Health & Medical

Tweaking Repairs Alternate ideas in Metastatic CRC

Two maintenance solutions for metastatic colorectal most cancers (CRC) reduced the risk of illness progression or loss of life following first-line chemotherapy, a pair of randomized trials from Europe stumbled on.

In the German PANAMA appreciate, alongside with panitumumab (Vectibix) to maintenance therapy with 5-fluorouracil (5-FU) plus leucovorin improved median progression-free survival (PFS) from 5.7 months to 8.8 months in sufferers with RAS wild-kind illness (HR 0.72, 80% CI 0.60-0.85, P=0.014), reported Dominik Paul Modest, MD, of the University Effectively being facility of Munich.

“The combination of 5-FU-leucovorin plus panitumumab would possibly per chance well level-headed be belief to be a preferred option of maintenance therapy following FOLFOX/panitumumab in sufferers with RAS wild-kind metastatic colorectal most cancers,” Modest concluded.

In the meantime, median PFS within the FOCUS4-N trial prolonged from 1.9 months with active monitoring to three.8 months with capecitabine maintenance amongst a neighborhood of sufferers without targetable tumor mutations (BRAF, PIK3CA, KRAS/p53), who spoke back or had precise illness following first-line chemotherapy (adjusted HR 0.38, 95% CI 0.28-0.51), constant with Richard Adams, MD, MBBS, of Cardiff University and Velindre Most cancers Centre in Wales.

“Capecitabine maintenance approach is a cheap option for a clinician to consult with their patient at the tip of their first-line induction chemotherapy — truly doubles the time until they’re going to pray to come wait on to full-dose induction usual anti-most cancers therapy,” acknowledged Adams. “FOCUS4-N lays out choices between increased toxicities and progression-free survival, which wait on and picture that dialogue.”

Findings from the 2 trials had been presented at some level of the virtual American Society of Medical Oncology (ASCO) annual meeting.

“Will these outcomes commerce our discover? I make no longer judge so,” acknowledged ASCO-invited discussant Wen Wee Ma, MBBS, of the Mayo Clinic in Rochester, Minnesota.

“I judge maintenance therapy would possibly per chance well level-headed be belief to be for sufferers who enact alter when present process induction chemotherapy,” he acknowledged. “I judge right here’s very so for those sufferers who greatest enact precise illness as simplest response at some level of induction.”

For responders to induction chemotherapy, Ma instructed that per chance much less is extra, as these sufferers seemingly have a extra favorable tumor biology, and maintenance in this neighborhood with capecitabine or 5-fluorouracil-leucovorin on my own would possibly per chance be sufficient.

“Where make we fling from right here?” he acknowledged. “If we are reading a historical previous book on maintenance therapy in metastatic colorectal most cancers, we’re seemingly at the earlier few pages. Except there are novel frontline therapeutics to be evaluated or promising predictive biomarkers, I judge it is a ways time to focal level our treasured sources onto other extra urgent questions within the self-discipline.”


The part II PANAMA trial included 377 metastatic CRC sufferers with RAS wild-kind illness who had been handled with FOLFOX plus panitumumab and had spoke back or executed precise illness. Sufferers had been then randomized 1:1 to maintenance 5-FU-leucovorin on my own or with panitumumab. PFS following maintenance therapy became the principle endpoint.

The total response rate (ORR) with maintenance therapy became enormously better within the panitumumab arm, at 40.8% when in contrast with 26% with 5-FU-leucovorin on my own (OR 1.96, 95% CI 1.14-3.36, P=0.02), alongside with full responses in 7.2% versus 4.9%, respectively.

Exploratory PFS analyses showed that most subgroups both benefited from the addition of panitumumab or liked that arm, though no income became viewed for sufferers requiring reduced doses.

Median total survival (OS) reached 28.7 months within the appreciate arm versus 25.7 months within the alter arm (HR 0.84, 95% CI 0.60-1.18, P=0.32), though Modest cautioned that with greatest 54% of OS events being recorded or no longer it is too early to design firm conclusions.

Employ of re-induction chemotherapy (with FOLFOX/panitumumab) became much less frequent within the investigational arm when in contrast with the alter arm (45 vs 75 sufferers). But interestingly, PFS and ORR following re-induction had been both a ways superior in alter-arm sufferers.

Median PFS following re-induction became 3.3 months within the panitumumab arm when in contrast with 5.8 months within the 5-FU-leucovorin-on my own arm (HR 2.62, 95% CI 1.71-4.02, P<0.001). ORRs with re-induction had been 8.9% and 34.7%, respectively (OR 0.18, 95% CI 0.06-0.57, P=0.002).

“The low frequency and moderate efficacy of re-induction following maintenance with 5-FU-leucovorin plus panitumumab suggests that induction of a novel therapy line rather than re-induction of the initial therapy regimen would possibly per chance be a extra favorable option,” acknowledged Modest.

Ma smartly-known that “a simplistic calculation” of PFS for maintenance plus re-induction with the panitumumab technique instructed a full enchancment of “precise 2 weeks.”

“It’s a ways unclear if that is clinically meaningful sufficient to imply that panitumumab would possibly per chance well level-headed be included for all RAS wild-kind sufferers at some level of maintenance therapy,” he acknowledged.

Sufferers in PANAMA had a median age of 65-66 years, two-thirds had been males, about 70% had passed thru most essential tumor resection, 80% had left-sided tumors and synchronous metastatic illness, and 43-49% had a couple of organ involved. Sufferers had been stratified by prior response, with roughly 80% having executed full or partial responses to their initial therapy and the final having precise illness as simplest response.

Harmful events (AEs) occurred extra continuously with panitumumab, the most total of which, versus 5-FU-leucovorin on my own, included pores and skin rash (26.4% vs 6.5%), stomatitis (21.6% vs 10.6%), paronychia (18.4% vs 4.9%), infections (16.8% vs 8.1%), hypomagnesemia (16.8% vs 0.8%), fatigue (16% vs 11.4%), and pores and skin fissures (14.4% vs 3.3%).

Widespread grade 3/4 AEs with panitumumab included pores and skin rash (7.2%), hypomagnesemia (6.4%), paronychia (4.8%), infections (4%), and pores and skin fissures (2.4%).


From 2014 to 2020, the trial randomized 254 sufferers who had precise illness following 16 weeks of first-line chemotherapy, in an unblinded vogue, to both active monitoring or maintenance capecitabine (1,250 mg/m2 twice day after day; 2 weeks on, then 1 week off). The most essential endpoint became PFS, with OS, safety, and quality of existence (QOL) amongst the secondary endpoints.

Certain traits — left-sided tumors, those with PIK3CA wild-kind or no PTEN loss, and no prior EGFR inhibitor exposures — looked to foretell improved PFS with the maintenance technique.

The outcomes compare favorably to the CAIRO3 appreciate of maintenance capecitabine plus bevacizumab, acknowledged Adams. He smartly-known that OS in both trials became no longer enormously improved with the maintenance approaches.

OS in FOCUS4-N reached a median 15.2 months with active monitoring and 14.8 months with maintenance capecitabine (HR 0.93, 95% CI 0.69-1.27).

Toxicities had been mostly grade 1/2, acknowledged Adams, nonetheless a ways extra frequent with the maintenance technique, with better charges of diarrhea, fatigue, nausea, and hand-foot syndrome. There had been no important QOL differences on the EQ-5D scale between the 2 palms.

  • creator['full_name']

    Ian Ingram is Managing Editor at MedPage As of late and helps duvet oncology for the positioning.


PANAMA became funded by Amgen and Arbeitsgemeinschaft Internistische Onkologie.

Modest disclosed relationships with Amgen, Bristol Myers Squibb, Lilly, Merck KGaA, Merck Sharpe & Dohme, Onkowissen, Pfizer, Pierre Fabre, Roche, Sanofi, Servier, and Taiho Oncology.

FOCUS4-N became supported by Most cancers Analysis UK.

Adams reported relationships with Amgen, AstraZeneca, Bayer, Merck Serono, Merck Fascinating & Dohme, and Servier.

Ma reported an institutional relationship with Wellstat Therapeutics, as effectively as institutional compare funding from Actuate Therapeutics, Athenex, BioMed Valley Discoveries, Bristol Myers Squibb, Ipsen, Merrimack, and Solar Pharma.

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