3 months with gedatolisib/fulvestrant/palbociclib vs 2.0 months with fulvestrant/palbociclib. Common trade-offs are intravenous dosing and pan-pathway toxicity, and payers must add the cost of fulvestrant/palbociclib to the $390,000 annual price of gedatolisib.¹¹

In platinum-resistant ovarian cancer, relacorilant (Lifyorli; Corcept Therapeutics) plus nab-paclitaxel had a median PFS of 6.5 months vs 5.5 months with nab-paclitaxel alone, without requiring biomarker selection.¹² At $492,700 per year plus the cost of nab-paclitaxel, uptake may be limited. Biosimilars are also on the horizon. Pertuzumab-dpzb (Poherdy; Shanghai Henlius Biologics) is expected to launch in 2028.¹³

Gastrointestinal Cancers: A First Targeted Pancreatic Option

Boss expects significant demand for daraxonrasib (Rasonque; Revolution Medicines), an oral RAS inhibitor approved in August as the first targeted therapy for metastatic pancreatic adenocarcinoma.¹⁴ Median overall survival was 13.2 months vs 6.7 months with chemotherapy. More than 2000 patients in the US received it through expanded access before its official approval; the NCCN lists it as a preferred category 1 option for subsequent therapy, and the cost is approximately $480,000/year.^15-17

“This agent is one where I’m expecting significant uptake for a number of reasons,” Boss said. “As expected, though, in the oncology space, that innovation does some with a price tag.”

Lirafugratinib, an FGFR2-selective inhibitor for cholangiocarcinoma, had a 46.5% response rate compared with 42.0% with futibatinib and 36.0% with pemigatinib, and Boss again expects competition.¹⁸ Bezuclastinib plus sunitinib extended median PFS in gastrointestinal stromal tumor from 9.2 to 16.5 months vs sunitinib alone and has the potential to become a preferred second-line option.¹⁹

Skin, Bladder, and Benign Tumors: Competition and Coverage

Among skin cancer therapies, the viral immunotherapy vusolimogene oderparepvec (Tudruqev; Replimune) had a 24.2% response rate and costs about $450,000 per 8-dose regimen for advanced, refractory melanoma.^20,21 It will likely be managed under the medical benefit because it is injected into tumors in a clinic with image guidance for deeper lesions.

In bladder cancer, intravesical cretostimogenegrenadenorepvec had a 75.5% complete response rate and a 27.9-month median duration of response in BCG-unresponsive disease, and it is entering a competitive field with a favorable toxicity profile.²² For benign tumors, pimicotinib, which is under review by the FDA for tenosynovial giant cell tumor, would be the third CSF-1R inhibitor in the class, competing with exidartinib and vimseltinib, and payers might designate a preferred agent within the class based on cost while weighing clinical factors.¹

Lung Cancer: Selectivity by Design

For Bhatt, the theme in lung cancer is “selectivity by design.” Zidesamtinib (Jideytro; GSK), a ROS1 inhibitor, had an intracranial response rate of 50% and spares tropomyosin receptor kinase, thereby reducing dizziness and ataxia.²³ At about $492,000 per year, plans may require step therapy through repotrectinib or taletrectinib.¹ These kinase inhibitors target resistance mutations and spare off-target effects.

Sevabertinib (Hyrnuo; Bayer HealthCare Pharmaceuticals), a HER2-mutant-selective inhibitor, is priced at $288,000 per year, while its competitor zongertinib costs more for patients who weight more than 90 kg.¹ Neladalkib, a fourth-generation ALK inhibitor—with a PDUFA date of November 27, 2026²⁴—is being tested against alectinib in the first line; initial use would likely be limited to later lines.

The agent with the most potential payer impact is ivonescimab, a PD-1 and VEGF bispecific antibody with a PDUFA date of November 14, 2026.²⁵ It improved PFS vs pembrolizumab, at 11.1 vs 5.8 months, in the HARMONi-2 trial (NCT05499390). Bhatt explained that most pivotal data come from China, and a global confirmatory trial is ongoing.¹

“It could be a paradigm shift,” Bhatt said, adding that studies in other cancers could broaden the eligible population considerably, “which matters for your budget forecasting.”

In small cell lung cancer, the B7-H3–directed antibody-drug conjugate ifinatamab deruxtecan was withdrawn before its October 10 action date, and Bhatt said “pulmonary monitoring is going to be essential” given its rate of interstitial lung disease.

Multiple Myeloma: A Crowded Field

Bhatt explained that cereblon E3 ligase modulators build on lenalidomide and pomalidomide by locking cereblon into its active shape more fully: roughly 10% to 20% for the older agents, 50% for iberdomide, and nearly 100% for mezigdomide.²⁶ That potency drives activity in refractory disease, along with more neutropenia.

Iberdomide (Zenbexus; Bristol Myers Squibb) plus daratumumab and dexamethasone achieved measurable residual disease (MRD)–negative complete response in 41% of patients vs 21% with daratumumab, bortezomib, and dexamethasone, but it requires a REMS program,²⁷ and grade 4 neutropenia was seen in 53.4% of patients.¹ Iberdomide’s $383,500 annual price excludes dara-dex.

Mezigdomide, with a May 13, 2027, PDUFA date,²⁸ cut the risk of progression or death by 52% and doubled PFS in the SUCCESSOR-2 trial (NCT05552976).¹ “The results that we’ve seen with it are surprising,” Bhatt said. “I do think it is going to change the market.”

Anitocabtagene autoleucel, a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy with a December 23, 2026, PDUFA date,²⁹ had a 97% overall response rate and 93% MRD negativity in the iMMagine-1 trial (NCT05396885).¹ It will compete with 2 approved CAR T products and bispecific antibodies, and the choice among them rests on cross-trial comparisons, Bhatt said. Ciltacabtagene autoleucel (Carvykti; Janssen) may offer deeper, longer responses, she added, while idecabtagene vicleucel (Abecma; Bristol Myers Quibb) may have a more favorable short-term safety profile.

Lymphoma, Leukemia, and Transplant: New Options, Open Questions

Tirabrutinib, a central nervous system (CNS)–penetrant Bruton tyrosine kinase inhibitor with a December 18 PDUFA date,³⁰ had a 64% response rate in relapsed or refractory primary CNS lymphoma, which has no FDA-approved therapy.¹ With almost no competition, Bhatt said, “We can expect it to become the default option if the [IGNITE and JCOG2314 ReSTART trials] pan out.”

REFERENCES

Sonrotoclax (Beqalzi; BeOne Medicines) is a next-generation BCL2 inhibitor for relapsed or refractory mantle cell lymphoma, with a 52% response rate against a historical 30% and activity in TP53-mutated disease.¹ In acute myeloid leukemia (AML), menin inhibitors are differentiating on resistance coverage. Ziftomenib (Komzifti; Kyowa Kirin) is for relapsed/refractory AML with a susceptible NPM1 mutation, and bleximenib for KMT2A-rearranged, NPM1-mutated acute leukemia, in phase 3 investigations, avoids a residue linked to resistance mutations, supporting a possible role after a first-generation agent.^1,31

The regulatory T-cell therapy Tregzi (Orca-T; Orca Biosystems) improved chronic graft-vs-host disease-free survival, but no randomized trial has so far compared it with posttransplantcyclophosphamide.^32,33 Plans may incorporate it into bundled payments or consider restricting it to high-risk patients, Bhatt explained. For blastic plasmacytoid dendritic cell neoplasm, pivekimabsunirine-pvzy (Decnupaz; AbbVie) costs just over $3.1 million per year for a patient who weighs 70 kg but carries a boxed warning for hepatotoxicity and venoocclusivedisease.¹